tbuckley/cabot-search huggingface dataset:
Platelet MAO activity in alcoholic patients and their first-degree relatives
Authors: G S Alexopoulos, K W Lieberman, R J Frances
Journal: American Journal of Psychiatry (1983)

The authors studied 49 alcoholic in patients in remission, 18 first-degree relatives of 10 of these alcoholics, and 25 normal control subjects. Alcoholic patients had significantly lower platelet monoamine oxidase (MAO) activity than control subjects. There was an inverse relationship between platelet MAO levels in the alcoholic patients and prevalence of reported alcoholism in their first-degree relatives. First-degree relatives of alcoholics had lower platelet MAO activity than control subjects. The data suggest a relationship between low platelet MAO activity and predisposition to familial alcoholism.
AB0377 Endothelial Dysfunction in Patients with Rheumatoid Arthritis Combined with Hypertension and its Correction with L-Arginine Aspartate
Authors: O. Sirenko, O. Kuryata, T. Lysunets
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Abstract</h3> Pyridox(am)ine 5'-phosphate oxidase (PNPO) is a rate-limiting enzyme in converting dietary vitamin B6 (VB6) to pyridoxal 5'-phosphate (PLP), the biologically active form of VB6, and involved in the synthesis of neuro-transmitters including GABA, dopamine, and serotonin. In humans, PNPO mutations have been increasingly identified in neonatal epileptic encephalopathy and more recently also in early-onset epilepsy. Till now, little is known about the neurobiological mechanisms underlying PNPO-deficiency-induced seizures due to the lack of animal models. Previously we identified a c.95 C &gt; A missense mutation in <i>sgll</i> - the <i>Drosophila</i> homolog of human <i>PNPO</i> (<i>hPNPO</i>) and found mutant (<i>sgll</i><sup>95</sup>) flies exhibiting a lethal phenotype on a diet devoid of VB6. Here we report the establishment of both <i>sgll</i><sup>95</sup> and ubiquitous <i>sgll</i> knockdown (KD) flies as valid animal models of PNPO-deficiency-induced epilepsy. Both <i>sgll</i><sup>95</sup> and <i>sgll</i> KD flies exhibit spontaneous seizures before they die. Electrophysiological recordings reveal that seizures caused by PNPO deficiency have characteristics similar to that in flies treated with GABA antagonist picrotoxin. Both seizures and lethality are associated with low PLP levels and can be rescued by ubiquitous expression of wild-type <i>sgll</i> or <i>hPNPO</i>, suggesting the functional conservation of the PNPO enzyme between humans and flies. Results from cell type-specific <i>sgll</i> KD further demonstrate that PNPO in the brain is necessary for seizure prevention and survival. Our establishment of the first animal model of PNPO deficiency will lead to better understanding of VB6 biology, the <i>PNPO</i> gene and its mutations discovered in patients, and can be a cost-effective system to test therapeutic strategies.
The diagnostic validity of anxiety disorders and their relationship to depressive illness
Authors: A Breier, D S Charney, G R Heninger
Journal: American Journal of Psychiatry (1985)

Several serious questions exist regarding the diagnostic classification of anxiety disorders. The authors examine the diagnostic validity of generalized anxiety disorder and panic disorder and explore their relationship to major depression, critically reviewing relevant descriptive, lifetime occurrence, family and genetic, drug treatment, and neurobiological studies. There is strong support for the diagnostic validity of panic disorder, but few data are found to support a separate diagnostic classification of generalized anxiety disorder. In addition, several lines of evidence suggest that a common vulnerability may exist for some forms of panic disorder and major depression. The implications of these findings for diagnostic application, treatment, and future research are discussed.
Clinical characteristics of patients with concurrent major depressive disorder and panic disorder
Authors: L Grunhaus, A C Pande, M B Brown, J F Greden
Journal: American Journal of Psychiatry (1994)

This study was designed to test the hypothesis that patients with both major depressive disorder and panic disorder exhibit more clinical symptoms and have a more protracted course of illness than patients with major depressive disorder only.The authors compared standardized clinical evaluations (from Schedule for Affective Disorders and Schizophrenia interviews) of 119 patients with major depressive disorder only and 57 patients with major depressive disorder and concurrent panic disorder. Clinical and demographic variables were included.The patients with both disorders reported symptoms of major depressive disorder earlier in life and also required treatment and hospital admission earlier in life. Many clinical features during the index episode were significantly more severe in the patients with both disorders. A logistic regression identified a "panic index" consisting of the symptoms of somatic anxiety, phobia, indecisiveness, and feelings of inadequacy. Scores on this index allowed proper classification of patients to either of the two diagnostic groups with high reliability.In major depressive disorder, the presence of panic disorder is suggestive of a more severe and precocious form of illness.
Clinical analysis of 670 cases in two trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group subtyped according to the Revised European-American Classification of Lymphoid Neoplasms: a comparison with the Working Formulation
Authors: S Pittaluga, L Bijnens, I Teodorovic, A Hagenbeek, JH Meerwaldt, R Somers, J Thomas, EM Noordijk, C De Wolf-Peeters
Journal: Blood (1996)
Acute gastric mucosal ischemic ulcer: a rare adverse result of peroral endoscopic myotomy
Authors: Chia-Wei Yang, Bing-Yen Wang, Kun-Ching Chou, Hsu-Heng Yen, Yang-Yuan Chen
Journal: Endoscopy (2015)

A 60-year-old man was referred complaining of dysphagia, retrosternal pain, and regurgitation after each meal over the previous 6 years, his symptoms having worsened in the previous year. He was diagnosed with achalasia following examination that included an esophagography ([Fig. 1]). We treated him by performing peroral endoscopic myotomy (POEM) [1].
Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation
Authors: A C Hurt, R T Lee, S K Leang, L Cui, Y M Deng, S P Phuah, N Caldwell, K Freeman, N Komadina, D Smith, D Speers, A Kelso, R T Lin, S Maurer-Stroh, I G Barr
Journal: Eurosurveillance (2011)

A novel influenza A(H1N1)2009 variant with mildly reduced oseltamivir and zanamivir sensitivity has been detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia during the early months of 2011. The variant, which has also been detected in other regions of the Asia-Pacific, contains a S247N neuraminidase mutation. When combined with the H275Y mutation, as detected in an oseltamivir-treated patient, the dual S247N+H275Y mutant had extremely high oseltamivir resistance.
KEYNOTE-040: A phase III randomized trial of pembrolizumab (MK-3475) versus standard treatment in patients with recurrent or metastatic head and neck cancer.
Authors: Ezra E. W. Cohen, Jean-Pascal H. Machiels, Kevin J. Harrington, Barbara Burtness, Sang Won Shin, Christine K. Gause, Ann M. Swift, Holly Brown, Andrea Marie Perrone, Jonathan D. Cheng, Ramona F. Swaby, Christophe Le Tourneau
Journal: Journal of Clinical Oncology (2015)

TPS6084 Background: Prognosis of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is poor, with limited treatment options and survival rates of 6-9 months following standard-of-care (SOC) therapies. Pembrolizumab, a humanized IgG4 monoclonal antibody against PD-1 designed to block the interaction between PD-1 and its ligands PD-L1 and PD-L2, has demonstrated clinical efficacy by investigator review (confirmed and unconfirmed responses) in a phase I study of R/M HNSCC. Preliminary PD-L1 biomarker data suggest that response rate may be greater in PD-L1–positive patients. Methods: In this global open-label, phase III KEYNOTE-040 (NCT02252042) trial, 466 subjects with recurrent or metastatic HNSCC that have failed prior platinum therapy will be randomized (1:1) to pembrolizumab (200 mg Q3W) vs investigator's choice SOC (single-agent methotrexate, docetaxel, or cetuximab). Randomization will be stratified by ECOG PS (0 vs 1), human papillomavirus (HPV) status in oropharyngeal cancer by p16 immunohistochemistry testing (positive vs negative), and centralized PD-L1 status (positive vs negative). Pembrolizumab will be given for ≤ 24 months or until disease progression, unacceptable toxicity, or investigator decision. AEs will be assessed according to NCI CTCAE, v4.0. Imaging will occur per RECIST v1.1 at 9 weeks and every 6 weeks thereafter. Modified RECIST, which allows for continued treatment after initial radiographic progression until confirmation imaging ≥ 4 weeks, will be used to account for unique responses seen with pembrolizumab. Radiographic responses will be confirmed by independent central review by RECIST v1.1 and modified RECIST and analyzed in real time for verification of progressive disease by RECIST v1.1. Survival follow-up will occur every 12 weeks. Primary end points are progression free survival (PFS) and overall survival (OS); secondary end points include ORR, DOR and PFS, OS, and ORR in PD-L1+ patients. Treatment differences in PFS and OS will be assessed using stratified log-rank test; Hazard ratios with 95% confidence intervals will be estimated using stratified Cox proportional hazard models. Clinical trial information: NCT02252042.
DNA Damage and Cytotoxicity Induced by Metabolites of Anthracycline Antibiotics, Doxorubicin and Idarubicin
Authors: E Ferrazzi, J M Woynarowski, A Arakali, D E Brenner, T A Beerman
Journal: Cancer Communications (1991)

This study assessed the ability of major metabolites of two types of anthracycline antibiotics, doxorubicin and idarubicin (4-demethoxydaunorubicin) to damage DNA in mouse fibrosarcoma 935.1 cells. Since DNA lesions by anthracyclines may be mediated by topoisomerase II, we also characterized the ability of the drugs to inhibit this enzyme. The C-13 alcohol and aglycone metabolites of doxorubicin and idarubicin were compared to the parent drugs in terms of induction of DNA single strand breaks measured by filter elution. In whole cells, the maximal DNA strand breakage induced by the C-13 alcohol metabolites was similar to that of their respective parent drugs. In isolated nuclei, however, the alcohol metabolites were two times more potent than the parent drugs. The aglycone metabolites produced very little damage in either whole cells or nuclei. The doxorubicin compounds differed markedly from idarubicin drugs in the way their ability to induce DNA breaks was related to cytotoxic activity. Doxorubicin and doxorubicinol cytotoxic effects (50% cell growth inhibition at 0.2 and 4 microM, respectively) coincided (in terms of drug concentrations) with the induction of significant breakage of cellular DNA. In contrast, the concentrations of idarubicin and idarubicinol needed to produce 50% growth inhibition (0.005 and 0.006 microM, respectively) were about 20 times lower than drug levels that induced significant DNA damage. All six compounds inhibited the catalytic activity of isolated topoisomerase II. While the alcohol metabolites produced this inhibition at concentrations similar to those of their parent drugs (5-10 microM), the aglycones were again much less active.(ABSTRACT TRUNCATED AT 250 WORDS)
PTH-123 Urinary volatile organic compounds as a biomarker for hepatocellular carcinoma (HCC)
Authors: A Bond, R Aggio, P Johnson, S Berhane, C Probert
Journal: Gut (2015)

<h3>Introduction</h3> Primary liver cancer is the third largest contributor to cancer mortality in the world, with more than half a million people worldwide diagnosed each year. Over the last 3 decades the incidence and mortality of HCC has been steadily increasing. The major factors contributing to survival are the degree of the underlying liver disease and the size of the tumour at diagnosis. Therefore early diagnosis is vital to improve outcomes. Volatile organic compounds (VOCs) have been investigated as biomarkers of a range of disorders. We report the first pilot study of urinary VOCs as biomarkers for HCC. <h3>Method</h3> A 400 ul urine sample was collected from 60 patients with a confirmed diagnosis of cirrhosis: 33 patients without and 27 patients with HCC. Urine samples were subsequently freeze-dried and analysed by Gas Chromatography – Mass Spectrometry. VOCs were identified and quantified using an in-house pipeline involving the Automated Mass Spectral Deconvolution and Identification System (AMDIS), the NIST mass spectral library and the R package Metab. Statistical analyses were performed using the R software and the web-tool Metaboanalyst. <h3>Results</h3> A total of 118 VOCs were identified across all samples. There were significantly higher number of VOCs identified in the cirrhotics without HCC compared to those with HCC (<i>t</i>-test, <i>p-value = 0.034</i>). Categorical comparison for prevalence demonstrated methanethiol to be less prevalent VOC in those with HCC (<i>t</i>-test, <i>p-value = 0.0083</i>). Comparison of VOCs abundances reported methanethiol at significantly higher levels in patients without HCC (<i>t</i>-test, <i>p-value = 0.0088</i>) (Figure 1). PLS-DA of those with HCC showed great separation between those with alcohol and viral hepatitis as the underlying aetiology. A supporting vector machine (SVM) model was then developed using methanethiol and additional selected features of qualitative data. After validation using a repeated 10 fold cross validation scheme, the SVM model returned a mean accuracy of 80% for the diagnosis of HCC. <h3>Conclusion</h3> The results presented here are in agreement with the literature. In particular, the decrease of methanethiol appears to have the most promise as a biomarker for the development of HCC. The model developed here showed great accuracy in classifying urine samples from patients with HCC, which indicates a great potential of VOCs as diagnosis or screening tool. A larger study would be required to investigate it further. <h3>Disclosure of interest</h3> None Declared.
Acute psychosis, increased water ingestion, and inappropriate antidiuretic hormone secretion
Authors: M A Raskind, H Orenstein, T G Christopher
Journal: American Journal of Psychiatry (1975)

The authors describe three postmenopausal women with agitated psychotic depression, increased water ingestion, and electrolyte values consistent with the syndrome of inappropriate antidiuretic hormone (ADH) secretion. They hypothesize that this clinical triad represents a syndrome reflecting underlying dysfunction of the hypothalamus and limbic system of the brain. The diagnosis of inappropriate ADH in one of the patients was directly confirmed by a recently developed serum radioimmunoassay.
AB0160 HDL Subclasses Concentration and Size Are Smaller in Systemic Lupus Erythematosus (SLE) and Are Not Modified During Sle Clinical Flares
Authors: A. Nuria, S. Parra, M. Heras, N. Canela, A. Castro, X. Correig
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> A growing body of evidences reinforces the close link between systemic lupus erythematosus (SLE) and atherosclerosis which is due to traditional and non-traditional risk factors for cardiovascular diseases (CVD) that are overrepresented in SLE patients. Some studies have described a particular pattern of dyslipoproteinemia characterized by low HDL levels and increased triglycerides in SLE patients. <h3>Objectives</h3> The aim of this study is to further characterize the HDL fraction of SLE and control patients, and to investigate whether the concentration and size of the main three HDL subclasses (large, medium and small HDL) of SLE patients are modified in a clinical flare. <h3>Methods</h3> We studied a cohort of thirteen women with SLE and 13 age-matched population-based control women. (Lipids and apolipoprotein where measured using enzymatic and immunoturbidimetric assays. Total HDL was isolated from plasma using a sequential preparative ultracentrifugation.) Standard lipids where determined by classical biochemical methods and the concentration and the size of the three main HDL subclasses were determined by Nuclear Magnetic Resonance (NMR). <h3>Results</h3> The SLE group presented a tendency to lower amount of triglycerides (TG) and esterified cholesterol (EC) carried by the large and medium HDL subclasses and a clear decrease up to 25% of the amount of TG and EC for the small HDL subclass (p=0,03). The average size of each HDL subclass was slightly smaller in the SLE group. Both results were not different in presence of a clinical flare. <h3>Conclusions</h3> The risk of the SLE patients to suffer a cardiovascular event is possibly increased due to a diminution of the HDL concentration and size, even during a period without a clinical flare. The capability of the HDL fraction in the reverse cholesterol efflux may possibly be compromised due to the changes in size and, consequently, in the HDL structure of the three subclasses. <h3>Disclosure of Interest</h3> None declared
Re: Giuseppe Magistro, Florian M.E. Wagenlehner, Magnus Grabe, Wolfgang Weidner, Christian G. Stief, J. Curtis Nickel. Contemporary Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome. Eur Urol 2016;69:286–97
Authors: Dino Papeš, Ana Jerončić
Journal: European Urology (2016)
Significance of Biopersistence in Relation to Pathogenic Effects in Humans: Role of Biopersistence in the Pathogenicity of Man-made Fibers and Methods for Evaluating Biopersistence: A Summary of Two Round-table Discussions
Authors: Roger O. McClellan, Thomas W. Hesterberg
Journal: Environmental Health Perspectives (1994)

This paper summarizes two roundtable discussions held at the conclusion of the International Conference on Biopersistence of Respirable Synthetic Fibres and Minerals. The first round table addressed the role of biopersistence in the pathogenicity of fiber-induced disease. The panel included T. W. Hesterberg (Chairman), J.M.G. Davis, K. Donaldson, B. Fubini, N.F. Johnson, G. Oberdoerster, P. Sebastien, and D. Warheit. The second panel addressed the issue of methods for assessing biopersistence. It included R.O. McClellan (Chairman), J. Brain, A. Langer, A. Morgan, C. Morscheidt, H. Muhle, and R. Musselman. The two chairmen acknowledge the excellent contributions of all the members of the panels, whose comments formed the basis of this summary. Nonetheless, the authors assume full responsibility for the written text, recognizing that it was not reviewed by the discussants of the two panels.—Environ Health Perspect 102(Suppl 5):277–283 (1994)
Small Traditional Human Communities Sustain Genomic Diversity over Microgeographic Scales despite Linguistic Isolation
Authors: Murray P. Cox, Georgi Hudjashov, Andre Sim, Olga Savina, Tatiana M. Karafet, Herawati Sudoyo, J. Stephen Lansing
Journal: Molecular Biology and Evolution (2016)

At least since the Neolithic, humans have largely lived in networks of small, traditional communities. Often socially isolated, these groups evolved distinct languages and cultures over microgeographic scales of just tens of kilometers. Population genetic theory tells us that genetic drift should act quickly in such isolated groups, thus raising the question: do networks of small human communities maintain levels of genetic diversity over microgeographic scales? This question can no longer be asked in most parts of the world, which have been heavily impacted by historical events that make traditional society structures the exception. However, such studies remain possible in parts of Island Southeast Asia and Oceania, where traditional ways of life are still practiced. We captured genome-wide genetic data, together with linguistic records, for a case-study system-eight villages distributed across Sumba, a small, remote island in eastern Indonesia. More than 4,000 years after these communities were established during the Neolithic period, most speak different languages and can be distinguished genetically. Yet their nuclear diversity is not reduced, instead being comparable to other, even much larger, regional groups. Modeling reveals a separation of time scales: while languages and culture can evolve quickly, creating social barriers, sporadic migration averaged over many generations is sufficient to keep villages linked genetically. This loosely-connected network structure, once the global norm and still extant on Sumba today, provides a living proxy to explore fine-scale genome dynamics in the sort of small traditional communities within which the most recent episodes of human evolution occurred.
Long-term outcome in juvenile-onset mixed connective tissue disease: a nationwide Norwegian study
Authors: Siri Opsahl Hetlevik, Berit Flatø, Marite Rygg, Ellen Berit Nordal, Cathrine Brunborg, Helene Hetland, Vibke Lilleby
Journal: Annals of the Rheumatic Diseases (2016)

Objectives To describe the characteristics, outcome and predictive factors of juvenile mixed connective tissue disease (JMCTD) in a nationwide cohort of patients. Methods We examined 55 patients with JMCTD after a mean disease duration of 16.2 years (SD 10.0). Patients were registered according to Kasukawa's criteria. Remission criteria were defined according to those for juvenile idiopathic arthritis, plus absence of cytopenia, myositis, progressive sclerodactyly, lung and oesophageal manifestations. Organ damage was assessed with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index and the Juvenile Arthritis Damage Index (JADI). Medical records were reviewed for early predictors for outcome, which were assessed by multivariate logistic regression analyses. Results Three patients developed systemic lupus erythematosus (SLE). Fifty-two patients had continuous JMCTD; the most common manifestations were: Raynaud (100%), arthritis (94%), puffy hands (77%) and pulmonary manifestations (58%). SLE-like, systemic sclerosis (SSc)-like and polymyositis (PM)-like findings were found in 98%, 77% and 48%, respectively. Over time, SLE-like and PM-like manifestations decreased, and SSc-like findings increased. At follow-up, 35 patients (67%) had active disease and 17 (33%) were in remission. In 34 patients (65%), SLICC or JADI≥1 assessments indicated organ damage. Active disease was associated with higher anti-ribonucleoprotein antibody titres at follow-up and positive rheumatoid factor (RF) at diagnosis and follow-up. Conclusions Most patients with JMCTD had active disease and organ damage after a mean follow-up of 16.2 years. Active disease was associated with higher anti-ribonucleoprotein antibody levels and positive RF. The presence of RF at diagnosis predicted persistent disease activity.
Preventing Microalbuminuria in Type 2 Diabetes
Authors: Michael Mauer, Paola Fioretto
Journal: New England Journal of Medicine (2005)

In subjects with type 2 diabetes and hypertension but with normoalbuminuria, the use of trandolapril plus verapamil and trandolapril alone decreased the incidence of microalbuminuria to a similar extent.The effect of verapamil alone was similar to that of placebo.
Cancer Mortality in Blacks
Authors: L D Leffall
Journal: CA A Cancer Journal for Clinicians (1974)

According to figures computed from data in the Official Statistics of the United States and verified with rates cited in Report 33 of the National Cancer Institute, the cancer mortality rate per 100,000 population for blacks of both sexes increased 20 percent between 1950 and 1967.It remained unchanged in whites.Surprisingly,