tbuckley/cabot-search huggingface dataset:
Exclusion of close linkage of the dopamine transporter gene with schizophrenia spectrum disorders
Authors: A M Persico, Z W Wang, D W Black, N C Andreasen, G R Uhl, R R Crowe
Journal: American Journal of Psychiatry (1995)

Involvement of genetic factors in the pathogenesis of schizophrenia spectrum disorders has been indicated in twin, adoption, and familial aggregation studies; the pivotal role played by the dopamine transporter in dopaminergic neurotransmission makes it a candidate gene for these disorders. Detection of close linkage between a dopamine transporter marker and schizophrenia spectrum disorders would strongly support the existence of causal relationships between genetic mutations at the dopamine transporter locus and the disease phenotype.The authors assessed the linkage between this gene and schizophrenia spectrum disorders by using polymorphic dopamine transporter gene markers in 156 subjects from 16 multiplex pedigrees with schizophrenia as well as schizophreniform, schizoaffective, and schizotypal disorders and mood-incongruent psychotic depression.Complete (theta = 0.0) linkage to the schizophrenia spectrum was excluded under both dominant and recessive models.These results indicate that allelic variants at the dopamine transporter locus do not provide major genetic contributions to the etiology of schizophrenia and related disorders in these pedigrees.
Dried blood spots can help decrease the burden on patients dually infected with multidrug-resistant tuberculosis and HIV
Authors: Marlanka A. Zuur, Onno W. Akkerman, Daan J. Touw, Tjip S. van der Werf, Frank Cobelens, David M. Burger, Martin P. Grobusch, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2016)

HIV and tuberculosis (TB) are among the leading causes of death due to an infectious disease worldwide [1]. HIV co-infection was present in 12% of all TB cases in 2014; the African region accounted for 74% of those [1]. It has become crystal clear that both infections must be addressed simultaneously. Additionally, multidrug resistance (MDR) and extensive drug resistance (XDR) aggravate the problem even more [2]. The risk of having a poor MDR-TB treatment outcome is up to 10-fold higher among HIV co-infected individuals [3]. The pill burden for patients with MDR-TB with HIV co-infection is high and consists of a combination of at least six to 10 different drugs [2]. Therefore, drug–drug interactions, adverse drug reactions and/or suboptimal plasma concentrations are common [3]. Ultimately, the goal is to tailor both TB and HIV treatment (precision treatment) to optimise outcome and reduce adverse drug events in a way that is cost-effective and feasible worldwide. Of note, in nonaffluent settings where there is high disease co-endemicity, this requires a minimalist yet effective approach while resources are limited. What are needed are tools to determine the concentrations of all drugs, and treatment response markers by means of HIV viral load, and sputum smear and culture. TDM with dried blood spots can simply and simultaneously monitor treatment in patients with MDR-TB with HIV <http://ow.ly/TKIo300mwIY>
Symptoms and the genetics of schizophrenia: implications for diagnosis
Authors: R H Dworkin, M F Lenzenweger
Journal: American Journal of Psychiatry (1984)

To determine whether genetic influences in schizophrenia are related to the symptoms specified by diagnostic criteria, the case histories of 151 pairs of monozygotic twins from five twin studies of schizophrenia were rated for positive and negative symptoms. Concordance rates in monozygotic twins were significantly higher when probands had a greater number of negative symptoms; no evidence of a similar relationship was found for positive symptoms. The data indicate that negative symptoms may be characteristic of schizophrenia in which there is a greater genetic component. The results have important implications for determining diagnostic criteria and understanding the pathogenesis of schizophrenia.
AB0749 Is There Any Causal Relationship Between Infliximab Immunogenicity and Auto-Antibody Formation in Ankylosing Spondylitis Patients with Secondary Infliximab Treatment Failure
Authors: O. Rumyantseva, A. Botchkova, S. Krasnenko, M. Cherkasova, E. Alexandrova, S. Erdes
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> It has been mentioned, that continuous infliximab (Inf) therapy may be associated with increasing titers of antibodies (AB) to dsDNA and ANF, or emergence of neutralizing ABs, leading to loss in drug efficacy. <h3>Objectives</h3> To study the correlation between anti-Inf ABs and increased levels of ANF and anti-dsDNA ABs in serum of patients with ankylosis spondylitis (AS) and loss of Inf efficacy. <h3>Methods</h3> The study included 26 AS (mNY criteria) patients (15 males and 11 females) with secondary Inf treatment failure after continuous (&gt;1 year) effective therapy. Secondary failure was determined as loss of Inf efficacy within 4 weeks after two consecutive infusions. In all patients routinely were measured anti-dsDNA ABs (ELISA), ANF (indirect immunofluorescence) and anti-Inf ABs were quantified (ELISA with commercial Immunodiagnostik AG, Germany, kit). <h3>Results</h3> In 18 (69%) patients anti-Inf ABs were detected, in 19 (73%) – maximal ANF titers of 1/1280, in 17 (54%) – anti-dsDNA ABs (maximal value – 260 IU/ml). In 9 (35%) patients anti-Inf ABs coexisted with ANF and anti-dsDNA ABs, in 4 (15%) patients – only with ANF, and in another one – only anti-dsDNA ABs. Only in 1 patient with anti-Inf ABs no autoantibodies were detected. In 5 out of 8 patients without anti-Inf ABs, nevertheless, ANF and anti-dsDNA auto-antibodies were present, and in remaining 3 – either ANF or anti-dsDNA ABs were found. No was no significant correlation between formation of auto-antibodies and anti-Inf ABs (Spearman rank test). <h3>Conclusions</h3> Infliximab-neutralizing antibodies in AS patients with lost drug efficacy usually appear in parallel with autoantibodies, although no relationship between formation of these types of ABs has been established. <h3>Disclosure of Interest</h3> None declared
Spontaneous Spinal Epidural Hematoma
Authors: P L Penar, D K Fischer, I Goodrich, G M Bloomgarden, F Robinson
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
SAT0035 Chondroprotective Effects of IL-6 Inhibition Through Blockade of the STAT3 Pathway
Authors: A. Latourte, C. Cherifi, H.-K. Ea, W. Bouaziz, T. Funck-Brentano, M. Cohen Solal, E. Hay, P. Richette
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> High levels of interleukin-6 (IL-6) have been found in the synovial fluid of patients with osteoarthritis (OA), suggesting that IL-6 may be involved in the pathogenesis of OA. <h3>Objectives</h3> To investigate the effects of IL-6 in chondrocytes and to determine its main signalling pathways. To study the impact of IL-6 inhibition in an experimental mice model of OA. <h3>Methods</h3> The effects of IL-6 (10-50-100 ng/mL) were determined in vitro (primary culture of mouse chondrocytes) and ex vivo (mouse femoral head articular cartilage). Proteoglycan content (Alcian blue and Safranin O staining, DMM blue assay), expression of catabolic factors (qPCR, Western Blot, immunostaining), NO and PGE2 production and apoptosis (TUNEL assay) were evaluated. IL-6-induced signalling pathways were determined by Western Blot. The impact of STAT3 blockade was investigated using a specific inhibitor – Stattic – ex vivo and in a mice model of OA induced by destabilization of the medial meniscus (DMM). <h3>Results</h3> In vitro and ex vivo, IL-6 dose-dependently induced a dramatic loss of proteoglycan content through an increase in the expression of MMP3, MMP13, ADAMTS4 and ADAMTS5. By contrast, IL-6 had no effect on col2, aggrecan, col10 or VEGF. IL-6 induced chondrocytes apoptosis without increasing NO or PGE2 production. Inhibition of STAT3 by Stattic counteracted the catabolic and pro-apoptotic effects of IL-6 ex vivo. Finally, we orally administrated either Stattic (25 mg/kg/2d) or a saline for 6 weeks in C57/Bl6 mice (n=18) subjected to DMM. The severity of the OA lesions as assessed with the OARSI histological score was significantly lower in the Stattic group: 2.65±1.44 vs. 4.5±0.93 (p=0,004). <h3>Conclusions</h3> Our findings indicate that IL-6 has numerous catabolic effects in cartilage, mainly mediated by STAT3. STAT3 blockade protects against DMM-induced OA in mice, suggesting that IL-6 might be a promising therapeutic target in OA. <h3>Disclosure of Interest</h3> None declared
PWE-122 Autoimmune hepatitis (aih): assessment of usefulness of diagnosic liver biopsy and of “simplified” diagnostic scoring system
Authors: VM Gordon, A Dube, E Mcfarlane, M Karajeh, D Gleeson
Journal: Gut (2015)

<h3>Introduction</h3> Although recommended in published guidelines, only 62% of UK Gastroenterologists routinely recommend diagnostic liver biopsy in patients with suspected AIH (Dhaliwal Gut 2012:62). Also, the relative usefulness of the International AIH Group diagnostic criteria (full 1999 or simplified 2008) is not established. Our aim was to assess the relationships between histological and immunological diagnostic features and response to treatment in patients meeting the 1999 IAIHG criteria, which we also assessed against the 2008 simplified criteria. <h3>Method</h3> 90 patients were identified; 79% women, with median age 61 yrs (14–85) presenting since 2006 with suspected AIH and underwent diagnostic liver biopsy. Histology was assessed using the Ishak system by one liver Histopathologist (AKD) without reference to other results. <h3>Results</h3> Interface hepatitis was found in 87(97%) of biopsies, mainly plasma cell infiltrate in 74(83%), rosettes in 68(76%) and emperipolesis in 100% (of 48 patients assessed). Biliary changes were seen in 14% and mild steatosis in 24%. Prior to biopsy, patients had 13(7–19) diagnostic points by IAIHG criteria, with 11 of the 90 patients not having the required 10 points. Biopsy contributed an additional 5(0–6) points and all patients then met the 1999 IAIHG criteria (61 definite, 29 probable) with 17(12–22) points. In 49 patients, with a pre biopsy score of &gt;13, biopsy contributed 4(0–5) points and was not needed for diagnosis of AIH but detected biliary changes in 10 patients (3 AMA -ve,1 weak +ve subsequently diagnosed as PBC and started on treatment, 2 PSC overlap and 4 not overlap) and also detected cirrhosis in 9. Histological features did not differ between: patients with (n = 68) and without (n = 22) serum autoantibodies (nuclear, smooth muscle or LKM-1); between those with (n = 72) and without (n = 10) raised serum IgG; or between treated patients who did (n = 75) and did not (n = 8) achieve normal serum ALT within 6 months. Eighteen patients (20%) did not meet the 2008 simplified diagnostic criteria for AIH (6 points). In these, necro-inflammatory score was 9(2–15), fibrosis score was 3(0–5) and 13 of 14 treated patients achieved normal serum ALT by 6 months. <h3>Conclusion</h3> Liver biopsy is important for diagnosis of AIH in those with lower, but less so in those with higher pre-biopsy IAIHG (1999) diagnostic scores. It may also detect cirrhosis or indicate additional unsuspected biliary disease. Histological features are not associated with immunological features or response to treatment. The 2008 simplified diagnostic criteria will “miss” 20% of patients with AIH by 1999 criteria. Most of these patients have significant disease and respond to treatment. <h3>Disclosure of interest</h3> None Declared.
MEDICAL EDUCATION IN ENGLAND.
Authors: P G Lankisch
Journal: JAMA (1890)

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
Blockade of Interplay between IL-17A and Endoplasmic Reticulum Stress Attenuates LPS-Induced Lung Injury
Authors: So Ri Kim, Hee Jung Kim, Dong Im Kim, Kyung Bae Lee, Hae Jin Park, Jae Seok Jeong, Seong Ho Cho, Yong Chul Lee
Journal: Theranostics (2015)

IL-17 is a cytokine mainly from IL-17-producing T cells, which are one of subsets of CD4+ T cells and play a role in adaptive immune system. Recent studies have demonstrated that IL-17A can act rapidly as an innate immune responder during infection before the onset of its classic adaptive immune response. This role of IL-17A in innate immune response is implicated in lipopolysaccharide (LPS)-induced lung inflammation. Very recently, we have reported that endoplasmic reticulum (ER) stress is involved in LPS-induced lung inflammation in vivo and in vitro. This study aimed to elucidate the role of IL-17A in LPS-induced lung injury, focusing on the link with ER stress. We treated a murine model of LPS-induced lung injury with IL-17A neutralizing antibody and 4-phenylbutyrate (4-PBA), a representative ER stress inhibitor. In addition, we evaluated the effects of IL-17A on ER stress in LPS-stimulated bronchial epithelial cells. Our results showed that inhibition of IL-17A decreased LPS-induced pulmonary neutrophilia, vascular leakage, nuclear translocation of nuclear factor-κB (NF-κB), infiltration of dendritic cells, increased expression of Toll-like receptor 4 (TLR4), activation of NLRP3 inflammasome, and increased ER stress in the lung. 4-PBA or TAK-242, a TLR4 inhibitor attenuated expression of IL-17A thereby improving LPS-induced lung inflammation. Intriguingly, we observed that stimulation with LPS increased expression of IL-17A in airway epithelial cells and co-stimulation with IL-17A further increased ER stress and NF-κB activation. This study indicates that the interrelationship between IL-17A and ER stress plays an important role in LPS-induced injury showing a positive feedback in airway epithelial cells and suggests that targeting their interaction can be a potential therapeutic approach to overcome one of severe refractory pulmonary disorders.
ATPS-74IS MORE CHEMOTHERAPY BETTER? PROLONGED SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA RECEIVING MORE THAN SIX CYCLES OF ADJUVANT TEMOZOLOMIDE
Authors: Jacob Ruzevick, Emily Silgard, Carrie Graham, Maciej Mrugala
Journal: Neuro-Oncology (2015)

OBJECTIVE: To determine if prolonging therapy beyond the standard six cycles of post-radiation temozolomide is associated with improved survival in patients with newly diagnosed glioblastoma (GBM). INTRODUCTION: GBM is the most common malignant primary brain tumor in adults and is associated with a poor prognosis. Standard of care calls for surgery, radiation, and 6 cycles of chemotherapy with the alkylating agent, temozolomide. Several small studies have shown a potential survival benefit to prolonged courses of adjuvant temozolomide. Moreover, in clinical practice, duration of therapy varies across the USA. METHODS: A retrospective review of patients diagnosed with GBM was performed. Baseline patient information including sex and KPS was obtained. Patients were stratified into one of three groups as determined by the number of post-radiation temozolomide cycles completed: Group I: Fewer than six cycles; Group II: six cycles and; Group III: Seven or more cycles. Baseline KPS was compared using ANOVA. Survival was plotted using Kaplan-Meier analysis. Median survival was compared using a log rank test. RESULTS: A total of 97 patients with pathology-confirmed GBM and known chemotherapy regiments were included. All patients underwent surgical resection and radiation therapy. Sixty-two(64%) patients were treated with fewer than 6 cycles of temozolomide (Range 1-5), 12(12%) patients were treated with 6 cycles of temozolomide, and 23(24%) patients were treated with 7 or more cycles of temozolomide (Range: 7-24). There was no statistical difference in the mean baseline KPS between groups (p = 0.18). The median survival was 511 days for patients treated with fewer than 6 cycles, 717 days for patients treated with 6 cycles, and 1193 days for patients treated with more than 6 cycles of temozolomide (p = 0.007). CONCLUSIONS: In patients with newly diagnosed GBM, prolonged adjuvant temozolomide chemotherapy beyond the standard 6 cycles is associated with improved survival. Prospective study is needed to validate these results.
Precipitating Clinical Factors, Heart Failure Characterization, and Outcomes in Patients Hospitalized With Heart Failure With Reduced, Borderline, and Preserved Ejection Fraction
Authors: John R Kapoor, Roger Kapoor, Christine Ju, Paul A Heidenreich, Zubin J Eapen, Adrian F Hernandez, Javed Butler, Clyde W Yancy, Gregg C Fonarow
Journal: JACC Heart Failure (2016)
Relationship of Adenosine 3′,5′-Cyclic Monophosphate and Guanosine 3′,5′-Cyclic Monophosphate to Growth of Dimethylbenz[ a ]anthracene-Induced Mammary Tumors in Rats 2 3 4
Authors: Robert J. Matusik, Russell Hilf
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Relationship of Adenosine 3′,5′-Cyclic Monophosphate and Guanosine 3′,5′-Cyclic Monophosphate to Growth of Dimethylbenz[a]anthracene-Induced Mammary Tumors in Rats Get access Robert J. Matusik, Robert J. Matusik 5Department of Biochemistry and the University of Rochester Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, N.Y. 14642. Search for other works by this author on: Oxford Academic PubMed Google Scholar Russell Hilf Russell Hilf 6 5Department of Biochemistry and the University of Rochester Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, N.Y. 14642. 7We thank Paul Whitman for his technical assistance. 6Address reprint requests to Dr. Russell Hilf. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 3, March 1976, Pages 659–661, https://doi.org/10.1093/jnci/56.3.659 Published: 01 March 1976 Article history Received: 29 July 1975 Accepted: 29 September 1975 Published: 01 March 1976
Soundings: Unsung heroes
Authors: Kevin Barraclough
Journal: BMJ (2004)

I often feel besieged by all the guidance documents from various committees. The difficulty is both the volume and the fact that they rarely tell you not to do something. I should apparently be urgently referring everyone with a sore throat of more than six weeks' duration and anyone with any dysphagia (even a teenager with tonsillitis?).

A recent editorial in this journal referred to general practice as the “risk sink” of a publicly funded health service (BMJ 2003;326: 234-5 [PubMed]). Every day hundreds of thousands of investigations are not done because generalists, or specialists, accept that the risk-benefit balance doesn't warrant it. These people are the unsung heroes that maintain the viability of the NHS.

In the 1980s the guidance was for general practitioners never to initiate angiotensin converting enzyme (ACE) inhibitors in patients with heart failure. It had to be done in hospital. Even a few years ago the guidance defining those patients who must be admitted into hospital to have ACE inhibitors initiated included most patients I would ever see with heart failure. It was necessary to ignore the unrealistic guidance, with the associated medico-legal risk, or else burden unnecessarily an already collapsing hospital system.

It is quite rare to come across guidance that states explicitly that there must be some threshold of risk at which the investigation should not be done. But there must be such a threshold and, as it is a threshold, there will necessarily be some diagnoses that will be missed. The corollary of this, I suppose, is that if a clinician never misses a diagnosis then they are either not seeing enough patients (an old adage), or they are over-investigating those they do see.

The real problem is that the downsides of over-investigation—the patient anxiety generated and the resources clogged up—are hidden. It is the one missed case of colorectal cancer, even though its finding may have been incidental to the presenting symptom, that leads to charges of incompetence. But whoever hears criticism of the doctor who refers everything?

We need realistic guidelines. We try to capture as many early diagnoses as possible. But it is necessary to recognise that, unless we medicalise the whole of society, there will be occasions when, as the Americans say, shit happens. And it is not necessarily our fault.