tbuckley/cabot-search huggingface dataset:
Influence of anti-tumour necrosis factor therapy on cardiovascular risk factors in patients with active rheumatoid arthritis
Authors: C Popa
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Tumour necrosis factor (TNF) is known to increase the concentrations of interleukin (IL) 6 and C reactive protein (CRP) and to induce proatherogenic changes in the lipid profile and may increase the cardiovascular risk of patients with rheumatoid arthritis (RA) and other inflammatory disorders. <b>Objective:</b> To assess whether anti-TNF therapy modifies the cardiovascular risk profile in patients with RA. <b>Methods:</b> The lipoprotein spectrum and the inflammation markers CRP and IL6 were investigated in 33 patients with RA treated with human anti-TNF monoclonal antibodies (D2E7, adalimumab, Humira) and 13 patients with RA given placebo, before and after 2 weeks' treatment. <b>Results:</b> In the anti-TNF treated group, the mean (SD) concentrations of HDL-cholesterol were significantly higher after 2 weeks' treatment (0.86 (0.30) mmol/l <i>v</i> 0.98 (0.33) mmol/l, p&lt;0.01), whereas LDL and triglyceride levels were not significantly changed. Additionally, a significant decrease in CRP (86.1 (54.4) mg/l <i>v</i> 35.4 (35.0) mg/l, p&lt;0.0001), and IL6 (88.3 (60.5) pg/ml <i>v</i> 42.3 (40.7) pg/ml, p&lt;0.001) concentrations was seen in this group. No changes in lipid profile, IL6, or CRP levels were seen in the placebo group. <b>Conclusions:</b> TNF neutralisation with monoclonal anti-TNF antibodies increased HDL-cholesterol levels and decreased CRP and IL6 levels after 2 weeks. Therefore this treatment may improve the cardiovascular risk profile of patients with RA.
Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety
Authors: John T. Walkup, Anne Marie Albano, John Piacentini, Boris Birmaher, Scott N. Compton, Joel T. Sherrill, Golda S. Ginsburg, Moira A. Rynn, James McCracken, Bruce Waslick, Satish Iyengar, John S. March, Philip C. Kendall
Journal: New England Journal of Medicine (2008)

Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy.
Neurosteroids: Expression of Steroidogenic Enzymes and Regulation of Steroid Biosynthesis in the Central Nervous System
Authors: Ayikoe G. Mensah-Nyagan, Jean-Luc Do-Rego, Delphine Beaujean, Van Luu-The, Georges Pelletier, Hubert Vaudry
Journal: Pharmacological Reviews (1999)

Steroid hormones, which are synthesized in the adrenal gland, gonads and placenta, exert a large array of biological effects on the nervous system. In particular, steroid hormones play an important role in the development, growth, maturation, and differentiation of the central nervous system (CNS)2
Weight changes and the risk of knee osteoarthritis requiring arthroplasty
Authors: P Manninen
Journal: Annals of the Rheumatic Diseases (2004)

To examine the effect of weight changes between 20 and 50 years of age on the risk of severe knee osteoarthritis (OA) requiring arthroplasty.Cases were 55-75 year old men and women (n = 220) having had knee arthroplasty for primary osteoarthritis at the Kuopio University Hospital in 1992-93. Controls (n = 415) were randomly selected from the population of Kuopio Province. Weight at the age of 20, 30, 40, and 50 years was collected retrospectively with a postal questionnaire.After adjustment for age, sex, history of physical workload, recreational physical activity, and previous knee injury, weight gain resulting to a shift from normal body mass index (BMI < or =25 kg/m(2)) to overweight (BMI >25 kg/m(2)) was associated with a higher relative risk of knee OA requiring arthroplasty than persistent overweight from 20-50 years of age, compared with those with normal relative weight during the corresponding age period. The odds ratios (OR) were 3.07 (95% confidence interval 1.87 to 5.05) for those with normal weight at the age of 20 years and overweight at two or three of the ages 30, 40 or 50 years, 3.15 (1.85 to 5.36) for those with overweight from the age of 30 years, and 2.37 (1.21 to 4.62) for those with overweight from the age of 20 years, respectively.In adult life, a shift from normal to overweight may carry a higher risk for knee OA requiring arthroplasty than does constant overweight.
Reverse Transcription of Spliced psbA mRNA in Chlamydomonas spp. and Its Possible Role in Evolutionary Intron Loss
Authors: Obed W. Odom, David L. Herrin
Journal: Molecular Biology and Evolution (2013)

Reverse transcription of mRNA is thought to be an important first step in a model that explains certain evolutionary changes within genes, such as the loss of introns or RNA editing sites. In this model, reverse transcription of mRNA produces cDNA molecules that replace part of the parental gene by homologous recombination. In vivo evidence of reverse transcription of physiologically relevant mRNAs is generally lacking, however, except in genetically engineered cells. Here, we provide in vivo evidence for reverse transcription of the chloroplast psbA mRNA in two naturally occurring species of Chlamydomonas (raudensis and subcaudata) that is based on the presence of spliced cDNAs in both organisms. The psbA cDNAs, which lack the group II intron of the genomic gene, are nearly full length, and the majority of them—though not all—are in the form of RNA–cDNA hybrids. Moreover, the presence in these species of psbA cDNAs is correlated with the loss of an early group I intron from the same psbA gene. The group II intron that interrupts psbA in C. raudensis and C. subcaudata potentially encodes a protein with a reverse transcriptase domain, and the C. raudensis protein was shown to have reverse transcriptase activity in vitro. These results provide strong evidence for reverse transcription of a physiologically important mRNA (psbA) in two species of Chlamydomonas that have also lost an intron from the same gene, possibly through recombination with the cDNA.
Cardiac tamponade in juvenile chronic arthritis: report of two cases and review of publications.
Authors: J Goldenberg, A.P Pessoa, S Roizenblatt, R.M Pávoa, M.O Hilário, E Atra, M.B Ferraz
Journal: Annals of the Rheumatic Diseases (1990)

Two cases of systemic juvenile chronic arthritis, complicated by cardiac tamponade and eight previously reported cases are described. The clinical features and radiological, electrocardiographic, and echocardiographic findings were similar for all cases. One patient in this series was treated with corticosteroids and underwent pericardiectomy, dying of sepsis 30 days after surgery. The other patient was also treated with corticosteroids, underwent pericardiocentesis and developed fatal ventricular tachycardia. Of the 10 cases, only six were successfully treated. Early diagnosis and appropriate treatment are essential for a favourable outcome.
CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells
Authors: S. A. Quezada
Journal: Journal of Clinical Investigation (2006)

CTL-associated antigen 4 (CTLA4) blockade releases inhibitory controls on T cell activation and proliferation, inducing antitumor immunity in both preclinical and early clinical trials. We examined the mechanisms of action of anti-CTLA4 and a GM-CSF–transduced tumor cell vaccine (Gvax) and their impact on the balance of effector T cells (Teffs) and Tregs in an in vivo model of B16/BL6 melanoma. Tumor challenge increased the frequency of Tregs in lymph nodes, and untreated tumors became infiltrated by CD4+Foxp3– and CD4+Foxp3+ T cells but few CD8+ T cells. Anti-CTLA4 did not deplete Tregs or permanently impair their function but acted in a cell-intrinsic manner on both Tregs and Teffs, allowing them to expand, most likely in response to self antigen. While Gvax primed the tumor-reactive Teff compartment, inducing activation, tumor infiltration, and a delay in tumor growth, the combination with CTLA4 blockade induced greater infiltration and a striking change in the intratumor balance of Tregs and Teffs that directly correlated with tumor rejection. The data suggest that Tregs control both CD4+ and CD8+ T cell activity within the tumor, highlight the importance of the intratumor ratio of effectors to regulators, and demonstrate inversion of the ratio and correlation with tumor rejection during Gvax/anti-CTLA4 immunotherapy.
Enumeration of lymphocyte populations defined by surface markers in the whole blood of patients with Crohn's disease.
Authors: E O Pepys, E A Fagan, G A Tennent, V S Chadwick, M B Pepys
Journal: Gut (1982)

The proportions and absolute numbers of different lymphocyte populations were determined using alkaline phosphatase-labelled reagents in the whole peripheral blood of 22 patients with Crohn9s disease. Monoclonal mouse anti-T cell antibody (OKT3) was used to identify T cells, polyvalent F(ab9)2 anti-human immunoglobulin for B cells, C3b for C3b-receptor bearing cells, and soluble IgG antibody-antigen complexes for Fc(gamma)-receptor bearing cells. Endogenous myeloperoxidase served to distinguish monocytes. Application of this methodology to whole blood avoids the inevitable loss of cells which accompanies separation of mononuclear cells from blood and therefore permits precise enumeration of lymphocyte populations in the circulation. No significant difference from healthy adult controls was observed in any of the lymphocyte subsets tested.
Comparative studies of mononuclear phagocyte function in patients with Crohn's disease and colon neoplasms.
Authors: W L Beeken, S St Andre-Ukena, R M Gundel
Journal: Gut (1983)

Phagocytosis and cellular cytotoxicity by mononuclear phagocytes of blood and intestinal mucosa were studied in patients with Crohn9s disease and large bowel neoplasms. Antibody coated sheep erythrocytes were used for phagocytic assays and cellular cytotoxicity in vitro was measured by 24 hour isotope release from 75Selenium methionine-labelled RPMI 4788 human cancer cell cultures in the presence of mononuclear phagocyte-enriched effector populations. The mean percent of mononuclear phagocytes in Ficoll-Hypaque purified mononuclear cell suspensions of blood of healthy controls was 25.9 compared with 44.6 in patients with Crohn9s disease, 45.6 in patients with colon neoplasms and 11.6 in intestinal mucosa. Phagocytic indices were similar in all groups, but the phagocytic capacity of mucosal macrophages was twice that of blood monocytes. Mean cytotoxicity of monocytes of patients with Crohn9s disease was 12.8% compared with 22.9% for monocytes from normal controls, and 29.4% for patients with colon tumours. Mean cytotoxicity by mucosal macrophages was 18.0% compared with 13.2% by mucosal lymphocyte populations. Exposure of monocytes of Crohn9s disease patients to bacterial lipopolysaccharide modestly increased cytotoxicity, but exposure did not alter phagocytosis by monocytes of patients or controls. The results indicate that monocytes of patients with Crohn9s disease exhibit subnormal in vitro cytotoxicity. Mucosal macrophages from patients with various diseases show enhanced phagocytosis compared with blood monocytes, and they can mediate cellular cytotoxicity in vitro.
"CF asthma": what is it and what do we do about it?
Authors: I M Balfour-Lynn
Journal: Thorax (2002)

The diagnosis of "CF asthma" is problematic and it is difficult to determine which patients have a combination of CF and asthma and which have asthma like symptoms caused by inflammation of the CF lung. This may not matter, however; the relevance lies in the possible approaches to treatment.
Genetically Engineered <i>Salmonella typhimurium</i> as an Imageable Therapeutic Probe for Cancer
Authors: Vu H. Nguyen, Hyung-Seok Kim, Jung-Min Ha, Yeongjin Hong, Hyon E. Choy, Jung-Joon Min
Journal: Cancer Research (2009)

Tumor-targeting bacteria have been studied in terms of their ability to visualize the infection pathway (through imaging probes) or to carry therapeutic molecules to tumors. To integrate these monitoring and therapeutic functions, we engineered attenuated Salmonella typhimurium defective in guanosine 5'-diphosphate-3'-diphosphate synthesis to carry cytotoxic proteins (cytolysin A) and express reporter genes. We successfully visualized the therapeutic process with these engineered bacteria in mice and found that they often mediated complete tumor (CT-26) eradication on cytotoxic gene induction. Furthermore, treatment with the engineered bacteria markedly suppressed metastatic tumor growth.
Bronchoalveolar lavage cell analysis in a child with chronic lipid pneumonia
Authors: F Midulla, PM Strappini, V Ascoli, MP Villa, L Indinnimeo, C Falasca, S Martella, R Ronchetti
Journal: European Respiratory Journal (1998)

In an asymptomatic 4 yr old child with radiographic evidence of parenchymal lung disease, bronchoalveolar lavage (BAL) yielded the diagnosis of chronic lipid pneumonia caused by chronic aspiration of mineral oil given as a laxative. BAL analysis showed a marked reduction in the total number of alveolar macrophages; almost 70% of these cells contained intracytoplasmic lipid vacuoles. It also disclosed lymphocytic (cytotoxic/suppressor) alveolitis. A high percentage of lymphocytes expressed antigen markers of activation (human leucocyte antigen (HLA)-DR), CD54 and CD25). BAL analysis 18 months after mineral oil intake revealed that lymphocytes bearing antigen markers of activation had markedly decreased whereas alveolar macrophages (normal and lipid-laden) had increased. A subsequent whole lung BAL was considered unnecessarily invasive in this otherwise healthy child.
Physician Participation in Capital Punishment
Authors: Oscar W. Clarke
Journal: JAMA (1993)

<h3>BACKGROUND</h3> The question of physician participation in capital punishment has a long history.<sup>1</sup>Physicians have helped develop execution methods that were more humane than conventional methods. The most famous example is that of Dr Joseph Guillotin, who developed a mechanism for execution that he believed to be far more humane and civilized than other contemporary methods.<sup>2</sup>However, other physicians have disagreed with any physician participation in the death penalty.<sup>1</sup>The Oath of Hippocrates has historically been interpreted as prohibiting physician participation in executions. The Oath states in part: I will use treatment to help the sick according to my ability and judgment, but never with a view to injury and wrong-doing. Neither will I administer a poison to anyone when asked to do so nor will I suggest such a course.<sup>1</sup> During the 1970s, states began to consider use of lethal injection when executing condemned prisoners.
Why don't doctors worry about being under-prepared?
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2014)

Many people are prepared to work as doctors. It's a job that exudes status, excitement and competence. Doctors themselves often think otherwise. Try explaining to a misty-eyed sixth form student that a medical career doesn't suit everybody – and even those it might suit experience difficult moments that question their conviction. Many other professions look to medicine as a shining example of equal opportunities. Women and ethnic minorities are well represented. Medicine from the outside seems fair and desirable.

Voices from the inside tell a different story. Previous research shows that some 50% of doctors do not believe that medical school is an adequate preparation for work. This isn't uniquely a UK phenomenon. In a survey of German doctors, 60% felt ill-prepared for work.1 Dig deeper in this month's analysis of UK data and you discover that a further 25–30% of doctors do not believe that a lack of preparedness is a problem.2

These data are surprising for at least two reasons. First, almost every doctor I've spoken to on the subject has never pretended that medical school is an adequate preparation to begin work as a doctor. Either younger doctors, those in this study qualified in 2008 and 2009, are a better prepared bunch, they felt unable to tell the truth, or I keep strange company. Second, how is it possible to be ill-prepared for work, a job that immediately involves life or death situations, and not consider your lack of preparation to be a problem?

The point of this particular study is to look for differences in preparedness between sexes and ethnic groups. In short, women feel less prepared for work than men, although not to the same extent that non-whites feel less prepared than white doctors. This latter finding seems unlikely to be related to language or ‘culture' shock but may be a consequence of differing expectations of work life. These differences merit further exploration, although the dominant factor in level of preparedness is medical school.

That does make sense. Medical schools vary in their preparation of doctors but all must be failing to some degree. The pressure point, as shown by this month's research paper, isn't necessarily clinical skills; it is in the ‘job' of doctoring – clinical procedures, administrative tasks, interpersonal skills and physical and emotional demands. These issues are familiar to deans of medical schools and educators but is the current undergraduate medical education system doing enough to tackle these failings? It would be complacent to say yes.
A Longitudinal Investigation of Mortality in Anorexia Nervosa and Bulimia Nervosa
Authors: Debra L. Franko, Aparna Keshaviah, Kamryn T. Eddy, Meera Krishna, Martha C. Davis, Pamela K. Keel, David B. Herzog
Journal: American Journal of Psychiatry (2013)

Objective Although anorexia nervosa has a high mortality rate, our understanding of the timing and predictors of mortality in eating disorders is limited. The authors investigated mortality in a long-term study of patients with eating disorders. Method Beginning in 1987, 246 treatment-seeking female patients with anorexia nervosa or bulimia nervosa were interviewed every 6 months for a median of 9.5 years to obtain weekly ratings of eating disorder symptoms, comorbidity, treatment participation, and psychosocial functioning. From January 2007 to December 2010 (median follow-up of 20 years), vital status was ascertained with a National Death Index search. Results Sixteen deaths (6.5%) were recorded (lifetime anorexia nervosa, N=14; bulimia nervosa with no history of anorexia nervosa, N=2). The standardized mortality ratio was 4.37 (95% CI=2.4–7.3) for lifetime anorexia nervosa and 2.33 (95% CI=0.3–8.4) for bulimia nervosa with no history of anorexia nervosa. Risk of premature death among patients with lifetime anorexia nervosa peaked within the first 10 years of follow-up, resulting in a standardized mortality ratio of 7.7 (95% CI=3.7–14.2). The standardized mortality ratio varied by duration of illness and was 3.2 (95% CI=0.9–8.3) for patients with lifetime anorexia nervosa for 0 to 15 years (4/119 died), and 6.6 (95% CI=3.2–12.1) for those with lifetime anorexia nervosa for >15 to 30 years (10/67 died). Multivariate predictors of mortality included alcohol abuse, low body mass index, and poor social adjustment. Conclusions These findings highlight the need for early identification and intervention and suggest that a long duration of illness, substance abuse, low weight, and poor psychosocial functioning raise the risk for mortality in anorexia nervosa.
IMMUNOPATHOGENESIS OF ACUTE CENTRAL NERVOUS SYSTEM DISEASE PRODUCED BY LYMPHOCYTIC CHORIOMENINGITIS VIRUS
Authors: Donald H. Gilden, Gerald A. Cole, Neal Nathanson
Journal: The Journal of Experimental Medicine (1972)

Lymphocytic choriomeningitis (LCM) virus carriers were established by intracerebral inoculation of adult BALB/c mice followed by a single dose of cyclophosphamide (CY) (150 mg/kg) 3 days after infection, and by intracerebral injection within 24 hr of birth. These carriers were then adoptively immunized with spleen cells or serum from immune or normal BALB/c donors. Transfer of immune spleen cells into drug-induced carriers consistently resulted in acutely fatal choriomeningitis, histologically strikingly similar to classical LCM. Normal spleen cells or immune serum failed to produce either central nervous system (CNS) pathology or illness with any regularity. In addition, focal necrosis of the cerebellum was seen after adoptive immunization of drug-induced carriers but only when mice received cells at least 3 wk after inoculation, which is probably explained by the gradual spread of infection from membranes to the neural parenchyma during the first month after establishment of the carrier state in adult mice. Immune spleen cells, when transferred to neonatal carriers, led to a decrease in virus titers in blood and brains and to development of antibody without acute CNS disease. It appears that the production of fatal choriomeningitis after LCM infection is determined in part by the distribution of viral antigen, and this is markedly different in neonatal and drug-induced carriers at the time of cell transfer. Another factor of potential importance is the much higher level of circulating viral antigen in the plasma of neonatal than in that of drug-induced LCM carriers. Classical LCM disease can only be transferred by immune lymphoid cells and not by antiserum. Furthermore, little or no complement-fixing (CF) antibody was found in the plasma of mice dying of acute choroiditis. These observations strongly suggest that acute choroiditis is dependent upon the cell-mediated immune response.
Physician Attitudes About Sickle Cell Disease and Sickle Cell Trait
Authors: Dale B. Kellon
Journal: JAMA (1974)

An increased awareness of sickle cell disease in the black community has developed in recent years. Consequently, many screening programs to detect this disease and the trait have been instituted. Numerous anecdotal reports dealing with apparent malignant medical consequences of sickle cell trait have appeared. Nevertheless, except for hematuria, well-documented adverse clinical effects have been observed only under unusual stressful circumstances and cannot be considered an important threat to most sickle cell trait carriers.<sup>1</sup>The information to be gained by the detection of carriers in screening programs is, therefore, usually not clinically relevant to the carrier who is identified. Its main value would have to be in genetic counseling. Clearly, the impact of any screening program must depend ultimately on the information available to the medical profession. This is true especially for those individuals directly involved in screening programs and providing medical and genetic information to people with positive