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21.
Azathioprine therapy in chronic ulcerative colitis 总被引:7,自引:0,他引:7
A H Steinhart J P Baker A Brzezinski E J Prokipchuk 《Journal of clinical gastroenterology》1990,12(3):271-275
We evaluated the efficacy of azathioprine (Az) therapy in chronic ulcerative colitis (CUC) retrospectively in a clinic population from 1977 to 1987. The study was an open one. Sixteen patients were treated with a total of 20 courses of Az. Mean dose of Az was 1.48 mg/kg/d (range 0.98-1.82). All patients were on oral prednisone at the initiation of Az therapy. Indications for Az were: inability to wean off steroids without symptoms of CUC (12/20), poor response to steroids (7/20), and steroid toxicity (1/20). Responses to Az occurred in 15/20 courses (12/16 patients). Two patients had side effects requiring Az discontinuation. The mean duration of follow-up was 52.6 months with no incidence of malignancies. We conclude that the use of Az in selected patients with CUC who are steroid resistant or steroid dependent may be both efficacious and safe. 相似文献
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Samantha R. Slight Leticia Monin Radha Gopal Lyndsay Avery Marci Davis Hillary Cleveland Tim D. Oury Javier Rangel-Moreno Shabaana A. Khader 《The American journal of pathology》2013,183(5):1397-1404
IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10–deficient mice (Il10−/−), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10−/−-infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain.Francisella tularensis, a facultative intracellular bacterium, because of its infectious nature and the severe disease caused by low doses of airborne bacteria, has been classified as a category A select bioterrorism agent.1 Infection in humans is caused by two main subspecies, F. tularensis (type A) and Francisella holarctica (type B).2 An F. tularensis live vaccine strain (LVS) has been developed from the F. tularensis B strain as an experimental vaccine, but is not licensed for use in humans.1
F. tularensis LVS has been used as a representative attenuated model to address the immune requirements for protection against Francisella. By using this model, the importance of IL-12 in driving interferon γ (IFN-γ) and T-helper cell 1 (Th1) responses in immunity to F. tularensis LVS infection is well described.3–5 In contrast, IL-17 is generally thought to play a role in protection against extracellular, but not intracellular, pathogens.6 However, we and others recently identified a protective role for IL-17 in the induction of cellular immunity to F. tularensis LVS pulmonary infection,7–9 by driving the production of IFN-γ through IL-12 induction.7 IL-17 is a proinflammatory cytokine also known to induce chemokines, such as keratinocyte chemoattractant, macrophage inflammatory protein 2 (MIP-2), and granulocyte colony-stimulating factor (G-CSF), to mediate granulopoiesis, neutrophil recruitment, and inflammation.6 Accordingly, the absence of IL-17 during F. tularensis LVS pulmonary infection also results in decreased induction of G-CSF and MIP-2, as well as decreased accumulation of neutrophils and lung inflammation.7 Neutrophil depletion alone does not affect bacterial control after pulmonary infection with F. tularensis LVS,10 suggesting that the role for IL-17 in driving Th1 responses, and not neutrophil recruitment, was the primary immune mechanism mediating protection in this model.7 These data together suggest that both IL-17 and IFN-γ are required for generating protective immunity to pulmonary F. tularensis LVS infection.IL-10 is an anti-inflammatory cytokine best studied for its inhibitory effects on IL-12 production and down-regulation of Th1 responses.11 Accordingly, IL-10–deficient mice show enhanced protection in models of intracellular bacterial infections, such as Mycobacterium tuberculosis12 and Listeria monocytogenes.13 In addition, in a cutaneous model of F. tularensis LVS infection, IL-10–deficient mice exhibit increased protection, and this was reversed when IL-17 was depleted.14 In contrast to these published studies, in the current study, we report that after pulmonary infection with F. tularensis LVS, mice deficient in IL-10 (Il10−/−) exhibit increased mortality. We clearly demonstrate that the increased mortality in the Il10−/−-infected mice is not associated with loss of protective immunity, because bacterial burden between wild-type and Il10−/− mice is similar, but is caused by exacerbated inflammation and increased lung pathology. We demonstrate that the exacerbated inflammation observed in Il10−/−-infected mice is the result of unrestrained IL-17 production and IL-17–dependent recruitment of neutrophils and resulting lung pathology. These data together suggest that, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis LVS,7,9 IL-17 production is tightly regulated by anti-inflammatory cytokines, such as IL-10. Our studies highlight how inflammatory cytokines, such as IL-17, can be beneficial for host protection, but when produced unrestrained, can mediate host pathology. 相似文献
24.
Mari E. Tanaka Holly R. Brideau Thomas J. An Theresa C. McLoud Brent P. Little Hillary R. Kelly 《Current problems in diagnostic radiology》2021,50(3):351-355
PurposeThis study aimed to assess the efficacy of a virtual information session hosted by a diagnostic radiology residency program at addressing applicant concerns about the 2020-2021 interview cycle and highlighting key aspects of the residency program.MethodsParticipants were recruited to attend the virtual information session over a 2-week period via social media and communication with medical school radiology interest groups. Attendees were able to submit questions or topics of interest prior to the session. The virtual information session was hosted by trainees and faculty from a radiology residency. Data regarding the demographics of the attendees and the efficacy of the session were obtained through interactive live polling during the virtual session and a voluntary anonymous postsession survey.ResultsA total of 171 attendees participated in the virtual information session. Of the attendees, 42% learned about the session from Twitter and 72% were fourth-year medical students applying for residency. Among topics addressed during the session, attendees indicated that they were most interested in learning about “Application strategies during COVID-19” during an in-session poll. On the post-session survey, 96% of attendees reported being more knowledgeable about the residency program culture and the breadth of research and educational opportunities.ConclusionGiven the virtual nature of the 2020-2021 residency application cycle, utilization of web-based platforms for recruitment will be essential. Virtual information sessions can be effective at providing insight into aspects of a residency program that are typically gained during the in-person interview experience. 相似文献
25.
A DNA Segment Spanning the Mouse Tnfsf11 Transcription Unit and Its Upstream Regulatory Domain Rescues the Pleiotropic Biologic Phenotype of the RANKL Null Mouse
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26.
Berg KM Kunins HV Jackson JL Nahvi S Chaudhry A Harris KA Malik R Arnsten JH 《The American journal of medicine》2008,121(5):406-418
Objective
Alcoholism is a risk factor for osteoporotic fractures and low bone density, but the effects of moderate alcohol consumption on bone are unknown. We performed a systematic review and meta-analysis to assess the associations between alcohol consumption and osteoporotic fractures, bone density and bone density loss over time, bone response to estrogen replacement, and bone remodeling.Methods
MEDLINE, Current Contents, PsychINFO, and Cochrane Libraries were searched for studies published before May 14, 2007. We assessed quality using the internal validity criteria of the US Preventive Services Task Force.Results
We pooled effect sizes for 2 specific outcomes (hip fracture and bone density) and synthesized data qualitatively for 4 outcomes (non-hip fracture, bone density loss over time, bone response to estrogen replacement, and bone remodeling). Compared with abstainers, persons consuming from more than 0.5 to 1.0 drinks per day had lower hip fracture risk (relative risk = 0.80 [95% confidence interval, 0.71-0.91]), and persons consuming more than 2 drinks per day had higher risk (relative risk = 1.39 [95% confidence interval, 1.08-1.79]). A linear relationship existed between femoral neck bone density and alcohol consumption. Because studies often combined moderate and heavier drinkers in a single category, we could not assess relative associations between alcohol consumption and bone density in moderate compared with heavy drinkers.Conclusion
Compared with abstainers and heavier drinkers, persons who consume 0.5 to 1.0 drink per day have a lower risk of hip fracture. Although available evidence suggests a favorable effect of alcohol consumption on bone density, a precise range of beneficial alcohol consumption cannot be determined. 相似文献27.
Nancy Cardinez Leif E. Lovblom Johnny-Wei Bai Evan Lewis Alon Abraham Daniel Scarr Julie A. Lovshin Yuliya Lytvyn Genevieve Boulet Mohammed A. Farooqi Andrej Orszag Alanna Weisman Hillary A. Keenan Michael H. Brent Narinder Paul Vera Bril David Z. Cherney Bruce A. Perkins 《Journal of diabetes and its complications》2018,32(7):660-664
Aim
Neuropathy and neuropathic pain are common complications of type 1 diabetes (T1D). We aimed to determine if sex-specific differences in neuropathic pain are present in adults with longstanding T1D.Methods
Canadians with ≥50?years of T1D (n?=?361) completed health history questionnaires that included assessment of neuropathy (defined by Michigan Neuropathy Screening Instrument questionnaire components ≥3; NEUROPATHYMNSI-Q) and neuropathic pain. Multivariable logistic regression was used to determine sex-differences in neuropathic pain controlling for neuropathy.Results
Participants had mean age 66?±?9?years, median diabetes duration 53[51,58] years, mean HbA1c 7.5?±?1.0%, and 207(57%) were female. Neuropathic pain was present in 128(36%) of all participants, more prevalent among those with NEUROPATHYMNSI-Q compared to those without [96(63%) vs. 31(15%), p?<?0.001], and more prevalent in females compared to males [87(42%) vs. 41(27%), p?=?0.003]. Independent of the presence of NEUROPATHYMNSI-Q and other factors, female sex was associated with the presence of neuropathic pain [OR 2.68 (95% CI 1.4–5.0), p?=?0.002].Conclusions
We demonstrated a novel sex-specific difference in neuropathic pain in females compared to males with longstanding T1D, independent of the presence of neuropathy. Further research using more objective measures of neuropathy than the MNSI is justified to further understand this sex-specific difference. 相似文献28.
It is widely accepted that a relationship exists between inner ear morphology and functional aspects of an animal's biology, such as locomotor behaviour. Animals that engage in agile and spatially complex behaviours possess semicircular canals that morphologically maximise sensitivity to correspondingly complex physical stimuli. Stemming from the prediction that fossorial tetrapods require a well‐developed sense of spatial awareness, we investigate the hypothesis that fossoriality leads to inner ear morphology that is convergent with other spatially adept tetrapods. We apply morphometrics to otic capsule endocasts of 26 caecilian species to quantify aspects of inner ear shape, and compare these with a sample of frog and salamander species. Our results reveal caecilians (and also frogs) possess strongly curved canals, a feature in common with spatially adept species. However, significantly shorter canals in caecilians suggest reduced sensitivity, possibly associated with reduced reliance on vestibulo‐ocular reflexes in this group of visually degenerate tetrapods. An elaboration of the sacculus of caecilians is interpreted as a unique adaptation among amphibians to increase sensitivity to substrate‐borne vibrations transmitted through the head. This study represents the first quantitative analyses of inner ear morphology of limbless fossorial tetrapods, and identifies features within a new behavioural context that will contribute to our understanding of the biological consequences of physical stimuli on sensory function and associated morphological evolution. 相似文献
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Hillary L. Broder PhD MEd Maureen Wilson‐Genderson PhD Lacey Sischo PhD 《Journal of public health dentistry》2012,72(4):302-312
Objectives: This study assessed the reliability and validity of the Child Oral Health Impact Profile–Short Form 19 (COHIP‐SF 19) from the validated 34‐item COHIP. Methods: Participants included 205 pediatric, 107 orthodontic, and 863 patients with craniofacial anomalies (CFAs). Item level evaluations included examining content overlap, distributional properties, and use of the response set. Confirmatory factor analysis identified potential items for deletion. Scale reliability was assessed with Cronbach's alpha. Discriminant validity of the COHIP‐SF 19 was evaluated as follows: among pediatric participants, scores were compared with varying amounts of decayed and filled surfaces (DFS) and presence of caries on permanent teeth; for orthodontic patients, scores were correlated with anterior tooth spacing/crowding; and for those with CFA, scores were compared with clinicians' ratings of extent of defect (EOD) for nose and lip and/or speech hypernasality. Convergent validity was assessed by examining the partial Spearman correlation between the COHIP scores and a standard Global Health self‐rating. Comparisons between the COHIP and the COHIP‐SF 19 were completed across samples. Results: The reduced questionnaire consists of 19 items: Oral Health (five items), Functional Well‐Being (four items), and a combined subscale named Socio‐Emotional Well‐Being (10 items). Internal reliability is ≥0.82 for the three samples. Results demonstrate that the COHIP‐SF 19 discriminates within and across treatment groups by EOD and within a community‐based pediatric sample. The measure is associated with the Global Health rating (P < 0.05), thereby indicating convergent validity. Conclusions: Reliability and validity testing demonstrate that the COHIP‐SF 19 is a psychometrically sound instrument to measure oral health‐related quality of life across school‐aged pediatric populations. 相似文献