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Zampieri and colleagues used sophisticated statistical methods to create a picture of acid-base pattern and inflammation relationship in a clinical context. The observed independent relationship between acidosis and albumin concentration and inflammatory pattern opens up a new area for research. It has become clear that, in addition to the characterization of mediators, receptors, and cellular phenotypes, the inflammatory response has to be interpreted in light of acid-base status, albumin concentration, and probably also carbon dioxide level.Until now, the interplay between acid-base status and inflammation has received little attention, especially in a clinical context. The article by Zampieri and colleagues [1] in a previous issue of Critical Care is a pioneering study analyzing the relationship between acidosis variables, inflammatory mediators, and end-organ failures (acute kidney injury and shock). Since the metabolic and inflammatory reactions are simultaneous, the demonstration of interplay that is more than a simultaneous modification remains a difficult challenge. Because of this, the authors used three different statistical methods to separate the confounding factors. First, they developed a generalized linear model using the measured mediator as a dependent variable and components of acid-base status as variables. Second, they performed a multivariate adaptive regression with splines in order to evaluate the association of selected cytokines and acid-base components. Third, they performed a principal component analysis using Simplified Acute Physiology Score 3 as a way of quantifying illness severity in order to assess the independent association of acid-base variables and cytokine levels. The authors found that, in 87 prospective unselected patients, the level of strong anion gap (SIG) was positively associated with TNFα and IL-6, IL-8, and IL-10. A negative association was found between albumin level and TNFα and IL-6, IL-7, IL-8, and IL-10 and IFNγ. The conclusion drawn from these results opens up a new route for research to understand the mechanisms that link acid-base variables, albumin level, and immunological activation.Such a topic is important and clinically relevant since plasma and interstitial fluid constitute the microenvironment for immune and tissue cells. Acid-base and albumin characteristics may then interfere with the cell response to different signals such as endotoxin. In addition, both fluid resuscitation and capillary leak may largely influence the composition of the cell microenvironment, especially when a crystalloid such as saline or a balanced crystalloid such as Ringer’s lactate is used. The role of surrounding cell pH could be seen as a result of metabolic acidosis and carbon dioxide (CO2) level, an aspect that was not investigated in the study [2,3]. Given the picture presented in this article, some approaches might be tested to clarify the mechanisms involved in immune modifications induced by acid-base changes. First, immune cells should be drawn from septic patients that have been incubated in the septic plasma or drawn after replacement of septic plasma by healthy plasma; both acid-base conditions or albumin concentration can then be modified to test their impact on immune cells phenotype. This might help to clarify how the pH, the SIG, and albumin concentration change the immune cell phenotypes. Second, similar experiments with healthy cells incubated in plasma from acutely injured patients could be performed to demonstrate the role of physicochemical plasma patterns. Mediators and cell functions then could be evaluated in different acid-base conditions. Until now, few data on alkalosis have been reported in terms of immunity, and the essential information comes from acidosis situations. One author of the study was part of a group [4] that showed that metabolic acidosis induced by hydrochloric acid and lactic acidosis added to culture media of RAW 264.7 cells have opposite effects: hydrochloric acid at a pH of 7 seems essentially pro-inflammatory (nitric oxide level, IL-6/IL-10 ratio, NF-κB DNA binding), whereas lactic acidosis is essentially anti-inflammatory. A group with the same author, using a rat model, confirmed these results in terms of systemic cytokines [5]. In that study, the authors found a positive relationship between SIG and IL-6, IL-8, and IL-10 and TNFα, which was independent of illness severity. Even though albumin was not administered in the presented cohort, it can be discussed in light of immune effects. The authors observed a negative correlation between albumin level and IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 and IFNγ. In addition to its complex effects, albumin was shown to be immunosuppressive for peripheral blood monocytes (IFNγ and TNFα) and also for T lymphocyte clone [6], which confirmed the presented results. Except for specific indications, albumin is not recommended for use in fluid resuscitation, especially after the recent negative results of a randomized clinical trial [7]. Third, the role of hypo- or hypercarbia has to be investigated since elevated CO2 was shown to modulate mammalian inflammatory and innate immune responses in vitro and in vivo [3], independently of extra- and intra-cellular pH. During a sterile insult of inflammation stimulation, hypercapnia may be of benefit but would be deleterious in the setting of infection due to host immunosuppression. The underlying mechanism implicates the NF-κB signaling pathway as an important hub of CO2 sensitivity [3,8]. This, in combination with the ability of elevated CO2 to enhance bacterial and fungal virulence and survival, suggests that hypercapnia may predispose humans to infections or worsen outcomes [3]. Understanding the involved molecular signaling pathways will be of great importance in the identification of new approaches to control infection and inflammation in the clinical setting. 相似文献
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Olfa Saidane Ines Mahmoud Leila Gafsi Ajleni Houda Rawdha Tekaya Leila Abdelmoula 《The Egyptian Rheumatologist》2018,40(3):183-185
Background
The work productivity loss due to ankylosing spondylitis (AS) has a notable socioeconomic impact.Aim of the work
To evaluate the professional characteristics of Tunisian AS patients and determine conditions that lead to absenteeism.Patients and methods
99 AS patients were included. Disease characteristics and specific AS indices were assessed; Bath AS disease activity index (BASDAI), Bath AS disease functional index (BASFI), Bath AS disease global index (BASG-s), Bath AS radiologic index (BASRI), hospital anxiety and depression (HAD) scale and Shorts Form-36 (SF-36). Visual analogue scale was used to evaluate pain and fatigue. Patients were questioned on their work situation, work sector, work conditions (rhythm, posture, working hours, distance to workplace, duration of rest) and whether they have missed work time during the last three months because of their disease.Results
Mean age of patients was 40.02 ± 11.78 years; 70 men and 29 women. The mean disease duration was 11.87 ± 10.7 years. Absenteeism was present in 23.2% of the cases. Only the deterioration of the mental component of the SF-36 was associated with absenteeism (p = 0.03). Depression and anxiety states seemed not to increase absenteeism, gender and work sector had no influence. Factors significantly associated with absenteeism were increased working hours (p = 0.037), bad posture (p = 0.001), stress at work (p = 0.035) and insufficient day rest duration (p = 0.007). Carrying heavy loads tended to be more frequent in the absenteeism group (p = 0.08).Conclusion
Absenteeism is high amongst Tunisian AS patients. Work conditions were important factors of absenteeism in Tunisian AS patients that directly influence productivity. 相似文献45.
Helen L. Barrett Kathryn L. Gatford Candice M. Houda Miles J. De Blasio H. David McIntyre Leonie K. Callaway Marloes Dekker Nitert Suzette Coat Julie A. Owens William M. Hague Janet A. Rowan 《Diabetes care》2013,36(3):529-536
OBJECTIVE
This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated with metformin or insulin and in cord plasma of their offspring and to examine how these markers relate to infant size at birth.RESEARCH DESIGN AND METHODS
Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial. Fasting maternal plasma glucose, lipids, and CRP were measured at randomization, 36 weeks’ gestation, and 6–8 weeks postpartum as well as in cord plasma. Women with available cord blood samples (metformin n = 236, insulin n = 242) were included.RESULTS
Maternal plasma triglycerides increased more from randomization to 36 weeks’ gestation in women treated with metformin (21.93%) versus insulin (9.69%, P < 0.001). Maternal and cord plasma lipids, CRP, and neonatal anthropometry did not differ between treatments. In logistic regression analyses adjusted for confounders, the strongest associations with birth weight >90th centile were maternal triglycerides and measures of glucose control at 36 weeks.CONCLUSIONS
There were few differences in circulating maternal and neonatal markers of metabolic status and no differences in measures of anthropometry between the offspring of women treated with metformin and the offspring of women treated with insulin. There may be subtle effects of metformin on maternal lipid function, but the findings suggest that treating gestational diabetes mellitus with metformin does not adversely affect lipids or CRP in cord plasma or neonatal anthropometric measures.Gestational diabetes mellitus is carbohydrate intolerance first diagnosed during pregnancy (1) and affects up to 18% of pregnancies. The prevalence varies depending on maternal demographics and diagnostic criteria (2). The prevalence of gestational diabetes mellitus is increasing, which is likely driven by the rising population prevalence of overweight and obesity and increasing maternal age at pregnancy (3). Gestational diabetes mellitus increases maternal and infant morbidity and mortality during pregnancy (4). Women with a history of gestational diabetes mellitus are at risk for metabolic syndrome, type 2 diabetes (5), and cardiovascular disease in later life (6). Children born to women with gestational diabetes mellitus have higher rates of type 2 diabetes and obesity (7).Treating gestational diabetes mellitus improves pregnancy outcomes for both mother and infant (8). Current therapies include modification of diet, increased physical activity, and drug therapy with insulin and oral hypoglycemic agents, including metformin. In addition to improving insulin sensitivity and hyperglycemia, metformin therapy in the setting of type 2 diabetes reduces triglycerides (9), total cholesterol, LDL cholesterol (10), and VLDL cholesterol; increases HDL cholesterol (9); and reduces markers of inflammation and thrombosis (11). Metformin therapy in gestational diabetes mellitus achieves maternal glucose control and pregnancy outcomes similar to insulin therapy (12,13).In contrast to insulin, metformin crosses the placenta (14) and, therefore, could directly influence fetal metabolism. Our recent follow-up studies in 2-year-old offspring of women enrolled in the Metformin in Gestational Diabetes (MiG) trial showed increased subcutaneous fat measurements with no increase in abdominal adiposity or total fat (15). Further assessments are required to determine whether metformin actually reduces visceral/ectopic fat. Therefore, we hypothesized that metformin would be more effective than insulin in improving markers of insulin sensitivity and cardiovascular risk during pregnancy and postpartum in women with gestational diabetes mellitus and in their newborns. 相似文献46.
Smoking versus infection as the aetiology of bronchial mucous gland hypertrophy in chronic bronchitis 总被引:1,自引:1,他引:0
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Gamal E. Megahed Gamal A. Senna Mohammed H. Eissa Safeia Z. Saleh Houda A. Eissa 《Thorax》1967,22(3):271-278
The smoking habits of 50 proved cases of chronic bronchitis were studied. Bronchoscopy was done and a bronchial biopsy was taken for histological examination. Bronchial lavage was obtained under sterile conditions for bacteriological studies. The degree of bronchial mucous gland hypertrophy was determined, and the presence or absence of infection, as shown by the presence of potential pathogens in the bronchial lavage, was noted. We think that tobacco smoking and its resulting irritation to the bronchi is the most important underlying cause of bronchial mucous gland hypertrophy because there is: (1) a significantly higher incidence of mucous gland hypertrophy in smokers than in non-smokers among the 50 chronic bronchitics studied; (2) a significantly higher accumulated lifetime tobacco consumption in patients exhibiting mucous gland hypertrophy than in those without hypertrophy of the bronchial mucous glands; (3) a significant association and correlation between the degree of mucous gland hypertrophy and the intensity of smoking; and (4) no difference in the comparative frequency of occurrence of bronchial mucous gland hypertrophy in subjects with and without demonstrable infection, as shown by the presence of potential pathogens in the bronchial lavage. We could not deny that infection might be having an initiating or potentiating effect. 相似文献
47.
Megdiche Bazarbacha H Bouchriha M Sebai R Belghith L Touibi S 《La Tunisie médicale》2006,84(8):509-512
Hemangiocytoma are rare malignant vascular tumor. Vertebral location is uncommun. They occur preferentially at the lumbo-sacrul spine with paravertebral extension. The features include spinal pains, para vertebral tumefaction and paresthesia. The CT and MRI scans can help to diagnosis which is histological. The treatment is surgical combined or no with radiotherapy. The pronostic is marqued by the recidive risk and metastases. We report a new case of vertebral hemangiopericytoma of the thoraco-lumbar spine with litteratur review. 相似文献
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As a follow-up to the new classification of CYP3A inhibitors, the present work was undertaken to search for quantitative correlations of AUC ratios between sensitive substrates and midazolam (reference). A large set of clinical studies was obtained utilizing the M&T Drug Interaction Database, and recent Product Labels. Linear relationships were found between midazolam and four CYP3A substrates: simvastatin, buspirone, triazolam and eplerenone. Simvastatin and buspirone were consistently more sensitive than midazolam, independent of the inhibitor. Quantitative correlations of AUC ratios between four CYP3A inhibitors (fluconazole, erythromycin, verapamil, diltiazem) and ketoconazole (400 mg/day) were also uncovered. The average potencies of these inhibitors relative to ketoconazole were 27% for erythromycin, 17% for fluconazole and 19% for verapamil. 相似文献
50.