Background: To evaluate if TNF inhibitor serum drug levels (DL) or anti-drug antibodies (ADAb) can predict successful dose reduction (in patients with high DL) or discontinuation (in patients with no/low DL or ADAb) in rheumatoid arthritis (RA) patients.
Research design and methods: RA patients that were using adalimumab (n = 42), etanercept (n = 76) or infliximab (n = 51) and were doing well, were tapered until discontinuation or flare (1–1.5 year follow up). Random timed DL for adalimumab and etanercept and trough DL for infliximab were measured before dose reduction: Receiver-Operator-Curves (ROC) analyses with optimal cut-off DL were determined.
Results: No predictive value of adalimumab and infliximab DL for all outcomes were found, except for an inverse association of lower etanercept DL and higher chance for successful dose reduction (Area Under the Curve (AUC) 0.36, 95% CI 0.23–0.49; cut-off <2.6 mg/l). In sub analyses, higher adalimumab trough DL predicted successful dose reduction (AUC 0.86, 0.58–1.00; cut-off >7.8). ADAb were infrequent and not predictive of successful discontinuation.
Conclusions: No predictive value of baseline adalimumab, etanercept and infliximab DL or ADAb for successful dose reduction or discontinuation in RA was found in this context, with the possible exception of high adalimumab trough levels for successful dose reduction. 相似文献
The Film Digital Radiography System (FilmDRS) is a device with a laser optical film digitizer, 2,000 X 2,000 X 12-bit memory, and a 1,000-line video display. To evaluate the adequacy of this device for general radiography of the chest, four readers independently analyzed both radiographs and the corresponding video display of the digitized chest images of 150 patients, consisting of 100 images of abnormalities and 50 normal images. The overall results indicate equal sensitivity for the two systems. The FilmDRS, with interactive windowing, proved superior in the detection of hilar and mediastinal disease. X-ray film was superior in allowing detection of hyperlucent states. There was equivalent sensitivity for other disease categories. Superior specificity was achieved with conventional radiographs. 相似文献
The systemic administration of IFN-alpha/beta was previously found to
suppress inflammation in rats with experimental autoimmune uveoretinitis
(EAU); however, an effect on the systemic immune response was not
identified. In order to investigate an immunological basis for suppression
at the intraocular level, rats immunized with interphotoreceptor
retinoid-binding protein (IRBP) were administered daily intramuscular
injections of 10(5) IU IFN-alpha/beta and cytokines were measured by ELISA
in intraocular extracts prepared by ultrasonification at various timepoints
throughout the course of EAU. In control EAU, intraocular concentrations of
IFN-gamma were found to be non-detectable on day 8 before the onset of
inflammation, significantly elevated on day 12 at peak inflammation
(182+/-106 pg/ml), then non-detectable again on day 16 after inflammation
had begun to subside. In contrast, intraocular IFN-gamma in IFN-alpha/beta-
treated rats remained non-detectable or low at all timepoints. Measurement
of intraocular IL-2 revealed no difference between the two groups of rats.
Intraocular IL-4 concentrations were elevated in rats treated with
IFN-alpha/beta, although this cytokine was also detected in the same range
in controls as well as normal rats. Finally, intraocular IL-10 was
non-detectable on day 8, significantly elevated at peak inflammation on day
12 (588+/-139 pg/ml), then decreased to low levels on day 16 in control EAU
rats, while remaining non-detectable or low in IFN-alpha/beta-treated rats.
These results suggest that acute inflammation in IRBP-induced EAU in rats
involves both IFN-gamma and IL- 10 at the local intraocular level, and that
systemic administration of IFN-alpha/beta inhibits EAU via a mechanism that
involves suppression of both cytokines.
相似文献
Chronic wounds, such as venous ulcers and pressure ulcers, frequently remain unresponsive to currently available treatments. Several animal models of wound healing have been published, including models of impaired healing developed to mimic the clinical condition of chronic wounds better. We used a delayed wound healing model in the pig that uses irradiation of the skin prior to creation of the surgical wounds and characterized it histologically. Radiation was used on one side of the back prior to making four full-thickness wounds on each side. Clinical observations were performed to record granulation tissue, reepithelialization, and wound area as a function of time. Histology data were obtained at 1, 2, 3, and 4 weeks, and slides were stained with hematoxylin and eosin for general observations. Immunohistochemistry was performed using laminin as a marker for blood vessels, and the number, size, and circularity of blood vessels found in the granulation tissue were measured. Our results show that this model causes a delay in wound healing that is mostly apparent between days 7 and 15. Granulation tissue took more time to form and fill the wounds on the irradiated side, and blood vessels were slower to develop. Blood vessels were larger and more irregular in shape on the irradiated side than on the control side. After 2 weeks, healing resumed, indicating that the induced damage was not irreversible. These results suggest that this model can be used to test the effects of therapeutic approaches intended to treat chronic wounds. 相似文献
OBJECTIVE--To evaluate whether an insulin regimen with a long-acting zinc insulin (Ultratard HM) could help control fasting hyperglycemia in insulin-dependent diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS--A randomized sequential crossover trial with 6-wk treatment periods was used. Ten IDDM patients from the diabetes clinic at the Medical School who had persistent fasting hyperglycemia (greater than 10 mmol/L) were studied. Patients with nocturnal hypoglycemia were excluded. All patients completed the study. Insulin regimens consisted of three daily injections of a short-acting insulin (Actrapid HM) before meals and either a long-acting zinc insulin (Ultratard HM) or an intermediate isophane insulin (Protaphane HM) before the evening meal. Each regimen was followed for 6 wk. RESULTS--Fasting blood glucose levels (at 06:00 and 08:00) were significantly lower after the long-acting insulin regimen (6.26 +/- 0.88 vs. 10.82 +/- 4.27 mM, P less than 0.05 and 9.26 +/- 1.02 vs. 14.03 +/- 1.08 mM, P less than 0.05, respectively). Plasma-free insulin levels mirrored blood glucose concentrations because they were significantly higher at 06:00 and 08:00 after the long-acting insulin regimen (49.5 +/- 10.1 vs. 20.1 +/- 4.3 pM, P less than 0.05 and 31.6 +/- 5.0 vs. 16.5 +/- 3.4 pM, P less than 0.05, respectively). At any other time of the day, blood glucose and plasma insulin levels were not significantly different with either one of the two insulin regimens. CONCLUSIONS--A long-acting zinc human insulin injected before the evening meal can help to control persistent fasting hyperglycemia in IDDM patients. 相似文献
Summary— In order to test whether the β-adrenoceptor activity in rheumatic heart valvular disease depends on the ventricular load conditions, we determined their density and binding affinity to [125I]-iodocyanopindolol in lymphocytes, as well as plasma catecholamine and cAMP levels in 69 patients with regurgitant and stenotic lesions of the aortic and mitral valves. The patients were classified as having left ventricular pressure overload (LVP), left ventricular volume overload (LVV), mixed lesions (MOL) or right ventricular pressure overload (RVP). The β-adrenoceptor activity was determined by radioligand binding methods, catecholamines by high performance liquid chromatography using an electrochemical detector and cAMP by radioimmunoassay. The mean β-adrenoceptor density (Bmax) of the control group was 60.1 ± 9.5 /mol ( n = 29) per 106 lymphocytes. In the study population, the density was decreased by 83% in LVP, 78% in LVV, 87% in MOL and 86% in RVP. Plasma norepinephrine was elevated by 89% in LVP and 60% in MOL, epinephrine by 43% in LVP, 50% in VOL, 115% in MOL and 20% in RVP, while dopamine was not significantly changed, and cAMP was slightly elevated in all four groups. Screening for activating mutational changes in the Gsα-protein gave negative results, possibly dissociating the elevation in plasma cAMP from stimulatory effects of such abnormalities in the Gs-protein signaling. These results show a significant attenuation in lymphocyte β-adrenoceptor density of patients with rheumatic heart valvular disease, irrespective of the type of the prevailing ventricular load conditions. The reduction in receptor density is accompanied by a significant increase in plasma norepinephrine levels in patients with a left ventricular pressure overload and epinephrine in those with volume overload. 相似文献
The relationship between impaired glucose tolerance (IGT) and blood lipid levels was examined in 65 IGT individuals and in two control groups: control group I, composed of age-, sex-, and body weight-matched controls, and control group II, including normal subjects matched for sex and age but with normal body mass index. IGT individuals were found to have significantly higher total triglyceride (Tg) values compared with normal weight controls (P less than 0.001), while no difference was found between IGT and control group I. Total cholesterol levels were similar in IGT and each of the control groups. No significant correlation was found between serum lipoproteins and blood glucose levels either fasting or after load. 相似文献