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81.
82.
Joseph H. Liao MD Hernan Jara PhD Rohini Nadgir MD Elliott Elias MD Nekou Nowrouzi Naoko Saito MD Martin H. Steinberg MD Osamu Sakai MD PhD 《Journal of magnetic resonance imaging : JMRI》2013,37(5):1182-1188
Purpose:
To identify and characterize sickle cell disease (SCD)‐related changes in the composition of mandibular bone marrow using qMRI relaxometry histograms.Materials and Methods:
Thirteen SCD patients and 17 controls underwent brain MR imaging with the mixed turbo spin‐echo (TSE) pulse sequence at 1.5T. The mandible was manually segmented and divided into body, angle, ramus, and condyle. T1 and T2 histograms of each mandible were modeled with Gaussian functions. The relaxation time histogram peaks were calculated, and the number of monomodal versus bimodal curves was compared.Results:
SCD patients exhibited monomodal distributions on both T1 and T2 histograms, consistent with a composition of predominantly red hematopoietic marrow. Eighty‐eight percent of mandibles in control subjects exhibited a bimodal distribution in T1 and all showed a bimodal distribution in T2, indicating mixed but predominantly yellow marrow composition. The second peak in control subjects was shorter in T1 and longer in T2, consistent with yellow marrow composition.Conclusion:
Instead of physiological fatty replacement, SCD patients exhibit red marrow persistence in the mandible, likely due to the increased demand for hematopoiesis. This phenomenon can be manifested by a monomodal curve in both T1 and T2 relaxometric histograms. J. Magn. Reson. Imaging 2013;37:1182–1188. © 2012 Wiley Periodicals, Inc. 相似文献83.
Anna Ehrlich Paramita Ray Kathryn E. Luker Elias J. Lolis Gary D. Luker 《Biochemical pharmacology》2013
The chemokine CXCL12 and its shared seven-transmembrane receptors CXCR4 and CXCR7 regulate diseases including cancer, atherosclerosis, autoimmunity, and HIV infection, making these molecules promising drug targets. These molecules also control key processes in normal development and physiology, suggesting the need to selectively modulate CXCR4 and/or CXCR7 functions and signaling to reduce potential complications of long-term therapy. We previously identified two peptides that functioned as allosteric agonists driving CXCR4-dependent chemotaxis, providing key structural information to design a small number of additional peptides to investigate determinants of CXCL12 interactions and signaling through CXCR4 and CXCR7. In the current study, we show that the previously identified peptides only minimally activated CXCR4 signaling through the cytosolic adapter protein β-arrestin 2 and do not initiate signaling to ERK1/2. By comparison, peptides with diverse N-terminal amino acid sequences effectively activated CXCR7 signaling to β-arrestin 2. One peptide, designated as GSLW based on its N-terminal amino acids, activated CXCR7 signaling and potentiated CXCL12-CXCR7 signaling without blocking the scavenger function of CXCR7 to internalize CXCL12. These results advance our understanding of CXCR7 ligand recognition and signaling, and provide structural information to target allosteric binding sites on this receptor as chemical probes and potential therapeutic agents. 相似文献
84.
Perioperative hemodynamic optimization, or goal-directed therapy (GDT), has been show to significantly decrease complications and risk of death in high-risk patients undergoing noncardiac surgery. An important aim of GDT is to prevent an imbalance between oxygen delivery and oxygen consumption in order to avoid the development of multiple organ dysfunction. The utilization of cardiac output monitoring in the perioperative period has been shown to improve outcomes if integrated into a GDT strategy. GDT guided by dynamic predictors of fluid responsiveness or functional hemodynamics with minimally invasive cardiac output monitoring is suitable for the majority of patients undergoing major surgery with expected significant volume shifts due to bleeding or other significant intravascular volume losses. For patients at higher risk of complications and death, such as those with advanced age and limited cardiorespiratory reserve, the addition of dobutamine or dopexamine to the treatment algorithm, to maximize oxygen delivery, is associated with better outcomes. 相似文献
85.
Niyaz Hareni Fredrik Strmqvist Bjrn Strmqvist Freyr Gauti Sigmundsson Bjrn E Rosengren Magnus K Karlsson 《Acta orthopaedica》2021,92(1):4
Background and purpose — Indication for lumbar disc herniation (LDH) surgery is usually to relieve sciatica. We evaluated whether back pain also decreases after LDH surgery.Patients and methods — In the Swedish register for spinal surgery (SweSpine) we identified 14,097 patients aged 20–64 years, with pre- and postoperative data, who in 2000–2016 had LDH surgery. We calculated 1-year improvement on numeric rating scale (rating 0–10) in back pain (Nback) and leg pain (Nleg) and by negative binomial regression relative risk (RR) for gaining improvement exceeding minimum clinically important difference (MCID).Results — Nleg was preoperatively (mean [SD]) 6.7 (2.5) and Nback was 4.7 (2.9) (p < 0.001). Surgery reduced Nleg by mean 4.5 (95% CI 4.5–4.6) and Nback by 2.2 (CI 2.1–2.2). Mean reduction in Nleg) was 67% and in Nback 47% (p < 0.001). Among patients with preoperative pain ≥ MCID (that is, patients with significant baseline pain and with a theoretical possibility to improve above MCID), the proportion who reached improvement ≥ MCID was 79% in Nleg and 60% in Nback. RR for gaining improvement ≥ MCID in smokers compared with non-smokers was for Nleg 0.9 (CI 0.8–0.9) and Nback 0.9 (CI 0.8–0.9), and in patients with preoperative duration of back pain 0–3 months compared with > 24 months for Nleg 1.3 (CI 1.2–1.5) and for Nback 1.4 (CI 1.2–1.5).Interpretation — LDH surgery improves leg pain more than back pain; nevertheless, 60% of the patients with significant back pain improved ≥ MCID. Smoking and long duration of pain is associated with inferior recovery in both Nleg and Nback.The most common indication for lumbar disc herniation (LDH) surgery is persistent sciatica that does not respond to nonoperative treatment (Blamoutier 2013). However, most patients who undergo LDH surgery also suffer from back pain (Hakkinen et al. 2003, Stromqvist et al. 2017), on a national level reported in 93% of patients having LDH surgery (Stromqvist et al. 2017). Decades ago, Mixter (1937) therefore argued that LDH extirpation should be accompanied by fusion to minimize postoperative back pain. Recent studies have opposed this view, showing that LDH surgery is not followed by increased back pain when only removing the hernia (Pearson et al. 2008, Owens et al. 2018), and in many cases even improvement of back pain seems sustainable over time.Most studies that evaluate the outcome of LDH surgery focus on the relief from sciatica and improvement in patient-reported outcome measures (PROMs) (Weber 1983, Atlas et al. 2005, Peul et al. 2007, Weinstein et al. 2008, Lurie et al. 2014). A few studies have focused on back pain or included back pain in the evaluation (Kotilainen et al. 1993, Hakkinen et al. 2003, Toyone et al. 2004, Atlas et al. 2005, Pearson et al. 2008, Owens et al. 2018). While some of these infer that back pain is improved by the LDH surgery (Hakkinen et al. 2003, Toyone et al. 2004, Pearson et al. 2008, Owens et al. 2018) others report inconclusive results (Kotilainen et al. 1993, Atlas et al. 2005). There is a lack of consensus on the expected level of back pain reduction with LDH surgery.It would also be of clinical interest to identify preoperative factors that are associated with favorable reduction of back pain following LDH surgery such as age, sex, smoking, preoperative health, and duration of pain (Nygaard et al. 2000, Jansson et al. 2005, Stromqvist et al. 2016, Wilson et al. 2016, Hareni et al. 2019).We (i) evaluated whether back pain is reduced after LDH surgery and if so, to what extent compared with the reduction in leg pain and (ii) what proportion of patients gain improvement in back and leg pain exceeding minimum clinically important difference (MCID). The secondary aim was to identify factors associated with improvement in back pain exceeding MCID. 相似文献
86.
87.
P R Evora J C Brasil M L Elias J R Arévalo R N Sgarbieri A C Menardi P J Ribeiro 《Cardiology》1988,75(4):287-288
The usual surgical treatment of tricuspid endocarditis is valve replacement or valve excision alone without valve replacement. 'Vegetectomy', i.e. local excision of the vegetation and leaflet repair, has been previously described and can be applied to cases with well-circumscribed vegetations and little or no valve damage. A case of tricuspid valve endocarditis successfully managed by surgical excision of the vegetation is reported. 相似文献
88.
NOD2 insertion mutation in a Cretan Crohn's disease population 总被引:5,自引:0,他引:5
Roussomoustakaki M Koutroubakis I Vardas EM Dimoulios P Kouroumalis EA Baritaki S Koutsoudakis G Krambovitis E 《Gastroenterology》2003,124(1):272-3; author reply 273-4
89.
Antidepressant induced cholestasis: hepatocellular redistribution of multidrug resistant protein (MRP2) 下载免费PDF全文
BACKGROUND: We report two cases of antidepressant induced cholestasis. Case reports: We describe the first reported case of acute cholestasis due to citalopram (selective serotonin reuptake inhibitor) occurring in a patient who also experienced obstetric cholestasis in association with each of three pregnancies; in a second patient cholestasis developed due to dothiepin (tricyclic antidepressant), and six years later due to paroxetine. In both cases liver biopsies showed features of a "pure" cholestasis with total resolution within 1-6 months after withdrawal of the causative drug. Immunostaining for the canalicular transporter, multidrug resistant protein 2 (MRP2), responsible for biliary secretion of several organic anions including bilirubin glucuronides, showed sustained expression in both biopsies as well as relocalisation with appearance of strong staining of the basolateral membrane of the hepatocyte. This finding has also not been reported previously. CONCLUSIONS: We postulate that intracellular redistribution of MRP2 may reflect an adaptive compensatory mechanism which helps in the elimination of the drug or its cholestatic metabolites from the hepatocyte back to the sinusoidal space and subsequent excretion in urine. Changes seen in these two patients differ from findings previously reported in rats where downregulation of mrp2 occurs in response to experimentally induced cholestasis. We speculate that the rat is more advanced than humans in its ability to downregulate canalicular transporter expression as protection against progressive intrahepatic cholestasis. 相似文献
90.
David Mutimer Nicolai Naoumov Pieter Honkoop George Marinos Monz Ahmed Robert de Man Penny McPhillips Mark Johnson Roger Williams Elwyn Elias Solko Schalm 《Journal of hepatology》1998,28(6):923-929
Background/Aims: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination.Methods: All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3′TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction.Results: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance).Conclusions: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotheraphy appears disappointing, and other treatment strategies should be investigated. 相似文献