qMRI relaxometry of mandibular bone marrow: A monomodal distribution in sickle cell disease

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.     

Allosteric peptide regulators of chemokine receptors CXCR4 and CXCR7

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.     

Clinical review: What are the best hemodynamic targets for noncardiac surgical patients?

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.     

常规超声与超声造影在胰岛素瘤术前定位诊断中的对比研究

目的 比较分析常规超声与超声造影对胰岛素瘤术前定位诊断的价值.方法 回顾性分析经手术证实的47例胰岛素瘤患者的常规超声及超声造影图像,比较两种影像学方法对胰岛素瘤定位诊断的准确性.结果 与手术病理结果比较,常规超声诊断胰岛素瘤的敏感性和准确性均为27.7%;超声造影诊断胰岛素瘤的敏感性和准确性分别为91.5%、84.3%;两种影像学技术对胰岛素瘤的定位诊断准确率存在统计学差异(P<0.05,P＝0.0000).结论 在胰岛素瘤的术前定位诊断中,超声造影较常规超声定位更准确,在术前定位中具有重要的应用价值.     

Faecal mucus degrading glycosidases in ulcerative colitis and Crohn's disease.

Because the normal faecal flora includes bacteria which can produce mucus-digesting glycosidases, it follows that increased digestion of colonic mucus by these bacterial enzymes could be important in the pathogenesis of ulcerative colitis. Faecal activities of potential mucus-degrading glycosidases have therefore been assayed in samples from patients with inflammatory bowel disease and normal controls. The enzymes alpha-D-galactosidase, beta-D-galactosidase, beta-NAc-D-glucosaminidase alpha-L-fucosidase and neuraminidase were assayed. Considerable glycosidase activity was present in most faecal samples. Similar activities of all the enzymes assayed were found in faeces from patients with ulcerative colitis, Crohn's disease and normal controls and there was no significant correlation with disease activity. These results imply that relapse of ulcerative colitis is not initiated by increased degradation of colonic mucus by faecal glycosidases but do not exclude a role for bacterial mucus degradation in the pathogenesis of ulcerative colitis.     

Bronchoalveolar lavage: role in the pathogenesis, diagnosis, and management of interstitial lung disease

Bronchoalveolar lavage has emerged as a useful technique for the study of pulmonary interstitial disorders. Several types of information are provided by the evaluation of lavage fluid. First, the identification of cellular constituents helps to separate inflammatory processes in which lymphocytes predominate (for example, sarcoidosis, hypersensitivity pneumonitis, and berylliosis) from those in which neutrophils or macrophages predominate (for example, idiopathic pulmonary fibrosis and histiocytosis X). Second, the cells removed during lavage can be studied for their immune properties and function; tested with specific antigens, in diseases such as berylliosis and hypersensitivity pneumonitis; and examined for the presence of unique surface antigens with monoclonal antibodies (for example, histiocytosis X). Third, in conjunction with scanning electron microscopy and electron probe analysis, lavage makes possible the identification of inorganic particles in alveolar macrophages of patients with pneumoconiotic lung disease. Finally, although lavage is still an investigative procedure for most pulmonary disorders, it has an established role in the diagnosis of opportunistic infections in the immunocompromised patient.     

The efficacy of laparoscopy in acute cholecystitis.

OBJECTIVE: To evaluate the role of laparoscopic cholecystectomy in acute cholecystitis and establish the outcomes of this treatment modality at North Oakland Medical Centers. METHODS: This was a retrospective analysis over a three-year period (January 1, 1994 to December 31, 1996), performed at a University-affiliated urban teaching hospital, North Oakland Medical Centers, Pontiac, Michigan. Five hundred and fifty-seven patients underwent surgical treatment for gallbladder disease; 88 patients had acute cholecystitis, and 469 patients had chronic cholecystitis. Acute cholecystitis patients underwent surgery within 72 hours of the onset of symptoms; the patient's selection for laparoscopic cholecystectomy or open cholecystectomy depended on severity of disease, co-morbid factors and surgeon's preference. The parameters of age, gender, operating (OR) time, length of stay, complications, conversion rates from laparoscopic cholecystectomy to open cholecystectomy, and cost were compared in patients who underwent laparoscopic cholecystectomy and/or open cholecystectomy. RESULTS: Patients chosen to undergo laparoscopic cholecystectomy for acute cholecystitis tended to be younger females. Patients treated with laparoscopic cholecystectomy for acute cholecystitis had shorter OR times and LOS compared to patients treated with open cholecystectomy for acute cholecystitis. Conversion rates (CR) were 22% in acute cholecystitis and 5.5% in chronic cholecystitis during the study period; CR diminished considerably between the first and third year. Complications were also lower in patients who underwent laparoscopic cholecystectomy vs. open cholecystectomy. CONCLUSIONS: Laparoscopic cholecystectomy appears to be a reliable, safe, and cost-effective treatment modality for acute cholecystitis; however, the surgical approach should be cautionary because of the spectrum of potential technical hazards. CR is improving as surgeons gain experience.     

Renal findings on radiological followup of patients with Beckwith-Wiedemann syndrome

PURPOSE: The Beckwith-Wiedemann syndrome is most commonly characterized by macroglossia and abdominal wall defect(s), and it carries a predisposition to embryonal tumors, including Wilms tumor. We report our experience with the character and incidence of renal disease in patients with the Beckwith-Wiedemann syndrome, and discuss the role of radiological followup. MATERIALS AND METHODS: We reviewed the medical records of all patients diagnosed with the Beckwith-Wiedemann syndrome who were treated at our institution between March 1979 and February 1998. Radiological followup consisted of renal ultrasound at approximately 3 to 6-month intervals with the addition of computerized tomography or magnetic resonance imaging (MRI) in patients with an indeterminate lesion(s) or nephrogenic rest(s). RESULTS: A total of 29 patients were identified. Of these cases renal ultrasound showed normal kidneys bilaterally in 19 (70%), simple cysts in 5 (19%), indeterminate lesion(s) in 2 (7%) and nephrocalcinosis in 1 (4%). Nephrogenic rests were followed with MRI in 1 patient, and 1 in whom a 2 cm. mass was revealed by followup MRI underwent partial nephrectomy and chemotherapy for stage I Wilms tumor. CONCLUSIONS: The 3.7% incidence of Wilms tumor in our patients with the Beckwith-Wiedemann syndrome is similar to that in previously published reports. Aggressive follow-up by a sensitive radiological technique is warranted in cases of the Beckwith-Wiedemann syndrome, and associated hemihypertrophy and/or nephromegaly with or without evidence of a Wilms tumor precursor. The detection of suspected malignant disease at an early stage may permit curative nephron sparing surgery.