Is the early cyclosporine A level predictive of the outcome of immunosuppressive therapy in severe aplastic anemia?

Immunosuppressive therapy (IST) has provided an alternative treatment option for cure of aplastic anemia patients who cannot receive bone marrow transplantation. Although there have been many recent studies on the efficacy of antithymoglobulin (ATG) combined with cyclosporine A (CsA), there is no data on the correlation between the variability of CsA levels and the response to IST. Therefore, we retrospectively assessed the factors associated with IST efficacy in patients with acquired severe aplastic anemia (SAA). Sixty‐six patients were treated with ATG combined with CsA for 6 months. In the response group, the CsA levels were increased rapidly to more than 200 ng/mL within the first 2 wk after starting the IST. However, the non‐response group had a pattern of slower increase of the CsA levels. The CsA levels, during the first and second week of treatment with IST, were significantly different in the responders and non‐responders. The factors predictive of response to IST and survival were analyzed. The univariate analysis showed that a younger age at the initiation of IST, a high absolute neutrophil count prior to starting IST, a short interval between the diagnosis and initiation of IST, and high CsA levels during the first and second week of IST treatment were positively associated with the response rate and overall survival. The multivariate analysis showed that these four factors were independent factors associated with a longer patient survival. A high response rate was associated with a short interval between diagnosis and initiation of IST as well as high CsA levels during the first and second week of IST. Therefore, early intensification of CsA levels might improve patient outcome.     

A dual echo approach to removing motion artefacts in fMRI time series

In fMRI, subject motion can severely affect data quality. This is a particular problem when movement is correlated with the experimental paradigm as this potentially causes artefactual activation. A method is presented that uses linear regression, to utilise the time course of an image acquired at very short echo time (TE) as a voxel‐wise regressor for a second image in the same echo train, that is acquired with high BOLD sensitivity. The value of this approach is demonstrated using task‐locked motion combined with visual stimulation. Results obtained at both 1.5 and 3 T show improvements in functional activation maps for individual subjects. The method is straightforward to implement, does not require extra scan time and can easily be embedded in a multi‐echo acquisition framework. Copyright © 2009 John Wiley & Sons, Ltd.     

Efficacy of rituximab in an aggressive form of multicentric Castleman disease associated with immune phenomena

Multicentric Castleman disease (MCD) is an uncommon lymphoproliferative disorder for which the best therapeutic option is not yet well established. Immune-related disorders are rare complications of MCD. We report on an MCD case in a 23-year-old patient with extensive abdominal involvement and associated immune hemolytic anemia and Raynaud phenomenon. He was negative for human immunodeficiency virus (HIV) and human herpesvirus-8 (HHV-8). After 8 courses of the anti-CD20 monoclonal antibody (rituximab), the patient achieved complete remission. Interestingly, Raynaud phenomenon disappeared under treatment and no new hemolytic events occurred. Anti-CD20 antibody treatment could be an attractive therapeutic approach for MCD, mainly when immune-related disorders are associated.     

Peripheral levels of matrix metalloproteinase-9, interleukin-6, and C-reactive protein are elevated in patients with acute coronary syndromes: correlations with serum troponin I

BACKGROUND: Acute coronary syndromes (ACS) are characterized by activation of systemic and local inflammatory mediators. The interrelation between these soluble inflammatory markers and their association with markers of myocardial necrosis have not been extensively studied. HYPOTHESIS: The study was undertaken to evaluate the association of the systemic levels of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), with C-reactive protein (CRP), interleukin-6 (IL-6), and serum troponin-I in patients admitted with ACS. METHODS: Analysis of serum concentrations of the above inflammatory markers was performed in 53 patients with unstable angina (UA) and in 15 with non-ST-segment elevation myocardial infarction (NSTEMI) within 48 h of admission, and 34 patients with stable coronary artery disease. RESULTS: Compared with patients with stable angina, those with ACS had elevated admission levels of MMP-9 (p = 0.04), CRP (p < 0.001), and IL-6 (p = 0.001), but not TIMP-1 (p = 0.55). Compared with patients with UA, those with NSTEMI also had higher levels of IL-6 (p < 0.001), CRP (p = 0.002), and MMP-9 (p = 0.05). CONCLUSIONS: In patients with ACS, the admission levels of inflammatory mediators, including MMP-9, CRP, and IL-6 are significantly elevated, specifically in association with serum troponin I. Systemic and local markers of inflammatory activity may be directly associated with myocardial injury.     

Left ventricular function in patients with coronary heart disease in the presence or absence of angina pectoris during exercise radionuclide ventriculography

This study compares left ventricular (LV) performance during exercise in patients with angiographically documented coronary artery disease (CAD) based on the presence or absence of angina pectoris during the index exercise tests. The patients were divided into 2 groups: Group I included 31 patients who had angina pectoris during the test and Group II included 43 who did not. Multivessel CAD was present in 21 patients (68%) in Group I and 26 patients (60%) in Group II (difference not significant [NS]). There were no significant differences between the 2 groups in age, sex, history of diabetes mellitus, history of myocardial infarction and in the exercise duration, work load, heart rate and systolic blood pressure. Exercise-induced ST-segment depression was present in 48% of the patients in Group I and in 40% in Group II (NS). The mean LV ejection fraction at rest was 52 ± 12% in Group I and 50 ± 17% in Group II (NS). There were significant differences in the 2 groups in the change from rest to exercise in ejection fraction (?4.5 ± 7.6% in Group I vs 1 ± 9.4% in Group II, p < 0.01), end-systolic volume (29 ± 38 ml in Group I vs 9 ± 23 ml in Group II, p < 0.005), the change in systolic blood pressure-to-end-systolic volume ratio (?0.1 ± 0.5 mm Hg/ml in Group I vs 0.3 ± 1.1 mm Hg/ml in Group II, p < 0.05), and wall motion score (?0.4 ± 0.6 in Group I vs 0.09 ± 0.7 in Group II, p < 0.05).Thus, asymptomatic myocardial ischemia may occur in patients with extensive CAD and be associated with abnormal exercise LV function; however, patients with symptomatic CAD have worse exercise LV function than those with asymptomatic CAD.     

875 Cases of bacterial meningitis: Diagnostic procedures and the impact of preadmission antibiotic therapy Part III of a three-part series

Data on the bacteriological findings, diagnostic measures and clinical course of 875 patients with bacterial meningitis are presented. Findings from the medical records and from a follow-up questionnaire survey of 667 of these cases revealed no significant difference between patients treated with antibiotics before admission (pretreated) and those who were not treated before admission (non-pretreated) with respect to clinical condition on admission, mortality and late sequelae. Pretreatment was, however, associated with a longer duration of symptoms. Apart from cases due to Neisseria meningitidis, there were no significant differences in diagnostic findings between pretreated and non-pretreated cases. In the group of pretreated meningococcal patients, however, positive blood cultures, pleiocytosis in the cerebrospinal fluid (CSF) and positive cultures from sites other than blood and CSF were less frequent than in the non-pretreated cases.     

Gallstones are associated with carotid atherosclerosis

Background/Aims: Gallstone disease (GD) and cardiovascular disease (CD) are common diseases worldwide with considerable economical impact and they are strongly associated. Carotid atherosclerosis is an excellent marker of risk for CD like stroke and myocardial infarction. The aim of this study was to assess the association between gallstones and carotid atherosclerosis. Methods: A cross‐sectional study was conducted. We evaluated subjects with ultrasonographical evidence of GD and asymptomatic subjects without such evidence. Anthropometric, clinical and biochemical variables were collected. The Metabolic syndrome was evaluated using adult treatment panel III criteria. Carotid artery intima–media thickness (CIMT) was determined by a standard ultrasound protocol. Insulin‐like growth factor‐1 (IGF‐1) serum levels were measured in all subjects. Results: We studied 191 subjects: 62 subjects with GD (53.2% males) and 129 asymptomatic subjects without GD (65.9% males). Subjects with GD exhibited a higher body mass index, body fat percent, insulin serum levels and CIMT (P<0.05 for all). The prevalence of GD was higher in subjects with a CIMT>0.75 independently of other factors [odds ratio (OR) 2.12, 95% confidence interval (CI) 1.04–4.34; P=0.039], and for every 0.1 mm increase in CIMT the independent probability to be a case of GD increased by a factor of 1.25 (95% CI 1.02–1.53; P=0.027). IGF‐1 levels did not differ among groups. Conclusions: Subjects with GD exhibit greater carotid atherosclerosis, and therefore have a higher risk for stroke and myocardial infarction.     

Percutaneous coronary intervention of or through saphenous vein grafts or internal mammary arteries: the impact of stents, adjunctive pharmacology, and multicomponent distal protection.

We hypothesized that the use of stents and aggressive adjunctive pharmacotherapies has been associated with lower rates of complicating myocardial infarction (MI) and improved long-term outcomes compared to either previous balloon-only percutaneous coronary intervention (PCI) or atheroablative intervention for lesions of or through saphenous vein grafts (SVGs) and/or internal mammary arteries (IMAs). PCI of SVG has been complicated by relatively high rates of procedural MI and less favorable long-term outcomes than native vessel PCI, stimulating the development and application of an array of technologies. This study was based on retrospective review of stent-era (1999-2004) 5-year experience of a single center with 95 SVG procedures in 85 patients and 20 IMA procedures in 20 patients. These cases were compared with the previously published experience of one of the operators during the balloon-only period and literature review of the application of multiple technologies to SVG intervention, as well as consideration of the reoperation alternative. There was one in-hospital death each in the SVG cohort (1%) and in the IMA cohort (5%). There were SIX procedural MIs (6%), defined by total CK > normal, and 19 procedural MIs (20%) based on troponin-I > 1.0. Follow-up has been from 4 months to 5 years (average, 2.5 years), with 91% survival and one late CABG in the IMA group. SVG PCI with stents and adjunctive pharmacotherapies is associated with relatively low rates of procedural MI and favorable long-term outcomes.