Serum concentrations of soluble intercellular adhesion molecule-1 and progress towards disease in patients infected with HIV

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell to cell adhesive interactions of the immune system. Concentrations of soluble ICAM-1 (s-ICAM-1) shed into the circulation were measured by a quantitative ELISA in HIV-infected persons without AIDS, patients with AIDS with or without evidence of acute opportunistic infection at the time of sampling, and HIV-seronegative patients with toxoplasmosis, community-acquired pneumonia, leishmaniasis and rickettsial infections. Patients were classified on the basis of clinical condition and CD4⁺ T-cell counts according to the 1993 revised HIV classification of the USA Centers for Disease Control. Concentrations of s-ICAM-1 in the serum of HIV-infected persons without AIDS-indicator conditions (categories A1, A2, B1 and B2) as well as in the serum of patients with AIDS (categories A3, B3, C1, C2 and C3) were significantly higher than normal (mean ± s.e.m. 469 ± 23, n = 60 and 780 ± 73, n = 56, respectively, versus 329 ± 15 ng/ml, P < 0·0001 and <0·0001 respectively) and differed also significantly from each other (P < 0·0001). Raised concentrations of s-ICAM-1 in the serum of afebrile patients with AIDS but without acute opportunistic infection at the time of sampling (mean ± s.e.m. 672 ± 76, n = 29) did not differ from those of the remaining patients with AIDS or from those of HIV-seronegative patients with the infections studied. A steady and significant increase of serum concentrations of s-ICAM-1 with progress of disease according to clinical category (categories A B C, p = 0·0007) as well as with the loss of circulating CD4⁺ T-cells (categories 1 2 3, p = 0·009) was observed. Individual serum concentrations of s-ICAM-1 showed negative correlations with individual total lymphocyte (P = 0·004), CD4⁺ T-cell (P = 0·05), CD8⁺ T-cell counts (P = 0·03) as well as positive correlation with serum concentrations of soluble interleukin-2 receptors (P < 0·0001), an indirect marker of progress of HIV-related disease. Serum concentrations of s-ICAM-1 did not differ between patients with AIDS who were receiving or not receiving zidovudine at the time of sampling. A longitudinal survey is needed in order to determine whether measuring serum concentrations of s-ICAM-1, although not specific, has any predictive or prognostic value in these patients as well as whether this bioactive molecule has any pathogenetic role in the progress of disease in HIV infection.     

Inverse relationship of hippocampal serotonin to avoidance behavior, serotonergic activation by emotional stress differentiated by estrous cycle and surgical stress.

The hippocampus is involved in learning, affect, and the neurobiology of stress. After recording individual emotional reactivity (ER) during handling for vaginal smear screening (VSS), serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), in the hypothalamus-preoptic area (HY-PA) and hippocampus were studied in two rat lines with different susceptibility to Freund's adjuvant arthritis (FAA), in relation to active avoidance behavior (AB), and under basal conditions in the FAA susceptible strain, in relation to ER, cycle stage and 20 h prior surgical stress. FAA susceptible rats compared to non-susceptible under equally low ER, showed higher AB, but lower 5-HIAA and 5-HIAA/5-HT ratio, under basal conditions, and upon termination of avoidance assay, only in hippocampus. In rats with different ER after prolonged VSS, high ER paralleled on diestrus-2 (DE-2), increased 5-HIAA and 5-HIAA/5-HT in the hippocampus and HY-PA, and adrenal weight, but decreased thymus and hippocampal weight. Under equal ER 5-HIAA and 5-HIAA/5-HT in the hippocampus and 5-HIAA/5-HT in the HY-PA were diminished on proestrus vs DE-2 but not estrus. Under equal distribution of proestrus and estrus higher ER paralleled higher hippocampal 5-HIAA. After equally high ER, combined with 20 h prior surgical stress, diminished hippocampal 5-HIAA/5-HT ratio, paralleled pronounced increase in adrenal weight compared to controls. Results suggest: negative association of hippocampal 5-HT to avoidance learning, a positive one to ER, modulated by cycle stage, and a role of differentiated 5-HT in homeostasis of HPA system.     

Adenocarcinoma of the gastric cardia: treatment via a left thoracoabdominal approach

We examined the outcome of adenocarcinomas of the gastric cardia treated by total or proximal gastrectomy, lower esophagectomy, and D2 lymphadenectomy via a left thoracoabdominal approach. We compare these results with those of other methods as well as review the literature. During a 10-year period (1991-2000) 180 patients with primary gastric cancer were admitted to our department. Thirty-six of the patients had adenocarcinoma of the cardia. Twenty-four patients underwent total gastrectomy, D2 lymphadenectomy, and esophagectomy, and four others underwent proximal gastrectomy and esophagectomy with esophagogastric anastomosis via a left thoracoabdominal approach. These latter 28 patients compose our study group. We had no operative mortality, the morbidity varied, and the quality of life and the loss of body weight ranged within satisfactory levels, but the survival rate was rather poor. The median survival time was 19 +/- 1.2 months. Survival was significantly longer in patients with less than 40 per cent positive resected lymph nodes (P = 0.035). From the resulting data and our experience we believe that the left thoracoabdominal approach gives excellent exposure for radical resection of cancer of the gastric cardia and should be the procedure of choice for curative resection of such tumors. This approach combined with total gastrectomy and D2 lymphadenectomy can be performed with an acceptably low mortality rate; it provides good palliation but not encouraging survival rates. Although it is less radical proximal gastrectomy gives the same results and a better quality of life but may be performed only in the early stages of the disease.     

Rituximab-induced B cell depletion in autoimmune diseases: potential effects on T cells

Peripheral B cell depletion strategies have been employed recently in the treatment of systemic autoimmune diseases and the initial clinical results have been encouraging. Although the major target of rituximab-based treatments was to reduce the levels of circulating autoantibodies, additional mechanisms of action may operate. Recent studies have addressed the question of potential effects of transient B cell depletion on other, non-B cell populations. The data, albeit uncontrolled, suggest that anti-CD20 monoclonal antibody treatment is associated with significant effects in the T cell pool, whereas individual clinical responses do not always correlate with changes in autoantibody titers. More specifically, it has been reported that rituximab administration may decrease the activated phenotype of peripheral and tissue-resident T cells by abolishing antigen presentation by B cells, and may enhance the numbers and function of regulatory T cells. In this review we analyze and discuss available data emerging from B cell depletion studies in patients with systemic lupus erythematosus, rheumatoid arthritis and other autoimmune conditions. Further controlled studies are needed to confirm the role of B cell depletion in modifying T cell function in vivo.     

24‐hour aortic blood pressure variability showed a stronger association with carotid damage than 24‐hour brachial blood pressure variability: The SAFAR study

We aim to compare 24‐hour aortic blood pressure variability (BPV) with brachial BPV in relation to carotid damage as estimated by carotid intima‐media thickness (CIMT) and cross‐sectional area (CCSA). Four hundred and forty five individuals received brachial and aortic 24‐hour ambulatory BP monitoring with a validated device (Mobil‐O‐Graph). Systolic BPV was estimated by average real variability (ARV) and time‐weighted standard deviation (wSD). In multiple logistic regression analysis, CIMT > 900 μm was significantly and independently associated with aortic ARV (OR = 1.38; 95% CI: 1.04‐1.84), aortic wSD (OR = 1.65; 95% CI: 1.19‐2.29) and brachial ARV (OR = 1.53; 95% CI: 1.07‐2.18), but not with brachial wSD. CCSA > 90th percentile was significantly and independently associated with aortic ARV (OR = 1.50; 95% CI: 1.07‐2.10) and wSD (OR = 1.70; 95% CI: 1.12‐2.56), but not with brachial BPVs. In receiver operator characteristics curve analysis, aortic wSD identified CCSA > 90th percentile better than brachial wSD (AUC: 0.73 vs 0.68, P < .01). In conclusion, aortic 24‐hour systolic BPV showed a slightly stronger association with carotid damage than brachial BPV.     

Edema and fibrosis imaging by cardiovascular magnetic resonance: How can the experience of Cardiology be best utilized in rheumatological practice?

Objectives

CMR, a non-invasive, non-radiating technique can detect myocardial oedema and fibrosis.

Method

CMR imaging, using T2-weighted and T1-weighted gadolinium enhanced images, has been successfully used in Cardiology to detect myocarditis, myocardial infarction and various cardiomyopathies.

Results

Transmitting this experience from Cardiology into Rheumatology may be of important value because: (a) heart involvement with atypical clinical presentation is common in autoimmune connective tissue diseases (CTDs). (b) CMR can reliably and reproducibly detect early myocardial tissue changes. (c) CMR can identify disease acuity and detect various patterns of heart involvement in CTDs, including myocarditis, myocardial infarction and diffuse vasculitis. (d) CMR can assess heart lesion severity and aid therapeutic decisions in CTDs.

Conclusion

The CMR experience, transferred from Cardiology into Rheumatology, may facilitate early and accurate diagnosis of heart involvement in these diseases and potentially targeted heart treatment.