Glycation of extracellular matrix proteins impairs migration of immune cells

The immune response during aging and diabetes is disturbed and may be due to the altered migration of immune cells in an aged tissue. Our study should prove the hypothesis that age and diabetes‐related advanced glycation end products (AGEs) have an impact on the migration and adhesion of human T‐cells. To achieve our purpose, we used in vitro AGE‐modified proteins (soluble albumin and fibronectin [FN]), as well as human collagen obtained from bypass graft. A Boyden chamber was used to study cell migration. Migrated Jurkat T‐cells were analyzed by flow cytometry and cell adhesion by crystal violet staining. Actin polymerization was determined by phalloidin‐Alexa‐fluor 488‐labeled antibody and fluorescence microscopy. We found that significantly fewer cells (50%, p = 0.003) migrated through methylglyoxal modified FN. The attachment to FN in the presence of AGE‐bovine serum albumin (BSA) was also reduced (p < 0.05). In ex vivo experiments, isolated collagen from human vein graft material negatively affected the migration of the cells depending on the grade of AGE modification of the collagen. Collagen with a low AGE level reduced the cell migration by 30%, and collagen with a high AGE level by 60%. Interaction of the cells with an AGE‐modified matrix, but not with soluble AGEs like BSA‐AGE per se, was responsible for a disturbed migration. The reduced migration was accompanied by an impaired actin polymerization. We conclude that AGEs‐modified matrix protein inhibits cell migration and adhesion of Jurkat T‐cells.     

Amelioration of lytic abnormalities of paroxysmal nocturnal hemoglobinuria with decay-accelerating factor.

Purified decay-accelerating factor (DAF), from the stroma of normal human erythrocytes, was incorporated into the membranes of erythrocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH), and its effect on the complement sensitivity of the cells was investigated. Reconstitution with exogenous DAF restored the ability of the affected PNH cells to resist assembly of the homologous C3 convertase, C4b2a, on their surfaces, and decreased the susceptibility of the cells to lysis in acidified serum. Conversely, treatment of normal erythrocytes with monoclonal or polyclonal anti-DAF antibodies abrogated the capacity of the normal cells to circumvent C4b2a assembly and rendered the cells sensitive to acid lysis. These findings show that the previously reported association of DAF deficiency with PNH is causally related to the lytic abnormalities of the cells and clarify the molecular basis for restriction of autologous convertase formation on normal human erythrocytes.     

Preoperative antibiotics and mortality in the elderly

OBJECTIVE AND BACKGROUND: It is generally thought that the use of preoperative antibiotics reduces the risk of postoperative infection, yet few studies have described the association between preoperative antibiotics and the risk of dying. The objective of this study was to determine whether preoperative antibiotics are associated with a reduced risk of death. METHODS: We performed a multivariate matched, population-based, case-control study of death following surgery on 1362 Pennsylvania Medicare patients between 65 and 85 years of age undergoing general and orthopedic surgery. Cases (681 deaths within 60 days from hospital admission) were randomly selected throughout Pennsylvania using claims from 1995 and 1996. Models were developed to scan Medicare claims, looking for controls who did not die and who were the closest matches to the previously selected cases based on preoperative characteristics. Cases and their controls were identified, and charts were abstracted to define antibiotic use and obtain baseline severity adjustment data. RESULTS: For general surgery, the odds of dying within 60 days were less than half in those treated with preoperative antibiotics within 2 hours of incision as compared with those without such treatment: (odds ratio = 0.44; 95% confidence interval, 0.32-0.60), P < 0.0001). For orthopedic surgery, no significant mortality reduction was observed (OR = 0.85; 95% confidence interval, 0.54-1.32; P < 0.464). INTERPRETATION: Preoperative antibiotics are associated with a substantially lower 60-day mortality rate in elderly patients undergoing general surgery. In patients who appear to be comparable, the risk of death was half as large among those who received preoperative antibiotics.     

Chlorambucil therapy in hairy cell leukemia: effects on lipid composition and lymphocyte subpopulations

Two patients with progressive hairy cell leukemia following splenectomy were treated with low-dose daily chlorambucil. Both had an objective hematologic response as determined by a return to normal hematocrit and platelet count. This was also reflected in the mononuclear cell fraction by the normalization of cholesterol content, cholesterol/phospholipid ratio, and the lymphocyte subpopulations. This article confirms previous reports on the efficacy of chlorambucil in this setting and describes some morphological, and biochemical concomitant events.     

Renal artery aneurysm as a cause of resistant hypertension in a young female--case report

A case of a 19-year-old woman suffering for 5 years from pharmacologically resistant hypertension, is presented. During invasive diagnostic procedures left renal artery aneurysm was found. Surgical resection with vessel prosthesis implantation was successfully performed. Examination carried-out 6 months later revealed good response to pharmacological treatment with normal levels of blood pressure.     

Intestinal pseudo-obstruction as an initial presentation of systemic sclerosis in two children

Two children are reported in whom intestinal pseudo-obstruction was the initial manifestation of systemic sclerosis. Gastrointestinal symptoms and skin changes resolved or improved in both children following treatment with prednisone and penicillamine (case 1) or methotrexate (case 2), although radiological changes of the gastrointestinal tract persisted at 3 and 2 yr of follow-up, respectively.