Mac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a functional unit on monocytic cells

The leukocyte integrin Mac-1 (CD11b/CD18) and the urokinase receptor (uPAR, CD87) mediate complementary functions in myelomonocytic cells. Both receptors promote degradation of fibrin(ogen) and also confer adhesive properties on cells because Mac-1 and uPAR bind fibrin and vitronectin, respectively. Staining of lung biopsy specimens from patients with acute lung injury indicated that fibrin and vitronectin colocalize at exudative sites in which macrophages bearing these receptors accumulate. Because of the parallel roles and physical proximity of Mac-1 and uPAR, the capacity of these receptors to functionally interact was explored. Induction of Mac-1 and uPAR expression on monocytic cell lines by transforming growth factor- beta 1 and 1.25-(OH)2 vitamin D3 conferred urokinase and uPAR-dependent adhesion to vitronectin, which was further promoted by engagement of Mac-1. Vitronectin attachment promoted subsequent Mac-1-mediated fibrinogen degradation threefold to fourfold. In contrast, enhancement of uPAR occupancy by exogenous urokinase or receptor binding fragments thereof inhibited Mac-1 function. Addition of urokinase progressively inhibited Mac-1-mediated fibrinogen binding and degradation (maximal inhibition, 91% +/- 14% and 72% +/- 15%, respectively). Saturation of uPAR with urokinase also inhibited binding of the procoagulant Mac-1 ligand, Factor X. These inhibitory effects of uPAR were reproduced in fresh monocytes, cultured monocytic cells, and in Chinese hamster ovary (CHO) cells transfected with both human Mac-1 and human uPAR. These data show that the procoagulant and fibrinolytic potential of monocytic cells is co-ordinately regulated by ligand binding to both Mac-1 and uPAR and identify uPAR as a regulator of integrin function. Vitronectin- enhanced fibrin(ogen) turnover by Mac-1 may operate as a salvage pathway in the setting of urokinase and plasmin inhibitors to promote clearance of the provisional matrix and subsequent healing.     

Fluoroscopic‐guided balloon dilatation and stenting in tracheal stenosis with metallic self‐expandable stents and long‐term follow‐up results

The purpose of this study was to assess the safety and long‐term efficacy of self‐expandable stents in the treatment of benign tracheal stenosis. Nine patients (seven men) with tracheal stenosis (including one with fistula) of varied cause were treated by fluoroscopically guided balloon dilatation and stenting with self‐expandable metallic stents. The procedure was carried out under topical spray in eight patients and under general anaesthesia in one patient. The patients were followed up for a period ranging between 13 and 60 months. In eight of the nine patients, satisfactory positioning of the stent was achieved at the first instance, with immediate relief of dyspnoea. One patient with innominate artery aneurysm died 16 days after the procedure because of renal failure. At 1 month of follow up, six out of eight (75%) of our live patients were without any respiratory embarrassment. This dyspnoea‐free result reached almost 90% by the end of 1 year especially so in the fibrous strictures. Four out of the eight live patients (50%) had cough for 2 months and two (25%) had mild blood‐tinged sputum treated by inhalation and mucolytic agents. Secondary intervention was required in one patient at 1 month because of recurrent symptoms. The patient with tracheo‐oesophageal fistula required surgical intervention because of fracture of the stent. Fluoroscopically guided balloon dilatation and stenting of the tracheal stenosis is an effective non‐surgical therapy resulting in cure of fibrous strictures and palliation in cases of malignancy.     

Different risk factors of microangiopathy in patients with Type I diabetes mellitus of short versus long duration. The EURODIAB IDDM Complications Study

Aims/hypothesis. To identify factors associated with early development of and late protection from microvascular complications in subjects with Type I (insulin-dependent) diabetes mellitus.¶Methods. The frequency of microvascular complications and their relation to risk factors were studied in 300 Type I diabetic subjects with short duration of disease ( ≤ 5 years) compared with 1062 subjects with long duration ( ≥ 14 years). Microvascular disease was defined as the presence of either retinopathy (assessed from centrally-graded retinal photographs) or urinary albumin excretion rate of more than 20 μg/min.¶Resu1ts. The prevalence of microvascular disease was 25 % in the short duration group. In the long duration group 18 % had no evidence of microvascular complications. In the short duration group factors associated with early development of complications were cigarette smoking and a family history of hypertension. Subjects free of microvascular complications in spite of long duration of diabetes had better glycaemic control, lower blood pressure, better lipid profile and lower von Willebrand factor levels.¶Conclusion/interpretation. At the early stages of Type I diabetes, cigarette smoking and genetic susceptibility to hypertension are important risk factors for microvascular complications. At a later stage, additional risk factors are poorer glycaemic control, higher blood pressure, and an unfavourable lipid profile possibly associated with endothelial dysfunction. Many of these factors are amenable to long-term intervention which should be started as soon as possible in the course of the disease. [Diabetologia (2000) 43: 348–355]     

Home blood pressure is as reliable as ambulatory blood pressure in predicting target-organ damage in hypertension

BACKGROUND: Our objective was to assess the value of home blood pressure (BP) monitoring in comparison to office BP measurements and ambulatory monitoring in predicting hypertension-induced target-organ damage. METHODS: Sixty-eight untreated patients with hypertension with at least two routine prestudy office visits were included (mean age, 48.6 +/- 9.1 [SD] years; 50 men). Office BP was measured in two study visits, home BP was measured for 6 workdays, and ambulatory BP was monitored for 24 h. All BP measurements were obtained using validated electronic devices. Target-organ damage was assessed by measuring the echocardiographic left-ventricular mass index (LVMI), urinary albumin excretion rate (AER) in two overnight urine collections, and carotid-femoral pulse-wave velocity (PWV) (Complior device; Colson, Garges-les-Gonesse, Paris, France). RESULTS: The correlation coefficients of LVMI with office BP were 0.24/0.15 (systolic/diastolic), with home BP 0.35/0.21 (systolic, P < .01), and with 24-h ambulatory BP 0.23/0.19, awake 0.21/0.16, and asleep 0.28/0.26 (asleep, both P < .05). The correlation coefficients of AER with office BP were 0.24/0.31 (diastolic, P < .05), with home BP 0.28/0.26 (both P < .05), and with 24-h ambulatory BP 0.25/0.24, awake 0.24/0.25 (diastolic, P < .05), and asleep 0.26/0.18 (systolic, P < .05). There was a trend for negative correlations between PWV and diastolic BP measurements (not significant). In multiple-regression models assessing independent predictors of each of the three indices of target-organ damage, systolic home BP and age were the only independent predictors of increased LVMI that reached borderline statistical significance. CONCLUSIONS: These data suggest that home BP is as reliable as ambulatory monitoring in predicting hypertension-induced target-organ damage, and is superior to carefully taken office measurements.