A. Tuttolomondo

Effects of losartan and delapril on the fibrinolytic system in patients with mild to moderate hypertension

AbstractBackground and objectives: Angiotensin-converting enzyme (ACE) probably influences the fibrinolytic system at a central point by converting angiotensin I to angiotensin II, which increases plasminogen activator inhibitor-1 (PAI-1) activity. This effect appears to be mediated in humans via the angiotensin II type 1 (AT1) receptor. The objective of this study was to evaluate, in patients with mild to moderate hypertension, the change in tissue plasminogen activator (t-PA) and PAI-1 plasma levels after treatment with an AT1-receptor blocker (losartan 50 mg/day) or an ACE inhibitor (delapril 60 mg/day).n Patients and methods: 30 hypertensive patients and 15 controls were enrolled. Essential hypertension was established by a medical history, physical examination and the absence of clinical findings suggestive of a secondary form of hypertension. Preliminary investigations, routine biochemical tests (including clearance of creatinine and oral glucose tolerance test), chest x-ray, standard and 24-hour ECG monitoring, M- and B-mode echocardiography and fundus oculi examinations were performed. No patients had previously received ACE inhibitors or AT1-receptor blockers. After a 14-day run-in period with placebo, patients were randomised in a double-blind fashion into two groups: 15 patients were randomised to losartan 50 mg/day (group 1), 15 patients were randomised to delapril 60 mg/day (group 2), and 15 healthy subjects were used as controls (group 3). Plasma PAI-1 and t-PA antigen were determined by enzyme-linked immunosorbent assay and a photometric method at the end of the run-in period and after 6 months of treatment.n Results: There were no significant differences among the three groups regarding age, sex, body mass index and smoking. After 6 months, both groups of patients showed a reduction in blood pressure values. The losartan group did not demonstrate significant changes in PAI-1 levels (96.52 ± 23.73 and 99.89 ± 22.18 μg/L, pre- and post-treatment, respectively) or in t-PA antigen levels (26.17 ± 6.18 and 27.32 ± 5.91 μ/L, pre- and post-treatment, respectively). The delapril group showed no significant changes in PAI-1 levels (97.73 ± 25.75 and 86.12 ± 13.12 μg/L, pre- and post-treatment, respectively), but did show a statistically significant difference (p < 0.005) in t-PA antigen levels (25.71 ± 6.40 and 32.24 ± 5.31 μg/L, pre- and post-treatment, respectively). The losartan group demonstrated significantly higher post-treatment PAI-1 values than the delapril group (p = 0.048).n Conclusion: The study showed that losartan does not affect fibrinolytic parameters, while delapril resulted in an insignificant reduction in PAI-1 and a significant increase in t-PA levels. Further studies are clearly required in order to establish whether these different effects on the fibrinolytic system between ACE inhibitors and AT1-receptor blockers may have clinical relevance.

Successful salvage therapy of intravenous cyclophosphamide for refractory polymyositis in an elderly patient: case report.

Dermatomyositis and polymyositis may affect children and adults and are now widely recognized as major causes of disability which, thanks to the introduction of immunosuppressive drugs, is often treatable, at least to some extent. Few data exist regarding polymyositis in elderly patients. We describe a case of refractory life-threatening polymyositis in an elderly patient, successfully treated with intravenous cyclophosphamide.

Microscopic Colitis as a Diagnosis to Consider by Clinicians and Pathologists Together: A Case Series and Review of Literature

Background: Microscopic colitis is a term used to define some clinical-pathological entities characterized by chronic watery diarrhea, normal radiological and endoscopic appearance, and microscopic abnormalities. nAim: In this article we report a personal case series of microscopic colitis in patients with different age and sex and symptomatic seriousness to better represent the heterogeneous clinical presentation of this type of disease, and a review of available literature data. nMethod:xa0 A definitive diagnosis of microscopic colitis is only possible by histological analysis. Specific histopathological findings, such as morphologically mild or moderate inflammation in the lamina propria, combined with either thickening of the sub-epithelial collagenous or lymphocytic attack on the surface epithelium, can be used to further classify these clinical entities as collagenous colitis (CC), lymphocytic colitis (LC), or other conditions. nResult: We presented a review of the most recents studies about microscopic colitis and we presented a case serie of four lymphocitic colitis and one collagenous colitis in patients with different age and sex and symptomatic seriousness to better represent the heterogeneous clinical presentation of this type of disease, and we also performed a brief review of available literature data analyzing epidemiology, pathogenesis, clinical presentation and therapy strategies of these group of colitis. nDiscussion: Clinicians should be able to provide elements of clinical suspicion to pathologists that could justify more specific histological evaluation that includes the assessment of the number of intraepithelial cells (IEL), and the thickness of the band of tissue collagen.

39 POLYMORPHISM OF PROINFLAMMATORY AND ANTI-INFLAMMATORY GENES IN PATIENTS WITH ACUTE ISCHEMIC STROKE

Backgrounds: the improvement in heart surgery and anaesthesiology techniques in last decades have improved morbility and mortality ratio also in high surgical risk patients. Enteral ischemia after heart surgery is a rare complication (0.2 2%), but carries significant mortality (70 100%): its incidence has not been changed in these years and cases reported in literature are even increased. Pathogenesis has not been clearly understood, being complex and multifactorial: the principal cause seems to be the reduction in cardiac outflow during operation. Splancnic atherosclerosis could be also implicated in worsening or favouring enteral ischemia. Actually no relevant articles have been yet published concerning splancnic vessels screening before heart surgery. Atherosclerosis extension is only assessed with carotid duplex ultrasound and anamnestic data about previous cardiovascular events. Scope: aims of the study were to evaluate duplex scanning utility and accuracy to identify atherosclerotic lesions in splancnic vessels and to relate them with other arterial districts involvement. Methods: we studied 91 patients previously subjected to coronary angiography before heart surgery (coronary by-pass, valvular prothesis or both) at “Centro Gallucci” of “Azienda Ospedaliera di Padova”. They were all investigated with echocolordoppler of carotid arteries, aorta and its principal branches, and lower limbs arteries: if some haemodinamic stenosis were found a second level (Angio-CT or Angio-NMR) exam was performed to confirm the previous one. Chi-square test was employed in statistical analysis comparing atherosclerotic lesions distribution. Results: prevalence of carotid lesions and peripheral arterial disease was major among patients with at least one coronary artery critical stenosis; this data was not related with the number of vessels involved. Superior mesenteric artery (SMA) plaques were four times more frequent in patients with critical coronaropaty: no patients without critical lesions in coronary arteries had a >70% SMA stenosis. Carotid plaques (>1.5mm thickness), in particular those >50%, were more frequently associated with critical lesions at coronary angiography, even more than intima-medial thickening (95% vs 45%). Among patients with any degree peripheral arterial disease (PAD), 72% had coronary critical stenosis versus 30% in patients without PAD; if haemodinamic stenosis were found in lower limb arteries the prevalence of coronary critical plaques were 95%. Patients with any carotid plaque had a 44% prevalence of SMA stenosis (whatever degree), while in patients without carotid lesions it was 12.5%. No one with unaffected lower limb arterial wall had atherosclerotic SMA involvement, while if PAD was present, there was a 40% prevalence of SMA plaques (any degree). From this study also stand out that in patients with carotid stenosis >50%, and mainly among those with PAD, splancnic vessels were involved more frequently then in people without them. Both carotid plaques and PAD had a 100% sensitivity to predict a critical stenosis at SMA, even if specificity was below 50%. Conclusions: abdominal vessels duplex scanning is indicated before heart surgery only when atherosclerotic plaques are found in carotid and lower limbs arteries. Finding that kind ok lesions in pre-surgery evaluation should suggest the operator to put to use all devices useful for preventing vascular complications in the splancnic district. Echocolordoppler, if performed by an export operator, could be useful to detect the presence of atherosclerotic plaques or abdominal aortic aneurisms in abdominal vessels.

Recurrent venous thromboembolism complicated by heparin-induced thrombocytopenia as a first manifestation of an occult cancer: a case report.

Heparin-Induced Trombocytopenia (HIT) is a serious and potentially fatal complication of patients on heparins. Its management is difficult and it can be more complicated in patients with cancer because of the hemorrhagic risk carried out by direct inhibitor of thrombin, the currently approved drug for HIT. At present, it is not clear whether cancer patients also have an increased risk of HIT. We describe the case of a patient with occult cancer at the moment of the index venous thrombosis, who developed Deep Vein Thrombosis (DVT) and concomitant HIT with thrombotic complications (recurrent contralateral venous thrombosis). The management of HIT was efficaciously based on the combined use of alternative antithrombotic regimens (Dermatan-Sulphate and Defibrotide), without an increased risk of bleeding. This case highlights the potential relationship between DVT, as first episode of an occult cancer, and the risk of developing HIT. The use of alternative antithrombotic therapy seems to be efficacious even in this high-risk cancer patient.

Different effects of losartan and delapril on plasma PAI-1 levels in patients with mild to moderate hypertension.

ACE probably influences the fibrinolytic system at acentral point by converting angiotensin I to angiotensin II,which increases PAI-1 activity. This effect appears to bemediated via the AT1-receptor in humans. The RAAS mayalso contribute to a reduction in t-PA production by degra-dation of bradykinin, since the latter increases the release ofprostacyclin, nitric oxide, and t-PA from endothelial cells.Accordingly, ACE inhibitors not only influence the fibrino-lytic system by a reduction of PAI-1 activity but also byincreasing t-PA activity [1–3]. However, few studies haveanalysed the effects of AT1-R antagonists on t-PA and PAI-1plasma levels and the in vivo effects of AT1-R antagonistson the fibrinolytic system are conflicting [4,5]. We checkedin patients with mild to moderate hypertension the change int-PA and PAI-1 plasma levels after treatment with an AT1-Rantagonist and after treatment with an ACE-in. Thirtypatients, after a 14 day run-in period with placebo, wererandomised (double blind) in two groups: Group 1 (15patients) received an AT1-R antagonist (losartan 50 mgonce a day), Group 2 (15 patients) received an ACE-in(delapril 60 mg/day); 15 healthy subjects were chosen ascontrols. The diagnosis of essential hypertension was estab-lished by history and physical examination and by theabsence of clinical findings suggestive of a secondary formof hypertension. During the recruitment period all thepatients were totally unselected, and preliminary investiga-tions included routine biochemical tests (including clearanceof creatinine and oral glucose tolerance test), chest X-ray,standardand24hECGmonitoring,M-andB-modeechocardiography and fundus oculi examination. Patientswith myocardial infarction (within 3 months of the study),chest pain, heart block, valvular disease and heart failure),renal failure, type 1 or 2 diabetes mellitus, electrolyteimbalances, moderate or severe Keith-Wegener hyperten-sive retinopathy, alcoholism or psychiatric problems, andpatients with concomitant left ventricular hypertrophy(echocardiography criteria) or with other target organ dam-age were excluded. Each patient gave informed consent. Nopatient had to have previously received ACE-in or AT1-Rantagonists. Ten millimetres of blood was withdrawn andcollected into acidified buffered citrate (biopool stabilyte fort-PA assays) and citrate (monovette for PAI-1 assays tubes)and kept on ice before being centrifuged at 2000 g for 30min at 4 jC. Platelet-free plasma was decanted and stored at 80 jC before assay. Plasma PAI-1 and t-PA antigen weredetermined by ELISA and a photometric method. All theassays were performed by blinded independent. PAI-1 and t-PA plasma levels were checked at the end of the run-inperiod and after 6 months of treatment with losartan (group1) or delapril (group 2), as well as the biochemical tests. Allthe data were expressed as mean valuesFS.D. and com-pared by paired t-test and Kruskal–Wallis test. Table 1shows the clinical data of all the groups. After 6 months oflosartan and delapril treatment, a significant blood pressurereduction was observed in both the groups. At baseline thegroups 1 and 2 displayed significantly higher levels of PAI-1 and t-PA antigen than the control group (Table 2). Sixmonths of losartan treatment was associated with no signif-icant changes in PAI-1 and t-PA antigen levels. On the