ACE gene polymorphism: a predictor of instent restenosis

Restenosis is the maladaptive response of the coronary artery to Restenosis occurs in 20-50% of patients [Pts] after balloon angioplasty and in 10-30% of patients receiving a stent. Neointimal proliferation is one distinct processes involved and the rennin-angiotensin system has been implicated in its pathogenesis. The level of plasma has been implicated in its pathogenesis. The level of plasma ACE is party under genetic control and the plasma and cellular levels pf ACE are associated with the insertion/deletion [I/D] polymorphism in the ACE gene where DD genotype bearers have higher levels of ACE than either ID or II genotype bearers. Aim: To assess the possible role of ACE gene polymorphism in the pathogenesis of instent restenosis [ISR]. We studies 136 patients having elective or emergency successful angioplasty and of a previously untreated native single coronary artery, including 117 males and 19 females, with a mean age of 52.5 +/- 9.8 years. Besides clinical evaluation, all pts were subjected to routine laboratory measurements, followed by DNA extraction for a peripheral venous sample using the QUIAmp Blood Kit. ACE gene was amplified by PCR-technique [30cycles], then were electrophoresed in agars gel and visualized directly with ethidium bromide staining under an ultraviolet light source to determine the ACE I/D genotypes. Clinical follow-up was performed on monthly basis up to six months for the occurrence of major adverse cardiac events. Angiographic follow-up was done in 93 patients at a mean of 6.17 +/- 2.3 months after PCI using edge detection and segment analysis by the Xcelera catch Philips Intruris QCA program to detect the minimal lumen diameter, reference vessel diameter and segment length before and after PCI and after 6 months follow up in the same views at baseline, to detect acute gain, late lumen loss and binary restenosis rate. ISR was expressed as >/= 50% diameter loss. Out of 136 pts, 93 were available for angiographic follow- up. Those were divided into two groups: 41 pts with angiographic evidence of restenosis [ISR], and 52pts without angiographic evidence of restenosis [NO-ISR]. The homozygous DD genotype was significantly more frequent in the ISR group compared to the NO-ISR group [51.2% vs 11.5%, p=0.005]. The heterozygous ID genotype was significantly more frequent in the NO-ISR group compared to the ISR group [76.9% vs 39%, p=0.005]. The homozygous II genotype was equal in both group [11.5% in ISR vs 9.8% in No ISR, p=0.79]. Compared to the heterozygous ID and the homozygous II, genotypes the homozygous DD genotype, of the ACE gene was more significantly associated with in-stent restenosis. This knowledge may help in the selection of subgroups of patients who will benefit form alternative therapeutic strategies such as CABG surgery or intensive preventive treatment or drug-eluting stent

Efficacy of recombinant human erythropoietin in critically ill anaemic septic patients

To investigate the erythropoietic response to high dose of a weekly dosing schedule of recombinant human erythropoietin [rHuEPO] in critically ill anaemic septic patients, and to determine whether the administration of rHuEPO would reduce the number of red blood cell [RBC] transfusions required and whether would affect clinical course and final outcome or not. A prospective, randomized, controlled single center study. Critical Care Department [medical/surgical ICU], Cairo University Hospital. A total of 60 patients who were admitted to the intensive care unit [ICU] and met the eligibility criteria were enrolled into the study [30 into the rHuEPO group, 30 into the control group]. Patients were randomized to receive either rHuEPO or not. The study drug [40.000 units of rHuEPO] was administrated by subcutaneous injection beginning on ICU day 2 and continued once weekly for a minimum of 2 doses or until ICU discharge [for patients with ICU length of stay >2 weeks] up to a total of 4 doses. CBC, reticulocytic count, iron variables, APACHE II, SOFA scores were measured at baseline and subsequently thereafter every 3rd day until ICU discharge or death or up to a total of 28 days. The EPO treated group showed significant increases in reticulocytic count compared with baseline [P<0.001] as well as with the control group [P<0.006]. The EPO-treated group exhibited also significant increases in Hb concentration compared with baseline [P<0.001] as well as with the control group [P<0.03]. All patients in the control group received RBC transfusion [100%] while only [83.33%] of the patients who received rHuEPO were transfused. Concerning the in hospital clinical course, the EPO treated group showed significant decreases in their APACHE II score during the study period compared with baseline [P<0.001] as well as with the control group [P<0.05], the EPO treated group showed also no significant difference in their SOFA score during the study period compared with baseline [P=0.923], however, the control group exhibited continous and significant increase in their SOFA score throughout the study period compared with baseline [P<0.003]. There was no significant difference in the final outcome [i.e. recovery, mortality or morbidity] [P:0.337, P: 0.286 respectively]. The administration of rHuEPO to critically ill anaemic septic patients is effective in raising their reticulocytic counts, Hb concentrations and in reducing the total number of units of RBCs they require. In addition there was a trend toward better inhospital clinical course, increased recovery and decreased mortality in rHuEPO group