Ahmad Hamwi

Inflammatory response and myocardial injury following coronary artery bypass grafting with or without cardiopulmonary bypass.

OBJECTIVE In coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) the inflammatory response is suggested to be minimized. Coronary anastomoses are performed during temporary coronary occlusion. Inflammatory response and myocardial ischaemia need to be studied in a randomized study comparing CABG in multivessel disease with versus without CPB. METHODS Following randomization 30 consecutive patients received CABG either with (n=16) or without CPB (n=14). Primary study endpoints were parameters of the inflammatory response (interleukin (IL)-6, interleukin-10, ICAM-1, P-selectin) and of myocardial injury (myoglobin, creatine kinase-MB (CK-MB), troponin I) (intraoperatively, 4, 8, 16, 24 and 48 h after surgery). The secondary endpoint was clinical outcome. RESULTS The incidence of major (death: CABG with CPB n=1, not significant (n.s.)) and minor adverse events (wound infection: with CPB n=2, without CPB n=1, n.s. ; atrial fibrillation: with CPB n=3, without CPB n=2, n.s.) was comparable between both groups. The release of IL-6 was comparable during 8 h of observation (n.s.). Immediately postoperatively IL-10 levels were higher in the operated group with CPB (211.7+/-181.9 ng/ml) than in operated patients without CPB (104.6+/-40.3 ng/ml, P=0.0017). Thereafter no differences were found between both groups. A similar pattern of release was observed in serial measures of ICAM-1 and P-selectin, with no difference between both study groups (n.s.). Eight hours postoperatively the cumulative release of myoglobin was lower in operated patients without CPB (1829.7+/-1374. 5 microg/l) than in operated patients with CPB (4469.8+/-4525.7 microg/l, P=0.0152). Troponin I release was 300.7+/-470.5 microg/l (48 h postoperatively) in patients without CPB and 552.9+/-527.8 microg/l (P=0.0213). CK-MB mass release was 323.5+/-221.2 microg/l (24 h postoperatively) in operated patients without CPB and 1030. 4+/-1410.3 microg/l in operated patients with CPB (P=0.0003). CONCLUSIONS This prospective randomized study suggests that in low-risk patients the impact of surgical access on inflammatory response may mimic the influence of long cross-clamp and perfusion times on inflammatory response. Our findings indicate that multiregional warm ischaemia, caused by snaring of the diseased coronary artery, causes considerably less myocardial injury than global cold ischaemia induced by cardioplegic cardiac arrest.

Is Low Serum Bilirubin an Independent Risk Factor for Coronary Artery Disease in Men but Not in Women

For many years, the bile pigment bilirubin was considered to be only a toxic waste product formed during heme catabolism. Recent evidence, however, suggests that bilirubin acts as a potent physiologic antioxidant that may provide important protection against arteriosclerosis, coronary artery disease (CAD), and inflammation (1)(2)(3). The antioxidant capacity of bilirubin and its potent ability to scavenge peroxyl radicals have led to the concept that mildly increased circulatory bilirubin may have a physiologic function to protect against disease processes that involve oxygen and peroxyl radicals (4). Indeed, inverse correlations between the presence of CAD and total bilirubin concentrations in the circulation were reported recently in several independent studies (5)(6). Additionally, plasma bilirubin correlates inversely with several established risk factors for CAD, including smoking, increased LDL-cholesterol, diabetes, and obesity, but is directly proportional to the protective factor HDL-cholesterol (5)(7). The effect of bilirubin on the risk of cardiovascular disease is apparent in men (8) but is less clear in women (6)(9)(10). In the present study, we therefore examined the influence of gender on total bilirubin concentrations. All patients referred to the Department of Cardiology, University of Vienna, between August 1999 and September 2001 for whom clinical data were available were included in our study. Patients were divided in a CAD and a non-CAD group. The CAD group consisted of 544 patients (157 females and 387 males) with clinically relevant CAD. Clinically relevant CAD was defined as an exercise-induced ischemic ST-segment depression >0.1 mV (12%) (11) and/or a history of myocardial infarction (53%) or coronary intervention [coronary artery bypass (8%) or percutaneous transluminal coronary angioplasty (27%)]. In the non-CAD group (359 patients; 186 females and 173 males), the presence of CAD …

Cyclosporine Metabolism in Patients After Kidney, Bone Marrow, Heart-Lung, and Liver Transplantation in the Early and Late Posttransplant Periods

Cyclosporine is used in the prevention of allograft rejection. Owing to its narrow therapeutic index, regular monitoring of the whole blood levels of cyclosporine is required. We observed that immunoassays measured significantly higher cyclosporine levels than did high-performance liquid chromatography (HPLC) over time after transplantation. As cyclosporine metabolites cross-react even with immunoassays, this observation might be due to alterations of the cyclosporine metabolism. We analyzed cyclosporine metabolite concentrations in the early and in the late posttransplantation periods in 127 patients after kidney, bone marrow, heart-lung, and liver transplantation by HPLC and determined whole blood levels of cyclosporine by 4 immunoassays (enzyme-multiplied immunoassay [EMIT], cloned enzyme donor immunoassay [CEDIA], AxSYM [Abbott Laboratories, Chicago, IL], and TDx [Abbott Laboratories]). Despite reduced dose, we found significantly higher cyclosporine concentrations measured by the EMIT, AxSYM, and TDx assays in various patient groups. These results are due to the increased metabolite/cyclosporine ratio in the late posttransplantation period. In particular, the metabolites AM1 and AM19 increased significantly over time in bone marrow transplant recipients. Therefore, cyclosporine levels measured by immunoassays should be interpreted with caution.

The effect of calisthenic home exercises on postmenopausal fractures—a long-term observational study

OBJECTIVES To evaluate the long-term effects of calisthenic home exercises on the incidence of fractures in postmenopausal women. DESIGN Controlled long-term observational study. METHODS Postmenopausal women between 45 and 75 years of age who had been randomly assigned to an exercise or control group in the course of a previous study conducted 5-10 years ago, were invited for follow-up. The number of fractures before and during the observation time were recorded by means of a questionnaire. Vertebral deformities due to fractures were diagnosed by X-rays at entry and at follow-up. Walking speed, muscle strength, static posturography, and maximum oxygen uptake were measured in addition. RESULTS After an average follow-up time of 7.6+/-1.1 years, 73 women of the exercise group and 64 subjects of the control group were investigated. Thirty-three per cent (n=24) of the exercise group reported to have exercised continuously at least three times a week for 20 min. No intergroup differences between the compliant and non-compliant exercisers and the control group were seen in the number of fractures. However, the incidence of fracture was lowest in women with a baseline bone mass less than one standard deviation (SD) below the mean for young adults (high BMC) and highest in those with more than 2.5 SD below the mean for young adults (low BMC) (P<0.001, odds ratio 2.9 [95% CI, 1.59-5.39]). CONCLUSION This long-term follow-up did not produce any evidence that prescription of a calisthenic home exercise program may prevent fractures in postmenopausal women aged between 61+/-6.4 and 68+/-6.5 years.

Insulin, C-Peptide, and Restenosis after Femoral Artery Balloon Angioplasty in Type II Diabetic and Nondiabetic Patients

PURPOSE Endogenous and exogenous insulin is suggested to stimulate hypertrophic wound-healing responses and therefore may promote neointimal hyperplasia and restenosis after balloon angioplasty. The ratio of C-peptide to insulin reflects endogenous insulin secretion. In diabetic patients with insulin substitution, lower ratios display a higher proportion of exogenous insulin. The association and interaction of insulin and C-peptide with restenosis after percutaneous transluminal angioplasty (PTA) was investigated in type II diabetic and nondiabetic patients. MATERIALS AND METHODS The study group included 76 patients (median age, 68 years; interquartile range [IQR], 58-74 years; 55 men [72%]; 31 patients [41%] with type II diabetes) with intermittent claudication (n = 49; 64%) or critical limb ischemia (n = 27; 36%) who underwent primary successful femoral PTA. C-peptide and insulin levels were measured at baseline, and patients were followed to determine restenosis (> or =50%) at 12 months by color-coded duplex sonography. RESULTS Restenosis was found in 34 patients (45%) at 12 months. Patients with restenosis had higher insulin levels (median, 21.3 microU/mL IQR, 11.3-35.5 microU/mL) and a lower C-peptide/insulin ratio (median, 16; IQR, 10-21) compared with patients without restenosis (median insulin level, 11.6 microU/mL; IQR, 9.1-22.0 microU/mL [P = .008]; median ratio, 19 [IQR, 17-25], P = .039). In nondiabetic patients, insulin levels were significantly associated with restenosis (P = .046), whereas the ratio of C-peptide to insulin showed no association with restenosis. In patients with type II diabetes (n = 31; 41%), in contrast, the C-peptide/insulin ratio was associated with restenosis (P = .047), whereas insulin levels showed no significant association with restenosis (P = .14). CONCLUSIONS Insulin levels and the C-peptide/insulin ratio were associated with restenosis after femoral PTA. Exogenous and endogenous insulin may play a role in the pathogenesis of recurrent lumen loss after balloon angioplasty.

Markers of Bone Turnover in Postmenopausal Women Receiving Hormone Replacement Therapy

Abstract We investigated the effects of hormone replacement therapy (n = 27) on biochemical markers of bone turnover in a cross-sectional study of 127 postmenopausal women (according to WHO guidelines 18 patients had normal bone mineral density and 109 suffered from bone loss). Urinary excretion of free deoxypyridinoline and C- or N-telopeptide fragments of type I collagen served as bone resorption markers, serum osteocalcin as a bone formation marker. In women with no hormone replacement therapy, only C-and N-telopeptides correlated significantly with the lumbal T-score as an index for bone mineral density. Patients with bone loss receiving hormone replacement therapy exhibited significantly lower C-telopeptide, N-telopeptide and osteocalcin levels than those with no therapy (mean −45%, −43% and −26%, respectively), while deoxypyridinoline showed no significant differences. Among the markers investigated, C- and N-telopeptides seemed to be more reliable to detect therapeutic effects on bone metabolism. We present a preliminary model to evaluate bone turnover and resorption/formation rate.

Reference values for a heterogeneous ferritin assay and traceability to the 3rd International recombinant Standard for Ferritin (NIBSC code 94/572)

Abstract Reference values for Ferritin FlexTM on the Dimension RxL analyzer calibrated against the 3rd International Standard for Ferritin (recombinant) and N-Latex Ferritin ® on the BNA II nephelometer calibrated against the 2nd International Standard for Ferritin (spleen) both from Dade Behring (Marburg, Germany) were established (77 men and 182 women). Exclusion criteria were iron deficiency or iron deficiency anemia, inflammation, liver disease, malignancy, and other hematological or chronic disorders. The reference values (5.0th–95th percentiles) were as follow: for N-Latex Ferritin® –men, 12–399 μg/l; women <50 years, 11–102 μg/l and women ≥50 years, 17–219 μg/l; for Ferritin FlexTM –men, 14–415 μg/l; women <50 years, 11–111 μg/l and women ≥50 years, 22–224 μg/l. Both assays correlated very closely with each other (r=0.993). The linearity was acceptable down to 2 μg/l for the Ferritin FlexTM method, but only down to 15 μg/l for the N-Latex Ferritin® assay. The mean recovery of the 3rd International Standard by N-Latex Ferritin® and Ferritin FlexTM was comparable (~80%). We conclude that the new Ferritin FlexTM assay, which is based on the new 3rd International Standard, should be used for ferritin measurement in the routine medical laboratories in the future.