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Jose Jayme G De Lima,1 Luis Henrique W Gowdak,1 Flavio J de Paula,1 Henrique Cotchi S Muela,2 Elias David-Neto,1 Luiz A Bortolotto1 1Heart Institute (InCor) and Renal Transplant Unit, Division of Urology, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, SP, Brazil; 2Department of Medicine, Agostinho Neto University Medical School, Luanda, Angola Background: Coronary artery disease (CAD) is prevalent in older patients on dialysis, but the prognostic relevance of coronary assessment in asymptomatic subjects remains undefined. We tested the usefulness of a protocol, based on clinical, invasive, and noninvasive coronary assessment, by answering these questions: Could selecting asymptomatic patients for coronary invasive assessment identify those at higher risk of events? Is CAD associated with a worse prognosis?Methods: A retrospective study including 276 asymptomatic patients at least 65 years old on the waiting list, prospectively evaluated for CAD and followed up until death or renal transplantation, were classified into two groups: 1) low-risk patients who did not undergo coronary angiography (n=63) and 2) patients who did undergo angiography (n=213). The latter group was reclassified into patients with significant CAD or normal angiograms/nonsignificant CAD.Results: CAD (≥70% stenosis) occurred in 124 subjects (58%). The incidence of death by any cause, coronary death, and major cardiovascular (CV) events were similar in patients selected or not for angiography and in those with or without significant CAD. Myocardial revascularization (surgical/percutaneous) was performed in only 21/276 patients (7.6%) and did not result in a reduction in mortality.Conclusion: In older patients on renal replacement therapy, the prevalence of CAD was high, but coronary investigation was not useful as a risk stratification tool and also resulted in a rather small proportion of patients eligible for intervention. Therefore, in the elderly, coronary investigation should not be considered routine in asymptomatic patients. Keywords: elderly, hemodialysis, coronary artery disease, kidney transplantation, cardiovascular, chronic kidney disease

Gabirobeira fruits are known for their rich nutrient content and bioactive phytochemical compounds that contribute to significant biological activities. Despite these attributes, the antioxidant potential and stability of phenolic compounds in gabiroba by-products after digestion have yet to be studied. The objective of this work was to evaluate the physical-chemical composition, antibacterial activity, α-amylase, and α-glucosidase inhibitory effects, as well as the in vitro digestibility of total phenolic compounds, total flavonoids, and antioxidant activity of powder and extract from gabiroba to valorize these byproducts. The gabiroba powder had low moisture, high carbohydrate and fiber content. The extraction using 80% ethanol demonstrated higher antioxidant, antibacterial, α-amylase, and α-glucosidase inhibition activities compared to the 12% ethanol and water extracts. Catechin and ferulic acid were the major phenolic compounds identified by HPLC-DAD. After digestion, both the powder and the gabiroba extract exhibited a bioaccessibility of more than 30% for total phenolic compounds and antioxidant activity during the gastric phase. However, the dry ethanol extract displayed higher total phenolic compounds after both the gastric and intestinal phases compared to the flour. Processing gabiroba into powder and extract is a promising approach to fully utilize this seasonal fruit, minimize waste, concentrate health-beneficial compounds, and valorize a by-product for use as a functional ingredient and raw material within the food and pharmaceutical industries., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To explore whether, in younger patients on dialysis with longer life expectancy, assessment of coronary artery disease (CAD) could identify individuals at higher risk of events and revascularization might improve outcomes in selected patients contrary to what had been observed in elderly patients., Methods: From August 1997 to January 2019, 2265 patients with stage 5 chronic kidney disease were prospectively referred for cardiovascular assessment. For this study, we selected 1374 asymptomatic patients aged between 18 and 64 years. After clinical risk stratification and cardiac scintigraphy by single-photon emission computed tomography, 866 patients underwent coronary angiography. The primary end point was the composite incidence of nonfatal/fatal major adverse cardiovascular events during a follow-up period of 0.1 to 189.7 months (median, 26 months). The secondary end point was all-cause mortality., Results: The primary end point occurred in 327 (23.8%) patients. Clinically stratified high-risk patients had a 3-fold increased risk of the primary end point. The prevalence of abnormal findings on perfusion scans was 29.2% (n=375), and significant CAD was found in 449 (51.8%) of 866 patients who underwent coronary angiography. An abnormal finding on myocardial perfusion scan and the presence of CAD were significantly associated with a 74% and 22% increased risk of cardiovascular events, respectively. In patients undergoing percutaneous coronary intervention or coronary artery bypass grafting (n=99), there was an 18% reduction in the risk of all-cause death relative to patients receiving medical treatment (P=.03)., Conclusion: In this cohort of middle-aged, asymptomatic patients on dialysis, assessment of CAD identified individuals at higher risk of events, and coronary intervention was associated with reducing the risk of death in selected patients., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

This study aimed to determine the nutritional components (macronutrients ans minerals) and α-amylase inhibition capacity of freeze-dried grumixama (Eugenia brasiliensis Lam) seeds (S) and pulp/peel (P) portions, at ripe and mid-ripe stages. In vitro digestion was also performed on S and P from grumixama to assess the bioaccessibility of total phenolic compound (TPC), flavonoids (TFC), and anthocyanins (TAC), as well as to examine their impact on antioxidant activity (DPPH, ABTS, FRAP). The ripening process impacts the bioactive compounds and individual phenolics of S and P portions. The ripe S was source of myricetin and exhibited higher antioxidant activity, while mid-ripe S was high in flavonoids and cinnamic acid with higher antiglycemic potential. Ripe P showed higher soluble fiber, carbohydrate, TAC, and caffeic acid content, whereas mid-ripe P had increased mineral content (calcium, potassium, manganese), catechin, and TPC. After in vitro digestion, the P portion showed a bioaccessibility of total phenolic content (TPC) and total flavonoid content (TFC) exceeding 40% at intestinal phase. In contrast, the S portions had better release of TPC and TFC and antioxidant activity at gastric phase. Considering the outstanding nutritional and biological properties of grumixama fruit, freeze-dried S and P portions from both ripening stages possess could be explored as valuable sources of nutrients and antioxidant compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The application of β-galactosidase in the fermentation of milk enables the acquirement of lower levels of lactose that are tolerated by lactose maldigesters and can reduce the nutritional consequences of avoiding dairy products. The present study evaluated the viability of the fortification of lactose-free prebiotic Greek yogurt formulas with whey protein concentrate (WPC). Two rotational central composite designs (RCCDs) were applied: one to perform the hydrolysis of the whey protein concentrate and another for the yogurt formulations (α = 2 with 2 central points and 4 axial points). Two β-galactosidase enzymes obtained from Kluyveromyces lactis were used. The content of lactose, glucose, galactose, and lactic acid were determined in the WPC, milk (pasteurized and powdered), and yogurts. The three best formulations regarding the attributes’ viscosity, syneresis, firmness, and elasticity were sensorially evaluated by using a nine-point hedonic scale. A microbiological analysis was performed after 48 h of yogurt production. The characterization of the products and the comparison of the results obtained were evaluated using the Student’s T test and the analysis of variance with Tukey’s test (p-values < 0.05). The application of a lactose-free WPC promoted viscosity, firmness, and elasticity. The syneresis was reduced, and whey increased the protein and calcium content. Lactose-free WPC can be used as a partial substitute for skimmed powdered milk in yogurts. The obtained results are encouraging with respect to the production of lactose-free Greek yogurts by the dairy industry.

In this research, the protein concentration, the permeate flux, and the predominant fouling mechanisms were investigated during ultrafiltration of different whey samples. The research was carried out at different values of transmembrane pressure and temperature using an experimental design, and a protein concentration of approximately 37 g L -1 was obtained for the bovine whey powder solution, at 60 kPa and 40 °C. The maximum flux observed was 8.9 and 7.9 kg m -2  h -1 , respectively, for the bovine whey powder solution and bovine whey, at 50 kPa and 30 °C. Although goat and buffalo whey presented lower permeate flux, probably due to high solutes and calcium contents, protein concentrates of around 40 g L -1 were obtained using the ultrafiltration process. This demonstrates the potential of ultrafiltration to obtain non-bovine protein concentrates. The best fit, verified by Ho and Zydney model, suggests that the fouling for all analyzed whey occurs due to pore blocking and subsequent deposit on the membrane surface., Competing Interests: Conflict of interestThe authors declare that there are no conflicts of interest., (© Association of Food Scientists & Technologists (India) 2020.)

Background: The value of coronary artery disease (CAD) assessment and coronary intervention in the prognosis of patients who undergo renal transplantation is controversial. We investigated whether pretransplant identification of patients with CAD is helpful for defining prognosis and whether preemptive coronary intervention reduces the incidence of cardiovascular events and death after engraftment., Methods: We analyzed the impact of coronary assessment by clinical stratification and coronary angiography and of coronary intervention on prognosis in 535 chronic kidney disease patients on the transplantation waiting list who underwent renal transplantation., Results: Patients with 70% or greater narrowing experienced more coronary events than patients with less significant lesions (P = 0.01) and subjects at low risk (P = 0.001). Coronary assessment did not discriminate between the risk of death in patients with or without significant CAD, and the independent predictors of death were age (hazards ratio, 1.04; 95% confidence interval, 1.01-1.06, P = 0.001) and diabetes (hazards ratio, 1.63; 95% confidence interval, 1.11-2.39, P = 0.01). No difference occurred in events and mortality between patients treated medically or by intervention, but the severity of CAD was higher in the latter., Conclusions: Coronary assessment identified patients at increased risk of posttransplant coronary events and was also useful to define a low-risk population that may be safely transplanted without in-depth cardiovascular evaluation. However, it did not differentiate between the risk of death in patients with and those without significant CAD. Survival was similar in patients undergoing either medical or interventional treatment for CAD.

Background. Acute kidney injury (AKI) is a common complication of cardiac surgery but its long-term consequences, in patients with chronic kidney disease (CKD), are not known. Methods. We compared the long-term prognoses of CKD patients who developed (n = 23) and did not develop (n = 35) AKI during the period of hospitalization after undergoing coronary artery bypass graft (CABG). Fifty-eight patients who survived (69.6 ± 8.4 years old, 72% males, 83% Whites, 52% diabetics, baseline GFR: 46 ± 16 mL/min) were followed up for 47.8 ± 16.4 months and treated for secondary prevention of events. Results. There were 6 deaths, 4 in the AKI+ and 2 in the AKI- group (Log-rank = 0.218), two attributed to CV causes. At the end of the study, renal function was similar in the two groups. One AKI- patient was started on dialysis. Only 4 patients had an increase in serum creatinine ≥ 0.5 mg/dL during follow-up. Conclusion. CKD patients developing AKI that survived the early perioperative period of coronary intervention present good renal and nonrenal long-term prognosis, compared to patients who did not develop AKI.

Background: Kaurenoic acid (KA), a diterpene extracted from copaíba oil-resin, is known to have potent antioxidant and anti-inflammatory properties. L-Arginine (LA) is an amino acid and a nitrogenous precursor for the synthesis of nitric oxide (NO). NO paper in wound healing has already been well documented. The aim of this study was to investigate the protective effects of LA and KA against ischemia reperfusion injury in a randomized skin flap model in rats., Methods: A modified McFarlane flap model measuring 2.5 wide × 8 cm long was established in 36 anesthetized rats and evaluated within 3 groups: group control, group L-arginine, and group kaurenoic acid. Each group was subdivided into two subgroups (T1 and T2, n = 6 each). Samples were collected 24 h (T1)/48 h (T2) postoperatively for oxidative stress (glutathione), as non-protein thiols, malondialdehyde (MDA), NO2, inflammation [myeloperoxidase (MPO)], and cytokines TNF-α and IL-1β assays., Results: KA promoted a significant decrease of TNF-α and IL-1 expression and MPO activity at T1/T2 time points. NSGH levels increased significantly in KA-treated rats, while MDA levels decreased significantly in the same rats. Arginine promoted a significant decrease in MDA levels at the T1 time point and a significant increase in non-protein thiols concentrations at T1/T2 time points. NO2 concentration also decreased at the T1 time point., Conclusions: KA may attenuate the oxidative stress and the inflammation, thereby reducing tissue damage induced by ischemia/reperfusion in rats subjected to dorsal skin flaps., No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

We examined the impact of obesity (BMI ≥30 kg/m(2) , n = 357) on prognosis in 1696 hemodialysis (HD) patients before and after renal transplantation (TX). End-points were coronary events, composite cardiovascular (CV) events, and death. Obese HD patients were older (55.9 ± 9.2 vs. 54.2 ± 11), had more diabetes (54% vs. 40%), dyslipidemia (49% vs. 30%), altered myocardial scan (38% vs. 31%), myocardial infarction (MI) (16% vs. 10%), coronary intervention (11% vs. 7%), higher total cholesterol (186 ± 52 vs. 169 ± 47), and triglycerides (219 ± 167 vs. 144 ± 91). Obese undergoing TX had more dyslipidemia (46% vs. 31%), angina (23% vs. 14%), MI (18% vs. 5%), increased total cholesterol (185 ± 56 vs. 172 ± 48), and triglycerides (237 ± 190 vs. 149 ± 100). Obesity was independently associated with coronary events (log-rank = 0.008, HR 2.55% CI 1.27-5.11) and death (log-rank 0.046, HR 1.52, % CI 1.007-2.30) in TX but not in HD. Obese HD patients had more risk factors and ischemic heart disease, but these characteristics did not interfere with prognosis. In TX patients, obesity predicts coronary events and death., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background. High serum uric acid (UA) is associated with increased cardiovascular (CV) risk in the general population. The impact of UA on CV events and mortality in CKD is unclear. Objective. To assess the relationship between UA and prognosis in hemodialysis (HD) patients before and after renal transplantation (TX). Methods. 1020 HD patients assessed for CV risk and followed from the time of inception until CV event, death, or TX (HD) or date of TX, CV event, death, or return to dialysis (TX). Results. 821 patients remained on HD while 199 underwent TX. High UA (≥428 mmol/L) was not associated with either composite CV events or mortality in HD patients. In TX patients high UA predicted an increased risk of events (P = 0.03, HR 1.6, and 95% CI 1.03-2.54) but not with death. In the Cox proportional model UA was no longer significantly associated with CV events. Instead, a reduced GFR (<50 mL/min) emerged as the independent risk factor for events (P = 0.02, HR 1.79, and % CI 1.07-3.21). Conclusion. In recipients of TX an increased posttransplant UA is related to higher probability of major CV events but this association probably caused concurrent reduction in GFR.

Background: The renoprotective effect of N-acetylcystein in patients undergoing coronary artery bypass graft surgery is controversial., Methods: We assessed the renoprotective effect of the highest dose of N-acetylcystein sanctioned for clinical use in a prospective, double-blind, placebo-controlled study including 70 chronic kidney disease patients, stage 3 or 4, who underwent coronary artery bypass graft surgery, on cardiopulmonary bypass (CPB) and off CPB, and were randomly allocated to receive either N-acetylcystein 150 mg/kg followed by 50 mg/kg for 6 hours in 0.9% saline or only 0.9% saline. Acute kidney injury was defined by the Acute Kidney Injury Network classification., Results: The incidence of kidney injury was reduced in the N-acetylcystein group (57.1% versus 28.6%, p=0.016). Nonuse of N-acetylcystein (relative risk 3.58, 95% confidence interval: 1.04 to 12.33, p=0.04) and cardiopulmonary bypass (relative risk 4.55, 95% confidence interval: 1.28 to 16.15, p=0.02) were independent predictors of kidney injury. In patients treated with CPB, N-acetylcystein reduced the incidence of kidney injury from 63% to 46%. Oxidative stress was increased in control subjects (p=0.01) and abolished in patients receiving N-acetylcystein., Conclusions: Maximum intravenous doses of N-acetylcystein reduce the incidence of acute kidney injury in patients with kidney disease undergoing coronary artery bypass graft surgery, abolish oxidative stress, and mitigate the negative effect of CPB on renal function., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Renal transplant candidates are at high risk of coronary artery disease (CAD). We sought to develop a new risk score model to determine the pre-test probability of the occurrence of significant CAD in renal transplant candidates., Methods: A total of 1,060 renal transplant candidates underwent a comprehensive cardiovascular risk evaluation. Patients considered at high risk of CAD (age ≥50 years, with either diabetes mellitus (DM) or cardiovascular disease (CVD)), or having noninvasive testing suggestive of CAD were referred for coronary angiography (n = 524). Significant CAD was defined by the presence of luminal stenosis ≥70%. A binary logistic regression model was built, and the resulting logistic regression coefficient B for each variable was multiplied by 10 and rounded to the next whole number. For each patient, a corresponding risk score was calculated and the receiver operating characteristic (ROC) curve was constructed., Results: The final equation for the model was risk score = (age × 0.4) + (DM × 9) + (CVD × 14) and for the probability of CAD (%) = (risk score × 2) - 23. The corresponding ROC for the accuracy of the diagnosis of CAD was 0.75 (P <0.0001) in the developmental model., Conclusions: We developed a simple clinical risk score to determine the pre-test probability of significant CAD in renal transplant candidates. This model may help those directly involved in the care of patients with end-stage renal disease being considered for transplantation in an attempt to reduce the rate of cardiovascular events that presently hampers the long-term prognosis of such patients.

In hypertensive patients with indication of renal arteriography to investigate renal artery stenosis (RAS) there are no recommendations regarding when to investigate coronary artery disease (CAD). Moreover, the predictors of CAD in patients with RAS are not clear. We aimed to evaluate the frequency and the determinants of CAD in hypertensive patients referred to renal angiography. Eighty-two consecutive patients with high clinical risk suggesting the presence of RAS systematically underwent renal angiography and coronary angiography during the same procedure. Significant arterial stenosis was defined by an obstruction ≥ 70% to both renal and coronary territories. Significant CAD was present in 32/82 (39%) and significant RAS in 32/82 (39%) patients. Both CAD and RAS were present in 25.6% from the 82 patients. Patients with severe CAD were older (63 ± 12 vs. 56 ± 13 years; p = 0.03) and had more angina (41 vs. 16%; p = 0.013) compared to patients without severe CAD. Significant RAS was associated with an increased frequency of severe CAD compared to patients without significant RAS (66% vs. 22%, respectively; p<0.001). Myocardial scintigraphy showed ischemia in 21.8% of the patients with CAD. Binary logistic regression analysis showed that RAS ≥ 70% was independently associated with CAD ≥ 70% (OR: 11.48; 95% CI 3.2-40.2; p<0.001), even in patients without angina (OR: 13.48; 95%CI 2.6-12.1; p<0.001). Even considering a small number of patients with significant RAS, we conclude that in hypertensive patients referred to renal angiography, RAS ≥ 70% may be a strong predictor of severe CAD, independently of angina, and dual investigation should be considered.

Background: We evaluated whether the advantages conferred by renal transplantation encompass all individuals or whether they favor more specific groups of patients., Methods: One thousand and fifty-eight patients on the transplant waiting list and 270 receiving renal transplant were studied. End points were the composite incidence of CV events and death. Patients were followed up from date of placement on the list until transplantation, CV event, or death (dialysis patients), or from the date of transplantation, CV event, return to dialysis, or death (transplant patients)., Results: Younger patients with no comorbidities had a lower incidence of CV events and death independently of the treatment modality (log-rank=0.0001). Renal transplantation was associated with better prognosis only in high-risk patients (p=0.003)., Conclusions: Age and comorbidities influenced the prevalence of CV complications and death independently of the treatment modality. A positive effect of renal transplantation was documented only in high-risk patients. These findings suggest that age and comorbidities should be considered indication for early transplantation even considering that, as a group, such patients have a shorter survival compared with low-risk individuals., (© 2012 John Wiley & Sons A/S.)

Background: The usefulness of stress myocardial perfusion scintigraphy for cardiovascular (CV) risk stratification in chronic kidney disease remains controversial. We tested the hypothesis that different clinical risk profiles influence the test., Methods: We assessed the prognostic value of myocardial scintigraphy in 892 consecutive renal transplant candidates classified into four risk groups: very high (aged≥50 years, diabetes and CV disease), high (two factors), intermediate (one factor) and low (no factor)., Results: The incidence of CV events and death was 20 and 18%, respectively (median follow-up=22 months). Altered stress testing was associated with an increased probability of cardiovascular events only in intermediate-risk (one risk factor) patients [30.3 versus 10%, hazard ratio (HR)=2.37, confidence interval (CI) 1.69-3.33, P<0.0001]. Low-risk patients did well regardless of scan results. In patients with two or three risk factors, an altered stress test did not add to the already increased CV risk. Myocardial scintigraphy was related to overall mortality only in intermediate-risk patients (HR=2.8, CI 1.5-5.1, P=0.007)., Conclusions: CV risk stratification based on myocardial stress testing is useful only in patients with just one risk factor. Screening may avoid unnecessary testing in 60% of patients, help stratifying for risk of events and provide an explanation for the inconsistent performance of myocardial scintigraphy.

We present a review of current strategies for the diagnosis and treatment of coronary artery disease (CAD) in patients with advanced chronic kidney disease who are on the waiting list for transplants, based on data from the literature and originated from a single-center cohort of 1,250 patients with maximum follow-up of 12 years. We discuss the best way to select patients to be tested for CAD, how to choose the more adequate screening test for CAD and cardiovascular disease, how to select patients for invasive treatment studies and how to treat patients with significant CAD. We also suggest new research avenues to be explored to resolve some problems in this area.

Deep lymphatic drainage plays an important role in the lung, as it removes foreign materials laying on the airways surface, such as pathogenic microorganisms. This drainage is also associated with lung tumour dissemination route. Liposomes with a specially tailored membrane were used as foreign particles to be removed by the lung lymphatics. We aim to obtain images of deep lung lymphatics in baboons using liposomes encapsulating (99m)Tc-HMPAO, as aerosols. Axillary lymph nodes were visualized 30 min post-inhalation, becoming more evident 1 hour after, when abdominal aortic and inguinal lymph nodes were also observed. Late images added no additional information. ROI's and their time-activity curves were drawn to obtain biokinetic information. In conclusion, we can say that the proposed technique enables visualization of the deep lymphatic lung network and lymph nodes. This methodology may be an important tool for targeted lung delivery of cytotoxic drugs., (Copyright © 2011. Published by Elsevier España.)

Background: The incidence of unexplained sudden death (SD) and the factors involved in its occurrence in patients with chronic kidney disease are not well known., Methods: We investigated the incidence and the role of co-morbidities in unexplained SD in 1139 haemodialysis patients on the renal transplant waiting list., Results: Forty-four patients died from SD of undetermined causes (20% of all deaths; 3.9 deaths/1000 patients per year), while 178 died from other causes and 917 survived. SD patients were older and likely to have diabetes, hypertension, past/present cardiovascular disease, higher left ventricular mass index, and lower ejection fraction. Multivariate analysis showed that cardiovascular disease of any type was the only independent predictor of SD (P = 0.0001, HR = 2.13, 95% CI 1.46-3.22). Alterations closely associated with ischaemic heart disease like angina, previous myocardial infarction and altered myocardial scan were not independent predictors of SD. The incidence of unexplained SD in these haemodialysis patients is high and probably a consequence of pre-existing cardiovascular disease., Conclusions: Factors influencing SD in dialysis patients are not substantially different from factors in the general population. The role played by ischaemic heart disease in this context needs further evaluation.

Unlabelled:  , Background: The best strategy for pre-transplant investigation and treatment of coronary artery disease (CAD) is controversial., Methods: We evaluated 167 renal transplant recipients before transplantation to determine the incidence of cardiac events and death. We performed clinical evaluations and myocardial scans in all patients and coronary angiography in select patients., Results: Asymptomatic patients with normal myocardial scans (n=57) had significantly fewer cardiac events (log-rank=0.0002) and deaths (log-rank=0.0005) than did patients with abnormal scans but no angiographic evidence of CAD (n=76) and individuals with CAD (n=34) documented angiographically. CAD increased the probability of events (HR=2.27, % CI 1.007-5.11; p=0.04). The incidence of cardiac events (log-rank=0.349) and deaths (log-rank=0.588) was similar among patients treated medically (n=23) or by intervention (n=11)., Conclusion: Asymptomatic patients with normal myocardial scans had a better cardiac prognosis than did patients with or without CAD and positive for myocardial ischemia. Patients with altered scan and CAD had the poorer outcome. Guideline-oriented medical treatment is safe and yields results comparable to coronary intervention in renal transplant patients with CAD. The data do not support preemptive myocardial revascularization for renal transplant candidates., (© 2009 John Wiley & Sons A/S.)

Background: We tested the hypothesis that the universal application of myocardial scanning with single-photon emission computed tomography (SPECT) would result in better risk stratification in renal transplant candidates (RTC) compared with SPECT being restricted to patients who, in addition to renal disease, had other clinical risk factors., Methods: RTCs (n=363) underwent SPECT and clinical risk stratification according to the American Society of Transplantation (AST) algorithm and were followed up until a major adverse cardiovascular event (MACE) or death., Results: Of the 363 patients, 79 patients (22%) had an abnormal SPECT scan and 270 (74%) were classified as high risk. Both methods correctly identified patients with increased probability of MACE. However, clinical stratification performed better (sensitivity and negative predictive value 99% and 99% vs. 25% and 87%, respectively). High-risk patients with an abnormal SPECT scan had a modest increased risk of events (log-rank = 0.03; hazard ratio [HR] = 1.37; 95% confidence interval [95% CI], 1.02-1.82). Eighty-six patients underwent coronary angiography, and coronary artery disease (CAD) was found in 60%. High-risk patients with CAD had an increased incidence of events (log-rank = 0.008; HR=3.85; 95% CI, 1.46-13.22), but in those with an abnormal SPECT scan, the incidence of events was not influenced by CAD (log-rank = 0.23). Forty-six patients died. Clinical stratification, but not SPECT, correlated with the probability of death (log-rank = 0.02; HR=3.25; 95% CI, 1.31-10.82)., Conclusion: SPECT should be restricted to high-risk patients. Moreover, in contrast to SPECT, the AST algorithm was also useful for predicting death by any cause in RTCs and for selecting patients for invasive coronary testing.

Background: We assessed the results of a noninvasive therapeutic strategy on the long-term occurrence of cardiac events and death in a registry of patients with chronic kidney disease (CKD) and coronary artery disease (CAD)., Methods: We analyzed 519 patients with CKD (56+/-9 years, 67% men, 67% whites) on maintenance hemodialysis with clinical or scintigraphic evidence of CAD by using coronary angiography., Results: In 230 (44%) patients, coronary angiography revealed significant CAD (lumen reduction > or =70%). Subjects with significant CAD were kept on medical treatment (MT; n=184) or referred for myocardial revascularization (percutaneous transluminal coronary angioplasty/coronary artery bypass graft-intervention; n=30) according to American College of Cardiology/American Heart Association guidelines. In addition, 16 subjects refused intervention and were also followed-up. Event-free survival for patients on MT at 12, 36, and 60 months was 86%, 71%, and 57%, whereas overall survival was 89%, 71%, and 50% in the same period, respectively. Patients who refused intervention had a significantly worse prognosis compared with those who actually underwent intervention (events: hazard ratio=4.50; % confidence interval=1.48-15.10; death: hazard ratio=3.39; % confidence interval 1.41-8.45)., Conclusions: In patients with CKD and significant CAD, MT promotes adequate long-term event-free survival. However, failure to perform a coronary intervention when necessary results in an accentuated increased risk of events and death.

Objective: The purposes of this study were to use the myocardial delayed enhancement technique of cardiac MRI to investigate the frequency of unrecognized myocardial infarction (MI) in patients with end-stage renal disease, to compare the findings with those of ECG and SPECT, and to examine factors that may influence the utility of these methods in the detection of MI., Subjects and Methods: We prospectively performed cardiac MRI, ECG, and SPECT to detect unrecognized MI in 72 patients with end-stage renal disease at high risk of coronary artery disease but without a clinical history of MI., Results: Fifty-six patients (78%) were men (mean age, 56.2 +/- 9.4 years) and 16 (22%) were women (mean age, 55.8 +/- 11.4). The mean left ventricular mass index was 103.4 +/- 27.3 g/m(2), and the mean ejection fraction was 60.6% +/- 15.5%. Myocardial delayed enhancement imaging depicted unrecognized MI in 18 patients (25%). ECG findings were abnormal in five patients (7%), and SPECT findings were abnormal in 19 patients (26%). ECG findings were false-negative in 14 cases and false-positive in one case. The accuracy, sensitivity, and specificity of ECG were 79.2%, 22.2%, and 98.1% (p = 0.002). SPECT findings were false-negative in six cases and false-positive in seven cases. The accuracy, sensitivity, and specificity of SPECT were 81.9%, 66.7%, and 87.0% (not significant). During a period of 4.9-77.9 months, 19 cardiac deaths were documented, but no statistical significance was found in survival analysis., Conclusion: Cardiac MRI with myocardial delayed enhancement can depict unrecognized MI in patients with end-stage renal disease. ECG and SPECT had low sensitivity in detection of MI. Infarct size and left ventricular mass can influence the utility of these methods in the detection of MI.

Background: Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved., Methods: We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events., Results: After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51)., Conclusions: In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.), (2009 Massachusetts Medical Society)

Unlabelled: Lung deep lymphatic drainage (LDLD) plays an important role in the removal of foreign materials from lungs being alveolar macrophages the first line of phagocytic defence with high affinity for pathogenic microorganisms. Bacillus subtilis is a well-known genome- decoded saprophyte of the human respiratory tract used in research and in the biotechnology industry. Lung deep lymphatic chains (LDLC) constitute one of the first sites of lung tumours' dissemination. In this work we intended to develop and validate a non-invasive method for assessing LDLC by nanoradioliposomes aerosolised modulated on the Bacillus subtilis spore wall. The final goal was to produce a nanoradioliposome formulation that can mimics the dynamics of preferential removal of spores by LDLD and present the ideal properties as a tracer for molecular imaging studies. Seven different liposomal formulations were tested, and the formulation-F demonstrated physicochemical and radiopharmaceutical properties that make it an ideal candidate as an in vivo probe for molecular imaging studies of the LDLC. Nanoradioliposomes of the formulation-F after labelling with 99mTc-HMPAO were administered as aerosols to 20 Sus scrofa. Hilar and interpulmonary communications were visualized in first 5 minutes post-inhalation, infradiaphragmatic chains between 10 and 20 minutes, the ganglia of the aortic chain at 20 minutes and those of the renal hilar region at 30 minutes., Conclusion: the proposed method enables visualization of deep lymphatic lung network and lymph nodes. Besides, this technique involving the modulation of nanoradioliposomes targeting specific organs or tissues may be an important tool for diagnostic or even for therapeutic purposes.

Background: Renal transplant candidates are at an increased risk for coronary artery disease (CAD), a strong predictor of cardiovascular events [major adverse coronary events (MACE)]. Coronary angiography is a costly, risky, invasive procedure. We sought to determine clinical predictors of significant CAD (stenosis > or =70%) in high-risk renal transplant candidates., Methods: Clinical evaluation and coronary angiography were performed in 301 patients (57+/-8 years, 73% men) on hemodialysis for 32 months (median). Patients were followed-up for 22 months (median). Inclusion criteria were diabetes (type 1 or 2), evidence of cardiovascular disease, or age > or =50 years. Risk factors included hypertension (93.7%), overweight/obesity (54.3%), dyslipidemia (44.9%), diabetes (42.1%), and smoking (24.3%). Cardiovascular disease was found as follows: peripheral arterial disease (PAD) (31.2%), angina (28.1%), stroke (12.9%), myocardial infarction (MI) (10.3%), and heart failure (9.3%)., Results: Significant CAD was found in 136 individuals (45.2%). Diabetes [odds ratio (OR)=1.82; 95% confidence interval (CI)=1.08-3.07], PAD (OR=2.50; 95% CI=1.44-4.37), and previous MI (OR=7.75; 95% CI=3.03-23.98) were associated with significant CAD. The prevalence of significant CAD increased with the number of clinical predictors from 26% (none) to 100% (all present) (P<0.0001). The incidence of fatal/nonfatal MACE increased two, four, and sixfold in those with diabetes, PAD, or previous MI, respectively (P<0.0001)., Conclusions: In high-risk patients with end-stage renal disease, the prevalence of CAD and the incidence of MACE were high. Significant CAD or cardiovascular complications were not related to the majority of classic risk factors. Patients with diabetes, PAD, or previous MI are at higher risk of CAD, MACE, or both and, thus, must be referred for invasive diagnostic procedures.

Background: Secondary hyperparathyroidism (SHPT) and its associated abnormalities in mineral metabolism increase the risk of cardiovascular morbidity and death in chronic renal failure (CRF). The effect of parathyroidectomy (PTX) on the incidence of major cardiovascular events in CRF patients with SHPT is unknown. We tested the hypothesis that PTX reduces the incidence of cardiovascular complications and death in CRF patients with severe SHPT scheduled for PTX, comparing the outcome of patients treated or not treated by PTX., Methods: The study comprised 118 CRF patients with SHPT on maintenance hemodialysis, unresponsive to medical treatment and scheduled for PTX. Patients underwent comprehensive cardiovascular evaluations at baseline. They were followed up until death, occurrence of major cardiovascular events, or kidney transplantation., Results: No deaths related to PTX occurred. After a median follow-up of 30 months, 50 patients (42%) had undergone PTX whereas 68 (58%) had not. The groups were comparable in terms of age, sex, race, serum parathyroid hormone, calcium or phosphate, calcium x phosphate product, and all major cardiovascular variables, except diastolic blood pressure. PTX was associated with a reduced incidence of major cardiovascular events (P = .02) and overall mortality (P

Background: In renal transplant candidates (RTC), diabetes and coronary artery disease (CAD) are commonly observed. However, whether diabetes imparts a cardiovascular risk equivalent to that of CAD and whether CAD adds to the cardiovascular risk associated with diabetes is unknown., Methods: To assess the interplay between diabetes and CAD as a determinant of major adverse cardiovascular events (MACE), 288 high-risk RTC (56.4+/-8.1 years old, 72% males) underwent a comprehensive cardiovascular evaluation including coronary angiography. Patients were divided into four groups based on the diagnoses of diabetes and CAD (>70% narrowing), and followed up for 1-60 months (median, 17). The primary endpoint was the composite incidence of fatal/non-fatal MACE., Results: During follow-up, 80 MACE occurred. Patients with diabetes (P=0.03) or CAD (P<0.0001) had a worse long-term prognosis. However, only in patients without diabetes was CAD associated with an increased incidence of MACE (10.6% vs 45.9%, P<0.0001). In patients with diabetes, the endpoints were not different between those with and without CAD. No difference occurred in the long-term prognosis of patients with diabetes (with or without CAD) and patients without diabetes with CAD., Conclusions: We concluded that in high-risk RTC, diabetes confers a cardiovascular risk comparable to that of CAD in patients without diabetes, independent of coronary obstruction. In patients with diabetes, concomitant CAD does not add to the already very high cardiovascular risk of this population.

Patients with end-stage renal disease (ESRD) are at high risk for cardiovascular disease (CVD) and therefore should be treated according to ACC/AHA Guidelines. Scant data are available concerning the actual use of cardioprotective drugs in this population. The use of angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, aspirin, and statins was assessed in 271 (72% males, 66% Caucasians) high-risk ESRD patients on hemodialysis. The study population comprised 27% smokers, 95% with hypertension, 38% with diabetes, and 44% with dyslipidemia; 44% of patients had overt CVD at baseline, including 9% with heart failure, 9% with prior myocardial infarction, and 3% with previous myocardial revascularization. One-third of all patients were not receiving any cardioprotective drugs; among those patients who were, 42% were on one drug, 21% were on two, 3.7% were on three, and 1.5% were on four. The most prescribed agent was ACE-I (35.8%), followed by aspirin (30.6%), and beta-blockers (28.0%). The use of statins was remarkably and significantly low (4.1%) (p < 0.001), even in the higher risk subgroups (patients with diabetes or macrovascular disease). ACE-I plus aspirin was the most prescribed combination (8.5%). Cardioprotective agents recommended for risk-factor modification by the ACC/AHA Guidelines for their well-established efficacy in the general population were underutilized in this cohort of high-risk hypertensive hemodialysis patients, despite an elevated prevalence of clinically evident CVD. Speculatively, this fact may be relevant to better understand the known increased cardiovascular morbidity-mortality associated with chronic renal disease.

Background: Secondary hyperparathyroidism (SHPT) and its metabolic consequences - high serum phosphate and calcium x phosphate (Ca x P) product - are associated with cardiovascular disease in chronic kidney disease (CKD). We evaluated the relationship between PTH, mineral metabolism, vascular reactivity and arterial stiffness in patients with CKD., Methods: The study included 31 CKD patients and 12 matched controls. Brachial artery diameter was recorded at baseline and after reactive hyperemia (flow-mediated vasodilation) and 0.45 mg of trinitrate, to analyze the flow-dependent and flow-independent responses. Large vessel stiffness was evaluated on the common carotid artery., Results: Compared with controls, both flow-mediated (5.8% +/- 4.3% vs. 11.6% +/- 5.4%; p<0.001) and flow-independent (11.7% +/- 7.6% versus 23% +/- 7.5%; p<0.001) vasodilation were reduced in CKD. Flow-mediated vasodilation was negatively correlated with PTH (r=-0.416, p<0.05) and age (r=-0.365, p<0.05) and positively with flow-independent vasodilation (r=0.483, p<0.01). Blood pressure, dialysis duration, hematocrit and serum levels of Ca, P, and Ca x P product, lipids, and medications did not influence flow-mediated function. Carotid distension correlated independently and negatively with age (r=-0.681, p<0.01) and Ca x P product (r=-0.496, p<0.01) but was not influenced by PTH., Conclusion: In CKD, PTH adversely affects vascular reactivity, possibly by interfering with endothelial function, while large vessel distension is influenced by Ca x P product but not by PTH. This result suggests a dual mechanism of vascular aggression in SHPT: an endothelial effect mediated by PTH and a media/adventitial effect linked to alterations in mineral metabolism.

In the past decades new imaging techniques and developments in existing systems have been introduced. Novel ideas with strong potential in areas such as radiography, nuclear magnetic resonance, ultrasound and nuclear medicine have recently emerged or are still under development or evaluation. Positron emission tomography (PET) is finally garnering enormous interest for high-sensitivity and high-specificity molecular imaging. The combination of PET and computed tomography is proving to be very useful in clinical oncology. Functional magnetic resonance imaging and magnetic resonance spectroscopy are also emerging as strong partners in terms of functional information. Recent improvements in ultrasound imaging, such as a 3-D, tissue harmonics, high-frequency, real time, extended field of view and new contrast agents, show the potential of this methodology. Film/screen mammography represents the ultimate in radiography capacities, but new digital systems are beginning to offer even better response.

The synthesis and characterization of a new class of DOTA (1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane) monoamide-linked glycoconjugates (glucose, lactose and galactose) of different valencies (mono, di and tetra) and their Sm(III), Eu(III) and Gd(III) complexes are reported. The 1H NMR spectrum of Eu(III)-DOTALac2 shows the predominance of a single structural isomer of square antiprismatic geometry of the DOTA chelating moiety and fast rotation about the amide bond connected to the targeting glycodendrimer. The in vitro relaxivity of the Gd(III)-glycoconjugates was studied by 1H nuclear magnetic relaxation dispersion (NMRD), yielding parameters close to those reported for other DOTA monoamides. The known recognition of sugars by lectins makes these glycoconjugates good candidates for medical imaging agents (MRI and gamma scintigraphy).

The detection of sialic acid in living systems is of importance for the diagnosis of several types of malignancy. We have designed and synthesized two new lanthanide ion ligands (L1 and L2) that are capable of molecular recognition of sialic acid residues. The basic structure of these ligands consists of a DTPA-bisamide (DTPA, diethylenetriamine pentaacetic acid) whose amide moieties each bear both a boronic function for interaction with the diol groups in the side chain of sialic acid, and a functional group that is positively charged at physiologic pH values and is designed to interact with the carboxylate anion of sialic acid. The relaxometric properties of the Gd3+ complexes of these two ligands were evaluated. The relaxivity of the GdL1 complex has a significant second-sphere contribution at pH values above the pKa of its phenylboronic acid moiety. The interaction of the Gd3+ complexes of L1 and L2 with each of several saccharides was investigated by means of a competitive fluorescent assay. The results show that both complexes recognize sialic acid with good selectivity in the presence of other sugars. The adduct formed by GdL2 with sialic acid has the higher conditional formation constant (50.43+/-4.61 M(-1) at pH 7.4). The ability of such complexes to recognize sialic acid was confirmed by the results of a study on the interaction of corresponding radiolabeled complexes (153SmL1 and 153SmL2) with C6 glioma rat cells. 153SmL2 in particular is retained on the cell surface in significant amounts.

Rationale and Objectives: GdDOTP5- is a highly charged, bone-seeking paramagnetic complex that could potentially detect bone lesions by magnetic resonance imaging (MRI). To date, its pharmacokinetics, effects on organ relaxivity, and interaction with hydroxyapatite (HA) has not been described., Methods: Liver, kidney, and bone MRI images were obtained on male white rabbits after the administration of GdDOTP5- or a gold standard MRI contrast agent, GdDTPA2-. Parallel in vitro experiments quantified the effect of HA binding on GdDOTP5- -induced changes in relaxivity., Results: The 2 compounds showed similar MRI enhancements in visceral tissues, but no enhancement of bone was evident with GdDOTP5- despite confirmation of bone and HA binding of the radioactive 153SmDOTP5- and 111InDOTP5- derivatives. In vitro experiments demonstrated that GdDOTP5--induced changes in relaxivity were silenced upon HA binding but could be recovered by acid elution of the complex., Conclusions: HA binding assays revealed that GdDOTP5- is essentially MR silent when bound to bone, likely because of the exclusion of all outer sphere water molecules from the surface of the complex. These data suggest a novel strategy for creating highly sensitive, switchable MRI contrast agents.

Guidelines for the detection of coronary artery disease (CAD) and assess of risk in renal transplant candidates are based on the results of noninvasive testing, according to data originated in the nonuremic population. We evaluated prospectively the accuracy of 2 noninvasive tests and risk stratification in detecting CAD (>or=70% obstruction) and assessing cardiac risk by using coronary angiography (CA). One hundred twenty-six renal transplant candidates who were classified as at moderate (>or=50 years) or high (diabetes, extracardiac atherosclerosis, or clinical coronary artery disease) coronary risk underwent myocardial scintigraphy (SPECT), dobutamine stress echocardiography, and CA and were followed for 6 to 48 months. The prevalence of CAD was 42%. The sensitivities and negative predictive values for the 2 noninvasive tests and risk stratification were <75%. After 6 to 48 months, there were 18 cardiac events, 9 fatal. Risk stratification (P=0.007) and CA (P=0.0002) predicted the crude probability of surviving free of cardiac events. The probability of event-free survival at 6, 12, 24, 36, and 48 months were 98%, 98%, 94%, 94%, and 94% in patients with <70% stenosis on CA and 97%, 87%, 61%, 56%, and 54% in patients with >or=70% stenosis. Multivariate analysis showed that the sole predictor of cardiac events was critical coronary lesions (P=0.003). Coronary angiography may still be necessary for detecting CAD and determining cardiac risk in renal transplant candidates. The data suggest that current algorithms based on noninvasive testing in this population should be revised.

Unlabelled: Lymphatic drainage plays an important role in the uptake of particulates in the respiratory system, being also associated to the spreading of lung cancer through metastasis development. In recent years solid lipid nanoparticles (SLN) have been proposed as carriers of anti-tumoural drugs, for their low toxicity and surface characteristics make them suitable for either imaging (gamma-scintigraphy) or therapy upon encapsulation of cytotoxic drugs. Assessment of inhaled radiolabelled SLN biodistribution is described in the present work., Methods: Nanoparticles (200 nm) were radiolabelled with 99mTc using the lipophilic chelator D,L-hexamehylpropyleneamine oxime (HMPAO). Biodistribution studies were carried out following aerosolisation and administration of a 99mTc-HMPAO-SLN suspension to a group of adult male Wistar rats. A 60 min dynamic image acquisition was performed in a gamma-camera, followed by static image collection at 30 min intervals up to 4 h postinhalation. Radiation counting was performed in organ samples, collected after the animals were sacrificed., Results: The data show an important and significant uptake of the radiolabelled SLN into the lymphatics after inhalation, and a high rate of distribution in periaortic, axillar and inguinal lymph nodes., Conclusion: Results indicate that SLN could be effective colloidal carriers for lymphoscintigraphy or therapy upon pulmonary delivery.

Two DTPA derivatives, a mono-amide derivative containing an iodinated synthon, DTPA-IOPsp (L(1)) and the ligand DTPA(BOM)(3) (BOM=benzyloxymethyl) (L(2)), radiolabelled with (153)Sm(3+) and (111)In(3+), were studied as potential hepatospecific gamma scintigraphic agents. In vivo studies with Wistar rats show that the main excretory pathway for all the chelates studied is the hepatobiliary system. The complexes of L(2) show even greater hepatobiliary specificity than L(1), perhaps as a consequence of longer blood circulation times due to their strong affinity towards HSA. The (153)Sm(3+) chelates are also more hepatospecific than the corresponding (111)In(3+) chelates. The La(3+) and In(3+) chelates of L(1) and L(2) show some structural and dynamic differences in aqueous solution, as studied by (1)H NMR spectroscopy. While only two nona-coordinated isomers were observed for the La(3+) complexes with both ligands, its number is much larger in the In(3+) complexes, with both octa- and hepta-coordinated species (with unbound side arms), as well as structural isomers for each coordination number.

Background: The aim of this study was to examine prospectively the impact of renal transplantation on the morphological and functional characteristics of the carotid arteries and heart in a group of end-stage renal failure patients without overt cardiovascular disease, followed up for >3 years., Methods: Twenty-two patients were evaluated 2-3 weeks after renal transplantation, and again 12 and 40 months post-transplant, using high resolution ultrasound imaging and echocardiography., Results: Kidney and patient survival were 100% at the end of follow-up without any major cardiovascular events. After 40+/-1.2 months, carotid morphological parameters were normalized: carotid intima-media thickness fell from 788+/-24 to 676+/-32 microm (P<0.01) and the carotid wall/lumen ratio fell from 118+/-3 to 103+/-3 microm (P<0.01). Significant reduction of left ventricular (LV) posterior wall thickness (11.5+/-0.2 to 11.3+/-0.2 mm, P<0.05) and LV mass index (172+/-9 to 158+/-8 g/m(2), P<0.01) was already observed after 12+/-0.2 months. Further reduction of LV posterior wall thickness (10.4+/-0.3 mm, P<0.01) and of LV mass index (136+/-7 g/m(2), P<0.01) also occurred after 40+/-1.2 months. However, carotid distensibility (19.5+/-2.1 vs 22+/-2.4, not significant (NS)) and LV compliance (early to atrial flow ratio: 1.2+/-0.1 vs 1.3+/-0.1, NS) remained abnormal, and normalization of the LV mass was attained by only 25% of the patients with LV hypertrophy on baseline. Multiple stepwise regression analysis showed that the rate of change of reduction of the intima-media thickness was influenced by age (negative association, P<0.001) and was positively related to white race (P<0.05), female sex (P<0.01) and to the parallel reduction of maximum carotid diameter (P<0.001). Reduction of LV mass index over time was negatively related to the duration of dialysis treatment and to the parallel increase observed in body mass index and haematocrit, and was positively related to the simultaneous reduction of diastolic blood pressure (P<0.01 for all variables)., Conclusions: Successful renal transplantation improves but does not cause complete regression of the cardiovascular alterations of end-stage renal disease. Only intima-media thickness was normalized by transplantation, whereas LVMI and carotid and ventricular distensibility remained abnormal. The results suggest that extended duration of dialysis, weight gain, high blood pressure and high haematocrit may adversely affect the rate of change of post-transplant cardiovascular hypertrophy.

Background: Left ventricular hypertrophy is common in renal transplant patients but the factors influencing its development remain to be determined. The present investigation was conducted to study the effect of blood pressure load on the left ventricular mass of recently transplanted patients using 24-h ambulatory blood pressure monitoring (ABPM)., Methods: We studied 30 renal transplant (RT) patients (36.1+/-13.7 years old, 11 males, 26 Whites, 4 diabetics, 15 under antihypertensive medication, 21 recipients of cadaver donors, and all treated with steroids, cyclosporin and azathioprine and with adequate (serum creatinine < 1.8 mg/100 ml) renal function). The median duration of dialysis treatment before transplant was 37 months, and the studies were performed during the first 40 days post-transplantation. Blood pressure was measured after a 15-min rest (casual blood pressure) and during a 24-h period with a SpaceLabs apparatus. Echocardiograms were obtained from all patients., Results: Mean left ventricular mass index (LVMI) was 153+/-44 g/m2; casual systolic and diastolic BP (mmHg) was 152+/-25 and 92+/-13, whereas systolic and diastolic 24-h BP was 133+/-12 and 85+/-8, respectively. The systolic sleeping BP/awake systolic BP (SSBP/ASBP) ratio was 0.94+/-0.07, and 73% of the patients did not show a significant (>10%) fall of systolic blood pressure during sleep. Multivariate analysis showed that awake systolic blood pressure was the only variable that independently influenced LVMI after adjusting for confounding factors (regression coefficient = 0.49, p = 0.01). Casual systolic and diastolic BP, sleeping systolic and diastolic blood pressure, 24-h heart rate, age, race, gender, smoking, body mass index, duration of dialysis, diabetes, antihypertensive and immunosuppressive drugs and levels of hematocrit, creatinine and serum lipids did not correlate with LVMI., Conclusion: The data indicate that left ventricular hypertrophy during the early post-transplant period is mainly influenced by awake blood pressure load. They also suggest that ABPM may be more useful in the diagnosis and management of post-transplant hypertension than casual BP. The findings emphasize the importance of rigid blood pressure control in renal transplant recipients.

Studying the kinetics of blood flow in the pulmonary artery using non-invasive techniques may be an important tool in assessing the prognosis of lung diseases. The aim of this study was to ascertain dynamic parameters of pulmonary blood flow, particularly the velocity of a small bolus of a radioactive tracer after intravenous injection. Since the shape and distribution pattern of the bolus changes substantially from frame to frame, common image processing techniques for motion detection or other techniques, such as accumulation of subtracted images, segmentation and spectral analysis with temporal/spatial filtering, are unable to properly evaluate the motion of the bolus. However, the passage of the bolus from the arm to the lungs was visualized with good contrast through acquisition of a first pass sequence of scintigraphic images. The wave form of the bolus becomes increasingly complex as it progresses towards the pulmonary artery. In the proposed method the time-activity curves for each pixel are displayed. It is assumed that the peaks of the maximum counts in these curves correlate with the time after injection that the bolus takes to cross each pixel (bolus head). The bolus head contains information on time, space and activity, and allows the velocity of the studied fluid to be calculated. We demonstrated a mean velocity through the pulmonary artery trunk in resting patients of approximately 11 cm/s, with a mean residence time of 0.5 s.

Background: Age, diabetes and concomitant cardiovascular disease, recorded at the initiation of dialysis, allows the identification of patients with a high probability of early mortality. When all of these factors are taken into account the mortality rate of dialysis patients is still 3.5 times higher than for the general population. Information on the factors that increase the mortality of patients lacking the major cardiovascular risk factors is important because these are likely to be correctable, especially if detected early., Methods: We investigated prospectively the relevance of blood pressure and other variables recorded at the initiation of dialysis treatment on the survival of a group of 103 relatively young adult haemodialysis patients (mean age 44.3 years +/-13 SD), with a low prevalence of comorbidity and a median follow-up period of 79 months. Data were analysed by the Cox proportional regression model and survival curves were constructed by the Kaplan-Meier method., Results: Forty-four patients died, 20 (46%) of whom as a result of cardiovascular causes. Multivariate analysis showed that mortality was associated with age (P=0.0001), serum creatinine (P=0.005, negative association), left ventricular (LV) mass (P=0.003) and hypertension (P=0.03). Mortality was increased by 7% for each additional year of age, by 0.7% for each 1 g increase in LV mass, and was reduced by 23% for each additional mg/dl of serum creatinine. Hypertensive patients had a higher probability (x2.2) of dying compared with normotensive patients., Conclusions: In addition to age and conditions of occult malnutrition, hypertension and LV hypertrophy, when present at the initiation of dialysis, play a major role in the mortality of low risk, relatively young dialysis patients. These potentially correctable factors should be actively sought and treated during the early stage of renal insufficiency to improve prognosis.

A large series of structurally related diethylenetriaminepentaacetic acid amide derivatives with different structures and lipophilic properties were synthesized and radiolabeled with (111)In(3+). Two of the more hydrophobic compounds studied ([(111)In]L(9) and [(111)In]L(10)) showed high affinity for human serum albumin (HSA). The biodistribution and clearance properties shown by all complexes upon injection in Wistar rats were followed by gamma imaging. The blood retention time of the chelates correlates better with their binding to HSA than with their hydrophilic/lipophilic ratio. Hydrophilic and negatively charged complexes undergo renal retention, while the majority of the lipophilic complexes are retained in the blood for a longer period of time and are cleared through the liver.

Studies in various animal species have recently shown that (99m)Tc-BIG has practical and dosimetric benefits for renal imaging that could probably make it a good alternative to (99m)Tc-2, 3-dimercaptosuccinic acid ((99m)Tc-DMSA). In this study, using the baboon experimental model, the biodistribution of (99m)Tc-BIG and (99m)Tc-DMSA are compared. It is demonstrated that early good contrast imaging and more favourable dosimetry is possible with (99m)Tc-BIG compared to (99m)Tc-DMSA, confirming the quoted previous findings with small animals. Time-activity curves for kidneys and other organs support these findings, and MIRDOSE software provided the dosimetry.