Nephrology and renal replacement therapy in Romania--transition still continues (Cinderella story revisited).

INTRODUCTION. This report describes the current status of nephrology and renal replacement therapy (RRT) in Romania, a country with previously limited facilities, highlighting national changes in the European context. METHODS: Trends in RRT development were analysed in 2003, on a national basis, using the same questionnaires as in previous surveys (1991, 1995). Survival data and prognostic risk factors were calculated retrospectively from a large representative sample of 2284 patients starting RRT between January 1, 1995 and December 31, 2001 (44% of the total RRT population investigated). RESULTS: In 2003, RRT incidence [128 per million population (p.m.p.)] and prevalence (250 p.m.p.) were six and five times higher, respectively, than in 1995. The annual rate of increase in the stock of RRT patients (11%) was supported mainly by an exponential development of the continuous ambulatory peritoneal dialysis (CAPD) population (+600%), while the haemodialysis (HD) growth rate was stable (+33%) and renal transplantation made a marginal contribution. Renal care infrastructure followed the same trend: nephrology departments (+100%) and nephrologists (+205%). The characteristics of RRT incident patients changed accordingly to current European epidemiology (increasing age and prevalence of diabetes and nephroangiosclerosis). The estimated overall survival of RRT patients in Romania was 90.6% at 1 year [confidence interval (CI) 89.4-91.8] and 62.2% at 5 years (CI 59.4-65.0). Patients' survival was negatively influenced (Cox regression analysis) by age >65 years (P < 0.001), lack of pre-dialysis monitoring by a nephrologist [P = 0.01, hazards ratio (HR) = 0.8], severe anaemia, lack of erythropoetin treatment (P < 0.001, HR = 0.6), and co-morbidity, e.g. cardiovascular diseases (P < 0.001, HR = 1.8) and diabetes mellitus (P < 0.001, HR = 2.2). CONCLUSIONS: Although the rate of increase in RRT patient stock in 1996-2003 in Romania was the highest in Europe, the prevalence remained below the European mean. As CAPD had the greatest expansion, followed by HD, an effective transplantation programme must be set up to overcome the imbalance. The quality of RRT appears to be good and survival was similar to that in other registries. Further evolution implies strategies of prevention, based on national surveys, supported by the Romanian Renal Registry.     

The use of 3D surface fitting for robust polyp detection and classification in CT colonography

In this paper we describe the development of a computationally efficient computer-aided detection (CAD) algorithm based on the evaluation of the surface morphology that is employed for the detection of colonic polyps in computed tomography (CT) colonography. Initial polyp candidate voxels were detected using the surface normal intersection values. These candidate voxels were clustered using the normal direction, convexity test, region growing and Gaussian distribution. The local colonic surface was classified as polyp or fold using a feature normalized nearest neighborhood classifier. The main merit of this paper is the methodology applied to select the robust features derived from the colon surface that have a high discriminative power for polyp/fold classification. The devised polyp detection scheme entails a low computational overhead (typically takes 2.20 min per dataset) and shows 100% sensitivity for phantom polyps greater than 5 mm. It also shows 100% sensitivity for real polyps larger than 10 mm and 91.67% sensitivity for polyps between 5 to 10 mm with an average of 4.5 false positives per dataset. The experimental data indicates that the proposed CAD polyp detection scheme outperforms other techniques that identify the polyps using features that sample the colon surface curvature especially when applied to low-dose datasets.     

Androgen receptor independent cardiovascular action of the antiandrogen flutamide

We have previously shown that flutamide (specific antagonist of the androgen receptor) has antihypertensive effects. In the present study we examined the mechanisms of flutamide action in the vasculature. The vascular effects of flutamide were assayed in aortae isolated from male or female Sprague-Dawley rats and from rats or mice lacking a functional androgen receptor ( tfm, testicular feminization mutation). The effect of flutamide on coronary flow was tested in isolated hearts. In addition, male hypertensive rats with tfm mutation were treated with flutamide, and blood pressure was monitored. Flutamide induced a relaxation of rat aortae from all the strains used (maximum relaxation at 10 microM: 51.3+/-5.2% of phenylephrine contraction) and increased the coronary flow. The aortic relaxation to flutamide was abolished by endothelium removal, or by inhibition of nitric oxide synthase, guanylyl cyclase, and tyrosine kinase but not by calmodulin inhibition. Flutamide treatment attenuated the development of hypertension in mouse renin transgenic rats with the tfm mutation. Flutamide produces direct vasodilation by inducing release of NO from the endothelium and causes subsequent activation of soluble guanylyl cyclase in an active androgen receptor independent manner. This response may contribute to the observed antihypertensive actions of flutamide.     

Heart failure due to ischemia--the adaptive mechanisms

Chronic myocardial ischemia is the leading cause of disturbances in myocardial contractility (myocardial infarction) or hemodynamic overload upon the left ventricle. The heart reactions consist in a series of adaptative mechanisms in order to maintain its pump function: Frank-Starling mechanism, myocardial hypertrophy and neurohumoral activation. In heart failure, the cardiac output is maintained by an increase of the preload which enhances the contractility (Frank-Starling law). Myocardial ischemia influences the systolic and diastolic function. The decrease of cardiac output leads to neurohumoral responses which, in the initial stages of cardiac failure are compensatory; along with the progression of the disease, they exert adverse effects. Increased activity of the sympathetic nervous system induces high cardiac rates, chronotropic incompetence. Activation of the renin-angiotensin system held to myocardial and vascular hypertrophy, vasoconstriction, fluid retention. Endothelin is the most powerful vasoconstrictor; its plasmatic concentrations correlate with the severity of the disease. Vasodilator mediators released in cardiac failure are the natriuretic peptide, nitric oxide, dopamine, prostacicline, bradikinin.     

Is the age a limiting factor of functional capacity and cardiac performance in patients with chronic myocardial infarction ?

Actually the old age is not considered a contra-indication of cardiac rehabilitation, although it influences the prognosis of patients with chronic myocardial infarction. The objective of the paper is the study of age as a limiting factor of the cardiac performance and exercise capacity at patients with myocardial infarction at the admission in rehabilitation programmes. METHODS: Among the patients admitted in the Department of Internal Medicine of Rehabilitation Hospital of Iasi there were selected 132 with chronic myocardial infarction; they were divided into two groups: group A of 56 patients more than 55 years old and group B of 76 under 55. There were analysed the clinical features (risk factors, symptoms), the cardiac performance (by echographic study of the regional and global abnormalities of myocardial contractility) and the functional capacity (by exercise testing at the ergometric bicycle). RESULTS: Both groups were similar by the point of view of the prevalence of the risk factors and location of the infarction. The ejection fraction, although smaller at the group A (45% vs 50%), did not reach the statistical significance. The exercise testing revealed a lower capacity of the group A, marked by higher levels of the cardiac rate and time-tension index at similar levels of exercise. The metabolic equivalent (MET) and VO2max were significantly lower (p = 0.001 respectively 0.002). There can be concluded that the age diminishes the exercise capacity of the patients with myocardial infarction without a marked influence of the cardiac performance. The last one depends on the infarction size and the myocardial status while the lowering of the functional capacity is influenced by noncardiac factors as well.     

A role for serum cytokines and cell adhesion molecules in the non-invasive diagnosis of colorectal cancer

Colorectal cancer (CRC) remains a major cause of cancer-related mortality. Consequently, new diagnostic and therapeutic approaches are being investigated including the serum levels of cytokines and other molecules, although the results are often inconclusive. Thus, the present study aimed to determine whether serum level of cytokines, cell adhesion molecules or matrix metalloproteinases (MMPs), alone or in combination, may contribute to the non-invasive diagnosis of CRC. The serum levels of nine cytokines [ILs; IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IL-22 and IL-33, and interferon (IFN)-γ], two cell adhesion molecules (intercellular adhesion molecule-1 and P-selectin) and an MMP-7 were measured by ELISA in 33 patients with CRC and 35 healthy controls. Combined capacity of all molecules to detect the presence of CRC was assessed by logistic regression. Molecules and molecule combinations were tested for all stages and tumor grades. A significant increase was identified for IL-8 in patients compared with healthy controls; IL-10 was found to be significantly decreased. The biomarker potential of each significantly modified molecule was tested: IL-8 had a sensitivity of 0.865, a specificity of 0.600 and an area under the curve (AUC) of 0.777; for IL-10, sensitivity was 0.65, specificity was 0.69, with an AUC of 0.689. Logistic regression determined the best discriminative potential between patients and control groups for the combination IL-4 + IL-6 + IL-8 + IFN-γ, with 0.97 sensitivity and 0.58 specificity. For the early stages of CRC, the combination IL-6 + IL-8 + IL-22 showed good performance. It was concluded that increased IL-8 had potential as single biomarker in CRC. Cytokine combinations are superior to single cytokine analysis in showing the presence of CRC.     

The challenges of androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling.     

Aluminide Diffusion Coatings on IN 718 by Pack Cementation

This paper addressed the issues of both direct and indirect synthesis of Ni aluminides by pack cementation (pure Ni and IN 718 superalloy). On the Al-Ni diffusion twosome under pressure, at temperatures below and above the Al melting temperature, the appearance and evolution of diffusion porosity because of the Kirkendall–Frenkel effect manifestation was highlighted. It has been confirmed that, as the temperature rises above the Al melting temperature, the porosity decreases. Nickel-based superalloys, and in particular IN 718, significantly increase their performance by increasing the aluminides proportion in the top diffusion coating. This is made possible by changing the value of the Al and Ni weight percentage ratio in this area (noted as Al/Ni). In the case of the diffusion twosome between IN 718 and pack aluminizing mixtures, having in their composition as active components Al powder, Ferroaluminum (FeAl40) or mixtures of Al and Fe powders, at processing temperatures above the Al melting temperature, by modifying the active component of the mixture, substantial changes in the Al/Ni values were observed, as well as in the maximum %Al in the diffusion coating and of its thickness. It was found that, when switching from Al to FeAl40 or powder mixture (Al + Fe), the Al/Ni value changes between 3.43 and 1.01, from initial subunit values. The experiments confirmed that the highest %Al in the top aluminized diffusion coating, for IN 718, was obtained if the powder mixture contained 66.34 wt.% Al.     

Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin

The development of new orally dispersible tablets containing amlodipine (AML) inclusion complexes in hydroxypropyl-β-cyclodextrin (HP-β-CD) and in methyl-β-cyclodextrin (Me-β-CD) was studied. The methods of obtaining amlodipine and the physical and chemical properties of the inclusion complexes using the two cyclodextrins was investigated separately. Solid inclusion complexes were obtained by three methods: kneading, coprecipitation, and lyophilization, at a molar ratio of 1:1. For comparison, a physical mixture in the same molar ratio was prepared. The aim of the complexation process was to improve the drug solubility. As the lyophilization method leads to a complete inclusion of the drug in the guest molecule cavity, for both used cyclodextrins, these types of compounds were selected as active ingredients for the design of orally dispersible tablets. Subsequently, the formulation of the orodispersible tablets containing AML-HP-β-CD and AML-Me-β-CD inclusion complexes and quality parameters of the final formulation were evaluated. The results prove that F1 and F4 formulations, based on silicified microcrystalline cellulose, which contains insignificant proportions of very small or very large particles, had the lowest moisture degree (3.52% for F1 and 4.03% for F4). All of these demonstrate their porous structure, which led to good flowability and compressibility performances. F1 and F4 formulations were found to be better to manufacture orally dispersible tablets.     

Aluminum Perlite Syntactic Foams

This paper presents the usage of spark plasma sintering (SPS) as a method to obtain aluminum-expanded perlite syntactic foams with high porosity. In the test samples, fine aluminum powder with flaky shape particles was used as matrix material and natural, inorganic, granular, expanded perlite was used as a space holder to ensure high porosity (35–57%) and uniform structure. SPS was used to consolidate the specimens. The structures were characterized by scanning electron microscopy and compression tests. Energy absorption (W~7.49 MJ/m³) and energy absorption efficiency (EW < 90%) were also determined.