Variability of Chalcone Synthase in Chamomile Accessions (Matricaria chamomilla).

Chamomile (Matricaria chamomilla) is an important medicinal plant whose beneficial activities partly rely on certain flavonoids. The first dedicated step in flavonoid biosynthesis is chalcone synthase (CHS, EC 2.3.1.74). The genomic DNA of CHS was studied in six chamomile specimens from different genotypes to describe interspecimen, as well as interspecific, variability. One specimen of M. discoidea was included as an outgroup. The two exons of CHS of M. chamomilla (McCHS) and M. discoidea (MdCHS) were 188 bp and 1,011 bp long, separated by an intron of variable length between 192 and 199 bp in McCHS and 201 bp in MdCHS, respectively. The two exons with 5.3 and 6.2 mutations per 100 bp, respectively, were more conserved than the intron with 11.5 mutations per 100 bp. In total, 96 SNPs were detected in both species, of which 12 SNPs were only present in MdCHS and 80 SNPs only in McCHS. Overall, 70 haplotypes (multilocus genotypes, MLGs) were detected. The samples could be classified into two groups, a 'compact' group of a low number and diversity of haplotypes and a 'variable' group of a high number and diversity of haplotypes. Of the 74 SNPs in McCHS, only six SNPs were non-synonymous. However, the amino acid changes did not affect critical areas of the enzyme. The combination of the six SNPs resulted in nine translated amino acid MLGs. The CHS network located MdCHS, due to the crossing barrier, quite distant from chamomile. MdCHS docked to McCHS at a position from where McCHS divergently evolved into two directions.

The Importance of Natural and Acquired Immunity to SARS-CoV-2 Infection in Patients on Peritoneal Dialysis.

The pandemic caused by the SARS-CoV-2 virus had a great impact on the population of patients treated with peritoneal dialysis (PD). This study demonstrates the impact of infection and vaccination in 66 patients treated with PD and their outcomes during a 6-month follow-up. This is the first research that has studied the dynamics of anti-SARS-CoV-2 IgG in serum and effluent. In our research, 57.6% of PD patients were vaccinated, predominantly with Sinopharm (81.6%), which was also the most frequently administered vaccine in the Republic of Serbia at the beginning of immunization. During the monitoring period, the level of anti-SARS-CoV-2 IgG antibodies in the PD patients had an increasing trend in serum. In the group of vaccinated patients with PD, anti-SARS-CoV-2 IgG antibodies had an increasing trend in both serum and effluent, in contrast to non-vaccinated patients, where they decreased in effluent regardless of the trend of increase in serum, but statistical significance was not reached. In contrast to vaccinated (immunized) patients who did not acquire infection, the patients who only underwent the COVID-19 infection, but were not immunized, were more prone to reinfection upon the outbreak of a new viral strain, yet without severe clinical presentation and with no need for hospital treatment.

Multi-Swarm Algorithm for Extreme Learning Machine Optimization.

There are many machine learning approaches available and commonly used today, however, the extreme learning machine is appraised as one of the fastest and, additionally, relatively efficient models. Its main benefit is that it is very fast, which makes it suitable for integration within products that require models taking rapid decisions. Nevertheless, despite their large potential, they have not yet been exploited enough, according to the recent literature. Extreme learning machines still face several challenges that need to be addressed. The most significant downside is that the performance of the model heavily depends on the allocated weights and biases within the hidden layer. Finding its appropriate values for practical tasks represents an NP-hard continuous optimization challenge. Research proposed in this study focuses on determining optimal or near optimal weights and biases in the hidden layer for specific tasks. To address this task, a multi-swarm hybrid optimization approach has been proposed, based on three swarm intelligence meta-heuristics, namely the artificial bee colony, the firefly algorithm and the sine-cosine algorithm. The proposed method has been thoroughly validated on seven well-known classification benchmark datasets, and obtained results are compared to other already existing similar cutting-edge approaches from the recent literature. The simulation results point out that the suggested multi-swarm technique is capable to obtain better generalization performance than the rest of the approaches included in the comparative analysis in terms of accuracy, precision, recall, and f1-score indicators. Moreover, to prove that combining two algorithms is not as effective as joining three approaches, additional hybrids generated by pairing, each, two methods employed in the proposed multi-swarm approach, were also implemented and validated against four challenging datasets. The findings from these experiments also prove superior performance of the proposed multi-swarm algorithm. Sample code from devised ELM tuning framework is available on the GitHub.

Intraspecific Genetic Diversity of Cistus creticus L. and Evolutionary Relationships to Cistus albidus L. (Cistaceae): Meeting of the Generations?

Cistus (Cistaceae) comprises a number of white- and purple-flowering shrub species widely distributed in the Mediterranean basin. Within genus Cistus, many taxa are subject to various taxonomic uncertainties. Cistus creticus, a prominent member of the purple-flowered clade, is a prime case of the current taxonomic troubles. Floras and databases approve different species names and utilise different or additional/fewer synonyms. Various intraspecific classification systems based on subspecies or varieties are in use. The inconsistent determination of plant material makes it difficult to compare literature regarding the phytochemical diversity and biological activities of plant material and impedes a systematic utilization of the manifold medicinal properties of C. creticus. In the present investigation, we used DNA sequence data from one nuclear region (ITS) and two chloroplast regions (trnL-trnF, rpl32-trnL) to test the intraspecific genetic diversity of C. creticus and its evolutionary relationships to the closely related C. albidus. The combined DNA data confirmed C. creticus as a rather heterogeneous species that integrates two major evolutionary lineages with clearly different genetic characteristics. The 'Eastern Mediterranean clade' seems to represent old and ancestral characteristics. This lineage exhibits a close relationship to the geographically distant C. albidus, expressed by very closely related ribotypes and an interspecifically shared chlorotype. The 'Western Mediterranean clade' is characterized by a distinctive ITS polymorphism (co-occurring paralogous ribotypes) and more distantly related chlorotypes. The formation of the genetically complex 'Western Mediterranean clade' seems to have involved hybridization and recurrent formation or migration movements.

Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy provides novel insights into the staphylococcal glycocode.

Surface carbohydrate moieties are essential for bacterial communication, phage-bacteria and host-pathogen interaction. Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or ß-O-linked N-acetyl-glucosamine (α-/ß-O-GlcNAc) residues. GlcNAc modifications have attracted particular interest, as they were shown to govern staphylococcal adhesion to host cells, to promote phage susceptibility conferring beta-lactam resistance and are an important target for antimicrobial agents and vaccines. However, there is a lack of rapid, reliable, and convenient methods to detect and quantify these sugar residues. Whole cell Fourier transform infrared (FTIR) spectroscopy could meet these demands and was employed to analyse WTAs and WTA glycosylation in S. aureus. Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules. We could demonstrate that α- or ß-O-GlcNAc WTA substituents can be clearly differentiated by chemometrically assisted FTIR spectroscopy. Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.

Predictive value of echocardiography and its relation to Kt/V and anthropometric parameters in hemodialysis patients.

BACKGROUND: In order to evaluate the predictive value of echocardiograph parameters for mortality of hemodialysis patients and their relation to Kt/V and anthropometry, a prospective, single center study was analyzed post-hoc. METHODS: This analysis encompassed 106 patients on maintenance hemodialysis monitored for 108 months from 1996 to 2004. spKt/V was calculated using the Daugirdas formula. Anthropometric measurements included mid-arm muscle measurements (MAMC) and percentage of body fat (%fat). Echocardiography included the estimations of left ventricular wall thickness, dimensions and volumes (EDV, ESV), systolic LV function (ejection fraction - EFLV, fractional shortening - VCF, stroke volume - SV) and diastolic LV function (E/A, VTI-A wave of transmitral flow velocity), left atrial diameter, as well as assessment of clinical and biochemical parameters. The Cox proportional hazard model was used to estimate predictive values of echocardiograph parameters. RESULTS: Kt/V correlated significantly with left ventricular systolic and diastolic volumes and function, septal and posterior wall thickness and left atrium dimension. MAMC and %fat also correlated with many echocardiograph parameters. Multivariate Cox regression selected age [HR 1.07; CI (1.03-1.12); p < 0.01], albumin [HR 0.88; CI (0.79-0.97); p < 0.05] and left atrium dimension - binary [values > 4 cm were marked as "1" and others "0" - HR 3.76; CI (1.56-9.03); p < 0.01] as independent predictors of death. CONCLUSION: Left atrium dimension was the most important predictor of mortality among the echocardiograph parameters. Many of these parameters were related to Kt/V and anthropometric measurements and could be the combined consequence of hypervolemia and hypertension.

Inflammatory markers as mortality predictors in continuous ambulatory peritoneal dialysis patients.

BACKGROUND/AIM: Besides peritonitis, the most common complication, indicators of chronic inflammation are also present in patients treated by peritoneal dialysis. The aim of this study was to analyze the predictive value of inflammatory parameters on mortality of continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Eighty-seven patients (57 males), aged from 30 to 85 [62.92 (10.61)] years who had been treated by a chronic program of CAPD for 3-113 months were analyzed. The basal period lasted 3 months with a follow-up of 30 months. Clinical parameters, dialysis adequacy and laboratory parameters including some inflammatory markers: serum amyloid-A (SAA), high sensitive C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR) and leukocytes were determined for each patient. Cox regression analysis selected the parameters of univariate and multivariate survival analysis. RESULTS: During the follow-up period, 37 patients (42.5%) died. Univariate analysis selected the following potential mortality predictors (p<0.10): age, months on CAPD, residual urine output, presence of cerebrovascular insult (CVI), KT/V, serum urea and albumin concentrations, SAA, hs-CRP, fibrinogen and ESR. In the multivariate survival analysis four models were created, each with a single inflammatory parameter. In all of these models, besides the age and CVI, inflammatory parameters were the most significant mortality predictors. When the inflammatory markers were analyzed altogether, multivariate analysis established that independent mortality predictors in this group of patients were: SAA, age and CVI. CONCLUSION: It may be concluded that in this studied group treated by CAPD, SAA was the most significant independent mortality predictor among the analyzed inflammatory markers.

Depression and quality of sleep in maintenance hemodialysis patients.

INTRODUCTION: Sleep disorders and psychological disturbances are common in end-stage renal disease (ESRD) patients. However, despite their frequency and importance, such conditions often go unnoticed, since all patients do not clearly manifest fully expressed symptoms. OBJECTIVE: This study aimed to determine the prevalence of depression and poor sleep quality and to examine the association between these disorders and demographic, clinical and treatment-related characteristics of ESRD patients on hemodialysis (HD). METHODS: The study included 222 patients (132 men and 90 women), mean age 57.3 +/- 11.9 years, from 3 HD centers in Central Serbia, which provided us with biochemical parameters and demographic data. Sleep quality and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI), respectively. RESULTS: The average BDI was 16.1 +/- 11.3. Depressed patients were significantly older (p=0.041), had a significantly lower dialysis adequacy (p=0.027) and a significantly worse quality of sleep (p < 0.001), while they did not show significant difference as regarding sex, employment, marital status, comorbidities, dialysis type, dialysis vintage, shift and laboratory parameters.The average PSQI was 7.8 +/- 4.5 and 64.2% of patients were poor sleepers. Poor sleepers were significantly older (p = 0.002), they were more often females (p = 0.027) and had a significantly higher BDI (p < 0.001), while other investigated variables were. not correlated with sleep quality. A statistically significant positive correlation was found between BDI and PSQI (r = 0.604; p < 0.001). CONCLUSION: Depression and poor sleep quality are frequent and interrelated among HD patients.

A comparison of markers of myocardial injury and their relation to nutritional parameters in hemodialysis patients.

BACKGROUND: Serum cardiac troponin T (cTnT) is a valuable marker of ischemic heart disease (IHD) and left ventricular hypertrophy, as well as a mortality predictor in hemodialysis populations. We compared the value of cTnT, creatinine kinase (CK)-MB mass and myoglobin as mortality predictors in our hemodialysis patients and evaluated their relation to nutritional status. METHODS: A total of 118 hemodialysis patients were prospectively studied from January 2004 to April 2013. Clinical and laboratory evaluations during the 12-month baseline period included the history of IHD, signs of left ventricular hypertrophy (LVH), Kt/V and serum cardiac markers together with the percentage of body fat (%fat), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), triceps skinfold (TSF) and BMI. RESULTS: Underweight patients had significantly higher cTnT values (Mann-Whitney, p<0.05). Correlation analysis (Spearman) showed an inverse association between cTnT and TSF (ρ=-0.22, p<0.05), as well as between CK-MB mass and TSF (ρ=-0.26, p<0.01). In men cTnT also correlated inversely with %fat (ρ=-0.27, p<0.05) and BMI (ρ=-0.33, p<0.05). In addition, myoglobin was correlated significantly with MAC, MAMC and albumin. Among cardiac markers cTnT was the only independent variable predicting mortality (Multivariate Cox regression, HR=1.04 CI (1.01-1.07); p<0.01; measurement units 0.01 µg/L). CONCLUSION: Troponin T and CK-MB mass were significantly elevated in the underweight patient group. Troponin T was the only independent cardiac marker predictor of all cause mortality in our hemodialysis patients.

Correlation of kidney size with kidney function and anthropometric parameters in healthy subjects and patients with chronic kidney diseases.

BACKGROUND/AIM: Echosonography is a simple, noninvasive method of kidney visualization. The objective of this study was to compare the kidney echosonograpic characteristics with the kidney function and anthropometric characteristics in healthy subjects and patients with the chronic kidney disease (CKD). METHODS: The study involved 49 patients (21 men; 46.02 ± 14.27 years) with CKD and the control group of 46 healthy persons (20 males; 45.45 ± 18.48 years). Physical examination, kidney echosonography and laboratory analyses including creatinine clearance (Ccr; 24 h and calculated by Cockroft--Gault (C--G) formula) were done in all persons. RESULTS: There was no significant difference in age and sex between two groups but serum creatinine concentration was significantly higher (218.8 vs. 84.5 µmol/L) and Ccr significantly lower (66.44 vs. 94.20 mL/min, C--G) in patient group. The left kidney was larger in both groups, but the only significant difference was in kidney depth (p < 0.01). There was significant correlation between all measured kidney dimensions, volume, parenchymal thickness and serum creatinine concentration and Ccr (C--G) in patient group. In the controls, there was no significant correlation between the kidney size and function, but there was a significant correlation between the kidney width, depth, volume and patients' age and anthropometric parameters. On the contrary, all analyzed parameters of kidney size, except volume, did not correlate significantly with the anthropometric parameters of patients. CONCLUSION: Kidney size of patients with CKD correlated significantly with kidney function, while correlation with anthropometric parameters, which is otherwise present in healthy subjects, was lost in patients with CKD.

Correlation of bone alkaline phosphatase and iPTH with some basic biochemical markers in predialysis and dialysis patients.

BACKGROUND: Bone alkaline phosphatase (BALP) is a direct and independent indicator of impaired bone turnover. We intended to find out whether there are any significant changes in BALP and iPTH levels, in comparison to total Ca, total Mg, inorganic P, total alkaline phosphatase (ALP), and tartrate resistant acid phosphatase (TRAP) in predialysis and dialysis patients. METHODS: Out of 266 patients investigated, 114 were on continuous ambulatory peritoneal dialysis, 112 were on maintenance haemodialysis, while 40 predialysis patients had end stage renal disease. The parameters were analysed according to the manufacturers' instructions. RESULTS: Correlations were established for the bone marker concentrations analysed among the studied groups. The largest ranges were determined for BALP and iPTH. Predialysis and dialysis patients showed very low levels of BALP. Dialysis patients had lower levels of iPTH (p < 0.001), while in predialysis patients the levels were significantly higher (p < 0.05) than recommended for low bone turnover, according to K/DOQI. CONCLUSIONS: The observations made in this study identify BALP as a good indicator of decreased bone turnover in predialysis and dialysis patients. However, in order to reveal a difference between bone activity and the level of parathyroid activity and its effect on bone turnover, it is always necessary to observe both BALP and iPTH levels.

Could the level of serum albumin be a method for assessing malnutrition in hemodialysis patients?

BACKGROUND: Traditionally, serum albumin concentration has been used for assessing the nutrition status of hemodialysis patients despite evidence that the level is also affected by inflammation and many other underlying disorders frequently present in these individuals. The authors evaluated albumin as a nutrition parameter, comparing it with more specific anthropometric parameters. METHODS: The study included a cohort of 271 patients. The analysis involved data obtained after patients entered the study (1994-2004). Anthropometric measurements included skinfolds, mid-arm circumference, mid-arm muscle circumference, percentage of body fat, body mass index, body height, and dry weight. Kt/V and normalized protein catabolic rate were also determined and laboratory analyses undertaken. RESULTS: Serum albumin was only weakly correlated with mid-arm circumference (r = 0.12), mid-arm muscle circumference (r = 0.15), and fat-free mass (r = 0.12). Common factor analysis of nutrition parameters uncovered latent variables, but serum albumin was not associated strongly with them. The sensitivity of albumin in detecting malnutrition was 24%, with a specificity of 88% and a predictive value of 74%. Graphic analysis showed disagreement in albumin levels with percentage of body fat and mid-arm muscle circumference. CONCLUSION: Serum albumin determination was shown to be a test with low sensitivity and specificity for evaluating malnutrition in hemodialysis patients. The values correlated weakly and showed graphic disagreement with anthropometric parameters. Therefore, methods that measure percentage of body fat and muscle mass should be used together or instead of serum albumin level for assessing the nutrition status of hemodialysis patients.

Preoperative preparation of patients with hyperparathyroidism as comorbidity.

Preoperative preparation of patients with hyperarathyroidism planned to be operated and/or already operated because of some other disease have specific characteristics in function of the type of hyperparathyroidism, primary or secondary. In primary hyperparathyroidism, repercussions of pronounced hypercalcemia on organs and systems are of essential importance. The most important aspect of preoperative preparation of these patients is therefore the treatment of hypercalcemia. In patients with secondary hyperparathyroidism as comorbidity, calcium level is of lesser importance since it stays mostly within reference values. Essential for perioperative preparation of these patients is the fact that they have chronic renal insufficiency and usually are on extrarenal depuration, so that uremic toxic disorders important for the perioperative course should be taken into account. Disorders caused by primary or secondary hyperparathyroidism (and terminal chronic renal insufficiency) must be brough to so-called "stable state" in elective surgical interventions. Preoperative preparation in urgent surgical interventions is focused only on vitally endangering consequences of hyperparathyroidism such as hypercalcemic crisis or extreme hyperkalemia.

Preoperative preparation of patients with renal diseases.

If patients with renal diseases had to undergo surgical intervention, they should be prepared in such a way to be in a stable phase of the underlying surgical disease, without any infection, euvolemic, with satisfactory blood pressure and corrected electrolyte balance. These patients need to be hydrated well before intervention, the fall of blood pressure during intervention should be avoided and adequate hydration after the intervention must be continued (taking into account the condition of the kidneys, heart and age of patient). It is assumed that nephrotoxic drugs are to be evaded in renal patients or, if they were necessary, the dosage and dosing interval should be adjusted and prolonged, respectively. The use of radiographic contrast is not advisable, but if required, plentiful hydration will be needed, the least workable contrast dose and, if possible, with lower ionic charge and lower osmolarity will be administered. If surgical intervention was urgent and if there was not enough time for conservative therapy, i.e., correction of electrolytes, volemia, blood pressure and higher values of nitrate substances, a renal patient would be temporarily dialyzed in the immediate preoperative and postoperative course. Any surgical intervention in these patients may aggravate the renal function and bring the patient closer to dialysis treatment. Nevertheless, sometimes the benefit of surgical treatment for the acute surgical disease is higher (especially if it was life-threatening) than the risk of renal function exacerbation and coming closer to dialysis.

Preoperative assessment of patients with end stage renal failure.

Patients with end stage renal failure (ESRF) present a number of challenges to the anesthesiologist. They may be chronically ill and debilitated and have the potential for multisystem organ dysfunction. Patients with primary renal disease are likely younger and have good cardiopulmonary reserve. Older patients with renal failure secondary to diabetes mellitus or hypertension may suffer the ravages of diffuse atherosclerosis and heart disease. To safely manage these patients we need to understand the benefits and limitations of dialysis, problems related with primary disease, pathophysiological effects of ESRF, and the altered pharmacology of commonly used anesthetic agents and perioperative medications in ESRF. Problems encountered by anesthesiologist in ESRF patients include hypertension, ischemic heart disease, congestive heart failure, anemia, metabolic acidosis, hyperkaliemia, hyponatremia and circulatory collapse. All surgical procedure in patients with ESRF carries significant risk of peri- and postoperative complications (mostly cardiovascular) and even fatal outcome.

The predictive value of anthropometric parameters on mortality in haemodialysis patients.

BACKGROUND: Since protein-calorie malnutrition is a common factor influencing morbidity and mortality of haemodialysis patients, assessing their nutritional status is important. The aim of this study was to investigate the predictive value of anthropometric parameters on mortality and their interrelationship. METHODS: The study included a cohort of 242 patients. The analysis involved baseline data obtained during the first calendar year after the patients entered the study (1994-2001) and repeated measurements for up to 132 months of follow-up (until 2004). Anthropometric measurements were made during the winter season and included skinfolds, mid-arm circumference (MAC), body height and weight. The percentage of body fat (%fat) was calculated from triceps (TSF), biceps, subscapular and suprailiac skinfolds (Disease Outcomes Quality Initiative (DOQI) guidelines) and mid-arm muscle circumference (MAMC) from MAC and TSF. Body mass index (BMI), Kt/V, normalized protein catabolic rate (NPCR) and cardiovascular co-morbidity were also determined and laboratory analyses undertaken. RESULTS: Strong correlations were found among the anthropometric parameters. Extended Cox regression analysis selected %fat, MAC, MAMC and TSF in addition to age, ischaemic heart disease, congestive heart failure, Kt/V, haemoglobin, creatinine, albumin and NPCR as potential predictors of mortality. The same anthropometric parameters were found to be independent mortality predictors in corresponding models. The most predictive anthropometric factor was MAC. BMI was not a risk factor. CONCLUSION: Percentage of body fat, MAC, MAMC and TSF were independent predictors of mortality of haemodialysis patients, and MAC was the most predictive one.

[Characteristics of neuromuscular block after administration of rocuronium bromide in patients with end-stage renal failure].

INTRODUCTION: Anaesthesia affects kidney function by reducing the renal blood flow and glomerular filtration rate. As chronic renal failure (CRF) significantly influences drug metabolism and elimination, we studied the effects of rocuronium bromide (RB) in patients with CRF. OBJECTIVE: The aim of the study was to examine whether, when using RB in patients with CFR, there are differences regarding the onset time of neuromuscular block (NMB) development, duration time, speed of recovery and cumulative effects of RB. METHODS: Prospective study included 60 patients who underwent urologic surgery procedures. The patients were divided into 3 groups: the first group (G1)--20 patients with CRF and residual dieresis, the second group (G2)--20 patients with CRF and without dieresis, and third group (G3)--20 patients with normal renal function (control group). During surgery RB was administrated for muscle paralysis in all patients. Train-of-four (TOF) Guard acceleromyography was used for NMB monitoring. RESULTS: Onset time in three groups was 132.3 s; 139.5 s and 113.2 s (p < 0.01). Duration of intubation dose was the same in G1 and G2 (28.9 minutes), while in the third group it was 27.2 minutes (p > 0.05).The number of RB repeated doses was 3-8, 3-7 and 4-8 (p > 0.05). The duration time until spontaneous recovery was 31.8, 31.6 and 29.8 minutes (p > 0.01). The recovery index was 16.8,16.7 and 10.6 minutes (p < 0.001). The duration time from the last dose of RB to extubation was 74.5, 74.8 and 58.9 minutes (p < 0.001). CONCLUSION: In patients with CRF the cumulative effect of the drug was registered, with a prolonged recovery time from NMB in relation to the patients with normal renal function.

Cyclosporine versus azathioprine therapy in high-risk idiopathic membranous nephropathy patients: A 3-year prospective study.

There is no consensus regarding the modality of therapy for idiopathic membranous nephropathy (IMN), especially for patients who did not react to treatment with cytotoxic drugs. This study followed prospectively for 3-year IMN patients who did not react to Ponticelli protocol comparing effects of 2-year course of cyclosporine (CsA) with azathioprine (Aza) treatment both with small doses of prednisolone. Twenty-three patients were randomly assigned to receive either cyclosporine at 3mg/kg per day (10 patients) or azathioprine at 1.5 to 2mg/kg (13 patients). Both groups were comparable regarding age, sex and renal function, except for proteinuria, which was significantly greater in CsA group (P=0.003). Similar rate of remission of nephrotic syndrome (NS) have been noted at the end of treatment (80% CsA versus 93% Aza). During last year, follow-up relapses of NS were more frequent in Aza group (5 versus 1). A fall in proteinuria was recorded in both groups during treatment, but it rose significantly in Aza group (1.5g/day versus 3.1g/day, P=0.04) and remained unchanged in CsA group (3.9g/day versus 4.1g/day) after treatment cessation. Renal function deteriorated in Aza group (sCr 120.5 versus 269.8µmol/L; P<0.01) and was stable in CsA group. In conclusion, CsA and steroids may be a very important option in the management of high-risk IMN patients. Long-term treatment is necessary for achievement of full therapeutic effect. Treatment with Aza did not have long-term benefits particularly regarding renal function preservation.

[Risk factors for the development of diabetic nephropathy].

INTRODUCTION: Results of epidemiological analysis show that one third of patients with diabetes mellitus develop diabetic nephropathy (DN). Strategies used until now to slow down the progression of DN were initiated when the symptoms of DN were already present. OBJECTIVE: Our objective was to analyze the prevalence and characteristics of DN and to determine the factors leading to DN. METHODS: Fifty-two patients with diabetes mellitus (DM)--32 with type 1 aged 32 years and 20 with type 2 aged 59 years--were referred from the Institute of Endocrinology, Diabetes and Metabolic Diseases to the Department of Nephrology for kidney function evaluation. Apart from routine laboratory analyses, glomerular filtration rate was calculated using the MDRD formula (modification of diet in renal disease), the size of the kidney was measured by ultrasound, and kidney volume was calculated using the ellipsoid formula. RESULTS: Thirty percent of the patients revealed normal (eight patients with DM type 1) or satisfactory kidney function (eight patients with DM type 1) with physiological proteinuria. Microalbuminuria (MAU) or pathological proteinuria (PRT) were found in 10 and 9 patients, respectively, with DM type 1, while decreased kidney function was found in one patient without proteinuria. MAU or PRT were found in four and eight patients, respectively, with DM type 2 and decreased kidney function in four patients without proteinuria. Kidney function was significantly lower in patients with DM type 2 in comparison to DM type 1, while the patients with decreased kidney function had a higher PRT. Compared to DM type 2, in DM type 1 patients, the kidney was longer, and parenchymal artery resistance index was lower in DM type 1 patients compared to DM type 2. Factors associated with DN were patient's age, duration of diabetes, systolic blood pressure, HbA1c and kidney volume. CONCLUSION: The prevalence of DN among the studied patients was 70%. Treatable factors associated with the development of DN are strict control of blood pressure and glycaemia control.

Polyneuropathy in diabetic and nondiabetic patients on CAPD: is there an association with HRQOL?

BACKGROUND: It is well known that patients with uremia, as well as patients with diabetes mellitus, develop polyneuropathy. OBJECTIVES: The signs of polyneuropathy in diabetic and nondiabetic patients on continuous ambulatory peritoneal dialysis (CAPD) and their relation with age, duration of dialysis, biochemical parameters, dialysis adequacy, and health-related quality of life (HRQOL) were analyzed in the present study. PATIENTS AND METHODS: 65 CAPD patients (37 men, age 29-85 years, duration on dialysis 3 months to 14 years) were divided into two groups: group 1 was comprised of 20 diabetic patients (mean age 50.1+/-13.2 years); group 2 was comprised of 45 nondiabetic patients (mean age 62.3+/-9.7 years). Biochemical parameters, dialysis adequacy, and clinical signs were determined. Motor conduction velocity on the peroneal and tibial nerves and sensitive conduction velocity on the sural nerve were measured. The Kidney Disease Quality of Life Short Form (KDQOL-SF) was used to measure the CAPD patients' self-assessment of functioning and well-being using 4 component scores: physical component summary (PCS), mental component summary (MCS), kidney disease target issues, and patient satisfaction. RESULTS: Subjective symptoms were more intense in the diabetic patients and correlated with changes in peroneal and tibial distal motor latency (DML). Diabetic patients were significantly younger, had lower creatinine and higher glucose levels, and all analyzed pathological neurophysiological parameters were higher. Nondiabetic patients had prolonged latency of the F-wave on the peroneal nerve and the tibial nerve and reduced sensitive conduction velocity on the sural nerve. Significant correlations were found between the analyzed neurophysiological parameters and duration of dialysis and diabetes, glucose concentration, and dialysis adequacy in diabetic patients, and between neurophysiological parameters and age and dialysis adequacy in nondiabetic patients. Analysis of the 4 component scores of the KDQOL-SF revealed that diabetic patients had significantly better scores for PCS and MCS, which can be explained by their younger age. Patient satisfaction was worse in diabetic patients and correlated with duration of diabetes. In addition, significant correlations were established between PCS, MCS, and tibial DML (late neuropathic changes) in diabetic patients, and between MCS and tibial F-wave (early neuropathic changes) in nondiabetic patients. CONCLUSION: Polyneuropathy was significantly worse in diabetic than in nondiabetic patients on CAPD. DML on the tibial nerve correlated with glucose concentration, dialysis adequacy, PCS, and MCS in diabetic patients, whereas in nondiabetic patients, dialysis adequacy and azotemia correlated with F-waves on the peroneal nerve and the tibial nerve but MCS only with F-wave on the tibial nerve.