Renal Disturbances during and after Radioligand Therapy of Neuroendocrine Tumors-Extended Analysis of Potential Acute and Chronic Complications.

Neuroendocrine tumors (NEN) are a group of neoplasms that arise from hormonal and neural cells. Despite a common origin, their clinical symptoms and outcomes are varied. They are most commonly localized in the gastrointestinal tract. Targeted radioligand therapy (RLT) is a treatment option which has proven to be successful in recent studies. However, the possible outcomes and true safety profile of the treatment need to be fully determined, especially by new, more sensitive methods. Our study aimed to present an extended analysis of acute and chronic renal complications during and after radioligand therapy using, for the first time in the literature, innovative and complex renal parameters. Forty patients with neuroendocrine tumors underwent four courses of radioligand therapy with [177Lu]Lu-DOTATATE or [177Lu]Lu/[90Y]Y-DOTATATE. Radioisotopes were administrated in intervals of 8-12 weeks, with concurrent intravenous nephroprotection. New detailed and sensitive renal parameters were used to determine the renal safety profile during and after radioisotope therapy for standard treatment of NEN. During the first and fourth courses of RLT, no change in the glomerular filtration rate (GFR) was observed. However, long-term observations one year after the treatment showed a 10% reduction in the GFR. During the first course of treatment, the fractional urea and calcium excretions increased, while the fractional potassium concentration decreased. The fractional calcium excretion remained highly increased in long-term observations. Decreases in urine IL-18, KIM-1 and albumin concentrations were observed during RLT. The concentrations of IL-18 and KIM-1 remained low even a year after therapy. The ultrasound parameters of renal perfusion changed during treatment, before partially returning to the baseline one year after therapy, and were correlated with the biochemical parameters of renal function. A permanent increase in diastolic blood pressure was correlated with the decrease in the GFR observed during the study. In this innovative and complex renal assessment during and after RLT, we found a permanent 10% per year decrease in the GFR and noticeable disturbances in renal tubule function. The diastolic blood pressure also increased.

Comparison of the Color Doppler Vascularity Index in Patients with Pancreatic Adenocarcinoma and Chronic Pancreatitis from a Single Center in Poland.

BACKGROUND Pancreatic cancer is one of the most common cancers in the world and a major cause of cancer mortality. Therefore, it is extremely important to distinguish between malignant and benign changes quickly and accurately. This single-center study aimed to assess the discriminatory properties of the color Doppler vascularity index (CDVI) in the diagnosis of focal chronic pancreatitis and malignant pancreatic tumors. MATERIAL AND METHODS Seventy-nine patients (42 men, 37 women; age 62.0±13.5 years; 46 adenocarcinomas; 33 pancreatitis) qualified for this study. During endosonographic examination, pancreatic tumors were assessed in the color Doppler option. The dynamic tissue perfusion measurement was used to calculate tissue flow velocity (TFV), tissue perfusion intensity (TPI), and vascularization as the CDVI. RESULTS TFV, TPI, and CDVI were significantly lower in the group with malignant tumors than in the group with pancreatitis (P<0.001). In the receiver operating characteristic analysis, results of TFV=2.181 cm/s, TPI=0.009 cm/s, and CDVI=0.268 allowed for significant prediction of malignant tumors (P<0.001), with sensitivity of 75.8%, 69.7%, and 72.7% and specificity of 91.3%, 93.5%, and 80.4%, respectively, without significant differences between perfusion parameters and CDVI (P=0.07). CONCLUSIONS The findings from this study showed that color Doppler imaging and the use of the CDVI could provide an adjunctive diagnostic approach to distinguish between pancreatic adenocarcinoma and focal chronic pancreatitis. Owing to the possibility of calculating vascularization by non-Doppler methods, the method may be an easier and more accessible diagnostic option for malignant pancreatic tumors than perfusion assessed in external software.

Renal Cortical Perfusion Estimated in Color Doppler Dynamic Tissue Perfusion Measurement in Patients Treated with Levothyroxine Following Total Thyroidectomy for Resectable Thyroid Cancer Is Independently Associated with Free Thyroxine: A Single-Center Prospective Study.

BACKGROUND The thyroid state significantly influences renal function. However, a direct link between thyroid and kidney dysfunction has not been identified. Thyroid hormones affect cardiac output and vascular resistance, and thus can modify kidney perfusion. This prospective study aimed to test the association between renal cortical perfusion (RCP) estimated in color Doppler sonographic dynamic tissue perfusion measurement (DTPM) with thyroid hormones in 36 patients treated with levothyroxine following total thyroidectomy for resectable thyroid cancer. MATERIAL AND METHODS Blood tests, blood pressure monitoring, and DTPM of the renal cortex were performed. To exclude possible reading errors, the intrarater reliability of the ultrasound perfusion measurement method was estimated. RESULTS The absolute difference between the 2 ultrasound RCP measurements was 5.2±4.4%. RCP correlated significantly with free thyroxine (FT4) (r=0.46; p=0.006) but not with triiodothyronine and thyroid-stimulating hormone. In the adjusted to age backward stepwise multivariable regression analysis model, including estimated glomerular filtration rate, mean arterial pressure, and FT4, only FT4 was independently associated with RCP (R²=0.21; p=0.006). CONCLUSIONS Renal cortical perfusion is independently associated with free thyroxine, which can contribute to renal function abnormalities in the condition of impaired thyroid function. This small prospective study from a single center showed that the renal cortex's color Doppler sonographic dynamic tissue perfusion measurement had very good intraobserver reproducibility.

Influence of disease severity and cardiac autonomic tone on ventricular repolarization and dispersion in electrocardiographic assessment of patients with systemic lupus erythematosus.

BACKGROUND: There are no data on the influence of disease severity and cardiac autonomic tone on ventricular repolarization and dispersion in 24-hour Holter monitoring in systemic lupus erythematosus (SLE). METHODS: Consecutive 92 SLE and 51 healthy subjects were studied. The standard 12-lead electrocardiography (ECG), Holter monitoring with heart rate turbulence (HRT) and QT, Tp-e and Tp-e/QT ratio assessment (including corrected values) were performed. Subjects with conditions causing repolarization abnormalities or insufficient number of beats suitable for QT evaluation were excluded (17 SLE and 8 controls). RESULTS: Finally, 75 SLE and 43 sex- and age-matched controls were included to the study. In SLE patients, the median disease severity score (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)) was 3.0. The mean values of QTc, cTp-e and cTp-e/QTc were significantly higher in SLE patients than in controls. QTc ≥ 460 ms was observed in 18.7% of patients using standard ECG and in 58.7% using Holter monitoring. With Holter monitoring, patients with SLICC/ACR-DI >3.0 presented longer QTc than those with SLICC/ACR-DI ≤3.0 (418±15 vs. 409 ± 16, p = 0.04), while cTp-e and cTp-e/QTc values were similar. Patients with abnormal HRT presented longer cTp-e and higher cTp-e/QTc than those with normal HRT (92 ± 52 vs. 71 ± 16 ms, p = 0.04; 0.244 ± 0.126 vs. 0.187 ± 0.035, p = 0.03), while QTc values were similar. No differences in QT and Tp-e parameters were observed according to disease duration. CONCLUSION: In SLE patients, Holter monitoring revealed QTc prolongation more frequently than standard ECG. Longer QTc values were observed in patients with more advanced disease, while increased cTp-e and cTp-e/QTc were related to cardiac autonomic dysfunction expressed by abnormal HRT.

THE ROLE OF PET/CT WITH 11C-METHIONINE IN CONTEMPORARY NUCLEAR MEDICINE.

OBJECTIVE: Positron emission tomography (PET/CT) is a non-invasive molecular imaging technique using isotopes with a short half-life usually in combination with chemical compounds. The most commonly used PET/CT tracer is 2-fluoro-2-deoxy-D-glucose labeled with fluorine (18-FDG). It is used mainly in oncological diagnostics as well as myocardial viability, epilepsy and inflammatory diagnostics. The tracer less commonly used in PET/CT could be carbon-labeled methionine (11C-MET). It is mainly used in the diagnosis of focal lesions in the central nervous system. There are also reports of the use of this tracer in diagnostics of the primary, secondary and tertiary hyperparathyroidism as well as multiple myeloma. This tracer may also be used in the diagnosis of lymphoproliferative diseases and solid tumors, although there is no clear evidence of its advantage over 18-FDG. CONCLUSION: Conclusion: Significant difficulties in the production and transport of this tracer and lack of reimbursement of this type of procedure in Poland limits the use of this tracer for scientific research.

Common atherosclerosis genetic risk factors and subclinical atherosclerosis in rheumatoid arthritis: the relevance of disease duration.

Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by increased cardiovascular morbidity. Several previous studies assessed associations between common atherosclerotic genetic risk factors and subclinical atherosclerosis (SA) in RA patients, yet most of them gave negative results. We undertook a cross-sectional study to evaluate the association between previously reported SNPs and subclinical atherosclerosis in a cohort of Polish RA patients. 29 SNPs associated with atherosclerosis in general population were genotyped in 289 RA patients: 116 patients with SA (increased carotid intima-media thickness and/or presence of carotid plaque) and 173 patients without SA. To assess the cumulative effect of SNPs we calculated 3 weighted genetic risk scores: GRSIMT, GRSCP and GRSCAD, comprising intima-media thickness-associated SNPs, carotid plaque-associated SNPs and coronary artery disease-associated SNPs, respectively. None of the SNPs showed a significant association with SA. However, we found an association between SA and GRSIMT. Interestingly, this association was limited to patients with short disease duration (P = 0.00004 vs. P > 0.5, for comparison of GRSIMT among patients within the 1st quartile of disease duration vs. others, respectively). Patients within the 1st quartile of disease duration were more frequently disease modifying anti-rheumatic drugs (DMARDs)-naïve and less frequently treated with biologics. Our study suggests that in patients with early RA subclinical atherosclerosis may be driven by similar genetic factors as in general population, while in long-lasting disease, the role common genetic risk factors may decrease. Possibly, this effect may be due to the influence of DMARDs.

Comparison of non-invasive assessment of arrhythmias, conduction disturbances and cardiac autonomic tone in systemic sclerosis and systemic lupus erythematosus.

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are connective tissue diseases presenting cardiac complications including different arrhythmias, then direct electrocardiographic comparison may be useful in everyday clinical decision making. We examined 86 adult SSc patients, 76 with SLE and 45 healthy controls. Among other examinations all subjects underwent 24-h Holter monitoring with time-domain heart rate variability and heart rate turbulence evaluation. Patients with various co-existing conditions which might markedly influence arrhythmias and autonomic modulation were excluded from further analysis (SSc n = 12, SLE n = 6). Finally, 76 SSc and 70 SLE subjects were eligible for this study, mean age 51.9 ± 13.1 and 46.5 ± 12.7 years (p = 0.11), with median disease duration 6.0 and 8.5 years (p = 0.15), respectively. As compared to SLE, patients with SSc were characterised by more frequent incidence of various supraventricular and ventricular arrhythmias. As compared to SSc, patients with SLE presented prolonged corrected QT intervals and also significant correlations between corrected QT length and heart rate variability indices. Both SSc and SLE subjects presented impaired sympathetic cardiac autonomic modulation, while indices associated with parasympathetic activity in SLE were not diminished. Disease duration was not associated with arrhythmias' occurrence (except for ventricular tachycardia in SSc, p = 0.02) and also with autonomic function in both groups of patients. Patients with SSc and SLE differ in terms of arrhythmias, conduction disturbances and cardiac autonomic tone. Regular Holter monitoring should be considered as a part of routine evaluation in connective tissue diseases patients, especially in systemic sclerosis.

Elastography in the Diagnosis of Pancreatic Malignancies.

The study aimed to determine the usefulness of the elastography in the diagnosis of malignancy of solid pancreatic tumors. There were 123 patients (F/M; 51/72, aged 62 ± 14) enrolled into the study with the diagnosis of pancreatic masses. Malignant pancreatic adenocarcinoma was identified in 78 patients and an inflammatory mass corresponding to chronic pancreatitis in the remaining 45 patients. The mass elasticity of a tumor (A-elasticity) and a reference zone (B-elasticity) and the B/A strain ratio were measured. All these elastographic parameters differed between groups and correlated significantly with malignancies (r = 0.841; r = -0.834; r = 0.487, respectively). Receiver operating characteristic (ROC) analysis showed that A-elasticity between 0.05% and 0.14% alone, as well as the B/A strain ratio between 7.87 and 18.23 alone, enabled the recognition of all malignant pancreatic tumors with 100% sensitivity and ≥ 97.8% specificity. Surprisingly, B-elasticity alone also was helpful in recognizing malignant tumors (71% sensitivity, 80% specificity, 0.74 accuracy, and 0.792 area under the curve), although it appeared worse than A-elasticity and B/A strain ratio (p < 0.001). In multivariable regression analysis, A-elasticity identified 89.5% of malignancies (p < 0.001). A-elasticity and B-elasticity were the only significant independent factors influencing the tumor identification (r2 = 0.927; p < 0.001). The assessment of tumor elasticity appears sufficient to identify malignant tumors of the pancreas.

Copeptin Blood Content as a Diagnostic Marker of Chronic Kidney Disease.

Plasma content of copeptin increases with the advancement of chronic kidney disease (CKD). The purpose of this study was to evaluate copeptin content as a potential marker of CKD, as a single pathology or with coexisting heart failure. Seventy-six patients were divided into the following groups: Group 1 (control), without CKD and heart failure; Group 2, CKD stage 3a; Group 3, CKD stage 3b; Group 4, CKD stage 4; Group 5, CKD stage 5; and Group 6, CKD stage 3b and heart failure. For all patients, plasma concentrations of copeptin, creatinine, urea, cystatin C, sodium, C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and blood pH were assessed. We found that plasma content of creatinine, urea, CRP, cystatin, NT-proBNP, and copeptin increased with CKD progression. Heart failure in CKD patients was not the cause of an appreciable increase of copeptin level. Copeptin/creatinine, copeptin/cystatin C ratios, and especially copeptin/eGFR ratio enhanced copeptin prognostic sensitivity concerning renal failure in CKD, compared with copeptin alone. The copeptin×NT-proBNP ratio decreased along CKD progression, reaching a nadir in the accompanying heart failure. In contradistinction, copeptin×NT-proBNP/creatinine ratio increased along CKD progression, reaching a peak in the accompanying heart failure. We conclude that copeptin is an important marker in CKD, but not so concerning heart failure in the disease. A decrease in copeptin×NT-proBNP and an increase in copeptin×NT-proBNP/creatinine ratio are useful markers of cardiac function decline in CKD.

[Current treatment of neuroendocrine tumors].

Neuroendocrine neoplasms (NEN) are group of rare neoplasms, which frequency is estimated on about 35 cases/100000. Though, during last 30 years the number of NEN new cases increased five-times. Nowadays the only method which allows to cure NEN is surgical treatment. Laparoscopic surgery and endoscopic treatment are also used. These neoplasms are usually diagnosed in advanced stadium, with distant metastases, when surgery is not an option. In this group of patients systemic and local therapies are used, such as somatostatin analogues, chemotherapy or targeted therapy. The choice of proper method is determined not only by neoplasm's localization or its size, but also clinical symptoms caused by tumor itself or by substations released by it. One place hopes in novel molecular-based therapies and currently investigated therapies using i.a. oncolytic viruses.

[WSPÓLCZESNA DIAGNOSTYKA NOWOTWORÓW NEUROENDOKRYNNYCH Current diagnostics of neuroendocrine tumors].

Neuroendocrine tumors (NEN) are rarely diagnosed neoplasms, which frequency is estimated on about 35 cases/100 000. During last 30 years the number of NEN's new diagnosis increased five-times and nowadays reaches 5,86/100 000/year. It is partially associated with increasing detectability of these tumors. Such diagnostic methods as capsule endoscopy and positron emission tomography are becoming increasingly widely accessible. Though, one should bear in mind that in case of patients diagnosed with NEN cooperation between specialists in different fields of medicine, such as endocrinology, nuclear medicine, oncology, radiology, internal medicine and surgery is needed.

[Treatment of neuroendocrine tumors with radio-labeled somatostatin analogues].

There is a steady increase in the number of neuroendocrine tumors. Although the knowledge about this tumors' biology is increasing, they are still diagnosed in advanced stadium, when surgical treatment is not an option. One of the treatment methods which are available in this group of patients is peptide receptor radionuclide therapy, which should be considered in selected patients. This treatment is usually well tolerated by patients, though severe adverse events may occur, such as myelosuppression or renal failure.

Role of Nitric Oxide Pathway in Development and Progression of Chronic Kidney Disease in Rats Sensitive and Resistant to its Occurrence in an Experimental Model of 5/6 Nephrectomy.

BACKGROUND Understanding the mechanisms conditioning development of chronic kidney disease (CKD) is still a challenge. The aim of this study was to evaluate the activity of the intrarenal nitric oxide (NO) pathway in the context of sensitivity or resistance of different animal strains to the development and degree of renal failure. MATERIAL AND METHODS Two rat strains were used: Wistar (WR) and Sprague-Dawley rats (SDR) in a model of CKD - 5/6 nephrectomy. We assessed parameters of renal failure and expression of nitric oxide synthase (NOS) isoforms in renal cortex and medulla. RESULTS We did not observe renal failure in WR, and CKD developed in SDR with increase of creatinine and urea concentration as well as decrease of diuresis and glomerular filtration. In the renal cortex, baseline expression of NOS2 was higher in WR than in SDR. 5/6 nephrectomy resulted in reduction of NOS2 in both strains and NOS3 in WR. In the renal medulla, baseline NOS2 expression was higher in SDR, and nephrectomy resulted in its decrease only in SDR. Although baseline NOS3 expression was higher in SDR, the NOS3 expression after nephrectomy was higher in WR rats. CONCLUSIONS In model of CKD - 5/6 nephrectomy, SDR proved to be sensitive and WR resistant to development of CKD. The intrarenal activity of the nitric oxide pathway was the factor that differentiated both strains. This mechanism may be responsible for insensitivity of WR to development of renal failure in this model of CKD.

[The influence of hypothyroidism on the conversion and binding of thyroid hormones in patients with end-stage renal disease]. / Wplyw niedoczynnosci tarczycy u chorych ze schylkowa niewydolnoscia nerek na wspólczynniki konwersji i wiazania hormonów tarczycy.

Hypothyroidism in patients with renal failure (RF) causes many metabolic and clinical problems, and both these diseases can mutually exacerbate their disturbances. AIM: The aim of this study was to evaluate the effect of hypothyroidism, and end-stage renal disease (ESRD) on conversion of thyroid hormones (TH) in patients with ESRD treated with chronic hemodialysis (HD). MATERIALS AND METHODS: The study was performed in 74 patients, including 41 women (K) and 33 men (M) aged 28-83 y.o. in 4 groups: G1 - 12 people with ESRD treated with HD and with newly diagnosed hypothyroidism without substitution (6 K and M 6) aged 66,83±12,90 y.o., G2 - 26 patients with ESRD treated with HD without hypothyroidism (10 F, 16 M) aged 58,85±15,52 y.o., G3 - 11 hypothyroid patients without RF (9 K, 2 M) aged 54,73±21,26 y.o., G4 - 25-persons from control group of healthy subjects (16 M, 9 M) aged 51,24±12,58 y.o. In all subjects the concentration of TSH and TH (T4, T3, fT4, TSH, FT3, rT3) were measured and values of conversion factors (T3/T4, FT3/ fT4, rT3/fT4 and rT3/fT3) and binding TH to protein factors (fT4/T4 and fT3/T3) were calculated. RESULTS: Lower concentration of T3 (p=0.012), fT3 (p<0.001) i fT4 (p=0.014) was found in patients without hypothyroidism than in healthy subjects. Renal failure with concomitant hypothyroidism intensify the disturbances of T4 to T3 conversion (p=0.034) and hypothyroidism with concomitant renal failure disrupts binding of T3 to proteins (p=0.001). FT3 to fT4 ratio in renal failure with concomitant hypothyroidism group was significantly lower than in each other group. rT3 concentrations were the highest in healthy subjects. CONCLUSIONS: Concomitance of hypothyroidism and end-stage renal disease reduces the conversion of thyroxine to triiodothyronine, but does not increase the production of rT3. Hypothyroidism significantly increases the disorders of thyroid hormones in end-stage renal disease. There is decreased tendency to bind of thyroid hormone to protein in hypothyroidism in patients with end-stage renal disease.

[Hereditary pancreatitis]. / Dziedziczne zapalenie trzustki.

Hereditary pancreatitis (HP) is a rare, heterogeneous familial disease and should be suspected in any patient who has suffered at least two attacks of acute pancreatitis for which there is no underlying cause and unexplained chronic pancreatitis with a family history in a first- or second degree relative. with an early onset, mostly during childhood. Genetic factors have been implied in cases of familial chronic pancreatitis. The most common are mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). The inflammation results in repeated DNA damage, error-prone repair mechanisms and the progressive accumulation of genetic mutations. Risk of pancreatic adenocarcinoma is a major concern of many patients with hereditary chronic pancreatitis, but the individual risk is poorly defined. Better risk models of pancreatic cancer in individual patients based on etiology of pancreatitis, family history, genetics, smoking, alcohol, diabetes and the patient's age are needed.

[Autoimmune pancreatitis as an element of autoimmune polyglandular syndrome]. / Autoimmunologiczne zapalenie trzustki jako skladowa autoimmunologicznego zespolu wielogruczolowego.

Autoimmune pancreatitis constantly belongs to diseases which often causes significant diagnostic problem and often runs out with surgical intervention as considered to be a pancreatic cancer. Important although usually underestimated problems are polyglandular syndromes, which may consist of autoimmune pancreatitis (AIP) problem as well. This case report is an example of autoimmune polyglandular syndrome (APS), which was connected with the surgical treatment with biliary bypass anastomosis because of the unresectable lesion in the head of pancreas. The definite remission of the pancreatic lesion finally came after a steroid therapy. Differentiation between neoplastic and inflammatory pancreatic tumors very often remains a serious clinical problem. On grounds of imaging and cytopathology exams it is often difficult to decide about the nature of a lesion. The negative result of cytopathological biopsy examination does not finally settle straightforward diagnosis. Diagnostic problems affect also autoimmune pancreatitis. It is worth to undertake attempts to differentiate pancreatic lesions especially in cases of concomitance with other autoimmune polyglandular syndromes. That is because it is connected with completely different treatment and outcome. We should remember about diagnostic criteria of autoimmune pancreatitis. Appropriate diagnosis for patients with AIP gives them a chance to avoid serious surgical resection and possible complications.

Is Free Testosterone Concentration a Prognostic Factor of Survival in Chronic Renal Failure (CRF)?

BACKGROUND: Lowered testosterone level in CRF patients is associated with elevated risk of death due to cardiovascular reasons, and is influenced by many factors, including acid-base balance disorders. AIMS: evaluation of testoste-rone concentration (TT) and free testosterone concentration (fT) in pre-dialysis and dialysis patients; assessment of TT and fT relationships with biochemical parameters; evaluation of prognostic importance of TT and fT in predicting patient survival. MATERIAL AND METHODS: 4 groups of men: 14 - on hemodialysis (HD), 13 - on peritoneal dialysis (PD), 9 - with chronic renal failure (CRF) and 8 - healthy (CG), aged 56±17, 53±15, 68±12, 43±10 years, respectively. TT and biochemical para-meters were measured; fT was calculated. RESULTS: The lowest TT and fT were observed in HD and CRF, the highest - in CG (p=0.035 for TT; p=0.007 for fT). fT in CRF and CG were different (p=0.031). TT and age was associated in HD (p=0.026). Age and fT was strongly associated in PD (p<0.001). After adjustment for age, TT was negatively associated with BMI (p=0.013) and fT was positively associated with HCO3 level (p=0.007). fT was lower in those who died during 5 years of observation than in survivors (p=0.009). We have found that, opposite to TT, fT appeared to be a better predictor of 5-year survival than age. After combining pH and HCO3 levels into a single variable - no acidosis, acidosis with HCO3 normal serum level, acidosis with low concentrations of HCO3 and adjustment for age and the study group - a trend toward the lowest values of free testosterone in decompensated acidosis was observed (ptrend=0.027). Such a trend was not seen for testosterone concentrations (ptrend=0.107). CONCLUSIONS: Total and free testosterone levels were lower in HD and pre-dialysis than in healthy patients. Free testost-erone level may predict long-term survival better than age. Total and free testosterone levels are lower in metabolic acidosis and total and free testosterone levels were positively associated with HCO3 level.

D-Galactosamine Intoxication in Experimental Animals: Is it Only an Experimental Model of Acute Liver Failure?

BACKGROUND: Short-term administration of Galactosamine to experimental animals causes liver damage and acute liver failure (ALF), as well as acute renal failure in some cases. The aim of our study was to describe kidney disorders that developed in the course of galactosamine-induced liver failure. MATERIAL AND METHODS: Sprague-Dawley rats were randomly divided into 2 groups: a study group administered galactosamine intraperitoneally and a control group administered saline. RESULTS: All the animals in the study group developed liver damage and failure within 48 h, with significant increase of alanine (p<0.001), aspartate aminotransferases (p<0.0001), bilirubin (p<0.004), and ammonia (p<0.005) and decrease of albumin (p<0.001) concentrations. Acute renal failure was observed in all test animals, with a significant increase in creatinine (p<0.001) and urea (p<0.001) concentrations and a decrease in creatinine clearance (p<0.0012). Moreover, osmotic clearance (p<0.001), daily natriuresis (p<0.003), and fractional sodium excretion (p<0.016) decreased significantly in this group of animals. The ratio of urine osmolality to serum osmolality did not change. Histopathology of the liver revealed massive necrosis of hepatocytes, whereas renal histopathology showed no changes. CONCLUSIONS: Acute renal failure that developed in the course of galactosamine-induced ALF was of a functional nature, with the kidneys retaining the ability to concentrate urine and retain sodium, and there were no renal changes in the histopathological examination. It seems that the experimental model of ALF induced by galactosamine can be viewed as a model of hepatorenal syndrome that occurs in the course of acute damage and liver failure.

First year survival of patients on maintenance dialysis treatment in Poland.

Retrospective analysis of demographic and clinical data of all patients starting dialysis over two years in our Department (n = 105) has been conducted. Factors such as type of dialysis treatment, reason of end-stage renal disease, Body Mass Index (BMI), laboratory tests results, number and cause of death during first year of dialysis were taken under consideration. Five patients have been excluded from the analysis of mortality (four received renal transplantation, one changed dialysis center). Twenty tree deaths have been noted during first year of dialysis treatment. Nine of them occurred during the first three months of therapy. The leading cause of death was cardio-vascular events (n = 14, 60.9%), the second was malignancy (8, 34,8%), one patient died due to catheter associated infection. Malignancy as a cause of end-stage renal disease, lack of outpatient nephrology care, acute mode of beginning renal replacement therapy and lack of erythropoiesis stimulating agents therapy were associated with higher risk of all-cause mortality during first year of dialysis. Being under the outpatient nephrology care, etiology of ESRD other than malignancy and erythropoiesis stimulating agents therapy were independently associated with better survival during this period of time. Other independent variables did not reach statistical significance. To conclude, in order to improve one year survival of dialysis patients, outpatient nephrology care with adequate amount of visits and associated dialysis therapy should be employed.

Systemic lupus erythematosus: the influence of disease-related and classical risk factors on intima media thickness and prevalence of atherosclerotic plaques--a preliminary report. Beneficial effect of immunosuppressive treatment on carotid intima media thickness.

OBJECTIVE: The risk of cardiovascular disease is increased in systemic lupus erythematosus (SLE). A meta-analysis showed increased carotid intima media thickness (IMT) in SLE. The aim of this study was to assess the influence of different SLE characteristics and treatment regimens on IMT and atherosclerotic plaques. METHODS AND RESULTS: One hundred and three SLE patients and 95 age- and sex-matched control subjects were included in the study. MT was measured in the common carotid arteries bilaterally. Common carotid arteries, internal carotid arteries and superficial femoral arteries were also screened for the presence of plaques. The presence of plaques was correlated with age (P = 0.00002), male sex (P = 0.034), Framingham 10-year risk score (P < 1 x 10(-6)), SLE duration (P = 0.00006), lack of immunologic disorder (P = 0.0014) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (P = 0.049). IMT was associated with SLE duration (P = 0.002), body mass index (P = 0.026), Framingham 10-year risk score (P < 0.001), total cholesterol concentration (P = 0.002), LDL cholesterol concentration (P = 0.007), SLICC/ACR (P = 0.035), hypertension (P = 0.002), immunologic disorder (P = 0.00008) and discontinuous treatment with immunosuppressive drugs (P = 0.043). CONCLUSIONS: We found a correlation between atherosclerosis and several classical cardiovascular risk factors and disease-related factors. A beneficial effect of continuous immunosuppressive treatment on IMT suggests that appropriate disease control with steroid-sparing agents may protect against atherosclerosis in SLE patients.