Population exposure-response model of 131I in patients with benign thyroid disease.

PURPOSE: The study aimed to explore the relationship of different exposure measures with 131I therapy response in patients with benign thyroid disease, estimate the variability in the response, investigate possible covariates, and discuss dosing implications of the results. METHODS: A population exposure-response analysis was performed using nonlinear mixed-effects modelling. Data from 95 adult patients with benign thyroid disease were analysed. Evaluated exposure parameters were: administered radioactivity dose (Aa) [MBq], total absorbed dose (ABD) [Gy], maximum of absorbed dose-rate (MXR) [Gy/h] and biologically effective dose (BED) [Gy]. The response was modelled as ordered categorical data: hyper-, eu- and hypothyroidism. The final model performance was evaluated by a visual predictive check. RESULTS: The probability of the outcome following 131I therapy was best described by a proportional-odds model, including the log-linear model of 131I effect and the exponential model of the response-time relationship. All exposure measures were statistically significant with p<0.001, with BED and ABD being statistically better than the other two. Nevertheless, as BED resulted in the lowest AIC value, it was included in the final model. Accordingly, BED value of 289.7 Gy is associated with 80% probability of successful treatment outcome 12 months after 131I application in patients with median thyroid volume (32.28 mL). The target thyroid volume was a statistically significant covariate. The visual predictive check of the final model showed good model performance. CONCLUSION: Our results imply that BED formalism could aid in therapy individualisation. The larger thyroid volume is associated with a lower probability of a successful outcome.

Investigation of factors influencing radioiodine (131I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach.

PURPOSE: Radioiodine (131I) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize 131I biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal 131I kinetics by developing a population model. METHODS: Population pharmacokinetic analysis was performed using a nonlinear mixed effects approach. Data sets of 345 adult patients with benign thyroid disease, retrospectively collected from patients' medical records, were evaluated in the analysis. The two-compartment model of 131I biokinetics representing the blood compartment and thyroid gland was used as the structural model. RESULTS: Results of the study indicate that the rate constant of the uptake of 131I into the thyroid (ktu) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT4), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of 131I is affected by the age of the patients. Inclusion of the covariates in the base model resulted in a decrease of the between subject variability for ktu from 91 (3.9) to 53.9 (4.5)%. CONCLUSIONS: This is the first population model that accounts for the influence of fT4 and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to 131I and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.

Homocystein as a risk factor for developing complications in chronic renal failure.

AIM: Cardiovascular diseases are leading cause of death in patients with chronic renal failure. The aim of our study was to establish connection between levels of homocysteine and traditional and nontraditional risk factors for developing cardiovascular diseases in dialysis and pre dialysis patients. METHODS: We included 33 pre dialysis (23 in stage three and 10 in stage four of chronic kidney disease) and 43 patients receiving hemodialysis longer than six months. Besides standard laboratory parameters, levels of homocysteine and blood pressure were measured in all patients. Glomerular filtration rate was measured in pre dialysis patients and dialysis quality parameters in dialysis patients. RESULTS: Homocysteine levels were elevated in all patients (19±5.42mmol/l). The connection between homocysteine levels and other cardiovascular diseases risk factors was not established in pre dialysis patients. In patients treated with hemodialysis we found negative correlation between homocysteine levels and patients' age (p<0.05) and positive correlation between homocysteine levels and length of dialysis (p<0.01) as well as between homocysteine and anemia parameters (erythrocytes, hemoglobin), (p<0.01). Homocysteine and LDL (and total cholesterol) were in negative correlation (p<0.01). CONCLUSION: Homocysteine, as one of nontraditional cardiovascular diseases risk factors, is elevated in all patients with chronic renal failure and it's positive correlation with some other risk factors was found.

Serum levels of nitric oxide and endothelin-1 in patients treated with continuous ambulatory peritoneal dialysis.

End-stage renal disease (ESRD) and its treatment modules affect almost all organs and organ systems including vascular endothelium. It is well known that disturbance of vasoactive substances (nitric oxide - NO and endothelin-1 - ET-1) production appears in these patients. There is a small number of studies which investigated serum levels of NO and ET-1 in ESRD patients treated with continuous ambulatory peritoneal dialysis (CAPD). Therefore our study aimed to measure serum levels of NO and ET-1 in this population. This study included 23 ESRD patients (10 males and 13 females) treated with CAPD, mean age 55.8 ± 15.8 years. Mean duration of CAPD treatment in this group of patients was 3.4 ± 14.7 years. Besides this group of patients (CAPD), we included a second group which consisted of 30 healthy controls [14 males, 16 females, mean age 51.8 (±15.6) years]. Our results show significantly higher serum levels of NO in CAPD patients x ± SD = 19.09 ± 6.9) in comparison to the control group (x ± SD = 9.5 ± 1.9) (p < 0.05). There was no significant difference in serum levels of ET-1 between CAPD patients x ± SD = 7.3 ± 5.6) and the control group (x ± SD = 6.6 ± 4.2), (p > 0.05). From our results, we concluded that imbalance in production of vasoactive substances is present in CAPD patients. This imbalance can lead to disturbance in local blood flow control. These pathophysiological mechanisms can cause significant hemodynamic disturbance (hypertension) and atherosclerosis.

[Assessment of recombinant human thyrotropin application in following-up patients with well-differentiated thyroid carcinoma].

BACKGROUND/AIM: The most sensitive indicators for detecting recurrence of well-differentiated thyroid cancer (DTC) are 131I whole body scintigraphy (WBS) and measurement of serum thyroglobulin (Tg). In order to perform it, it is necessary to raise the level of endogenous tiroid-stimulating hormon (TSH), which can be achieved by L-thyroxine withdrawal for 3-5 weeks or administration of recombinant human thyrotropin (rhTSH) without requiring the discontinuation of thyroid hormone therapy. The aim of this study was to assess the effect of rhTSH using in comparison to the traditional thyroid hormone withdrawal in the follow-up of patients with DTC. METHODS: This retrospective study included 44 patients, mean age 48.8 years, with DTC divided into 2 groups. The group I consisted of patients (n = 31) in which the analysis in the follow-up (WBS with 131I, TSH, Tg and antiTgAt) made in the hypothyroid state, and group II patients (n = 13) in which they made after the administration of rhTSH. The presence of 13 symptoms and signs of hypothyroidism was investigated on the day of giving 131I. Quality of life was evaluated using a modified form: the quality of life scale (SF-36) completed on the day of giving 131I. RESULTS: In both groups, serum TSH reached a very good stimulation level, but significantly higher in the group II (group I 30.3-101.5 microlU/mL, group II 68.6-192.0 microlU/mL, p < 0.05). In both groups, TSH-stimulated Tg was higher (group I 0.1-546.0 ng/mL, group II 0.1-7517 ng/mL) comapred to value during the L-thyroxine therapy (group I 0.1-495.0 ng/mL, group II 0.1-2785 ng/mL). There was no difference in technical quality of WBS obtained from both groups. The patients in the group I had attended 8-13 symptoms of hypothyroidism, while patients in group II did not have symptoms of hypothyroidism. The patients after application of rhTSH, showed statistically significantly better quality of life as compared with those who showed to have L-thyroxine withdrawal, (74-91 points vs 43-62 points; p < 0.05). The rhTSH was well tolerated, with nausea occurring in only one patient. CONCLUSION: Administration of rhTSH in the follow-up of patients with DTC prevents the debilitating effects of hypothyroidism contributing to the maintenance of metabolic homeostasis of the organism and preserves the quality of life. RhTSH is safe, effective and easy to use, but is still an expensive product in our country.

Changes in spirometry over time in uremic patients receiving long-term hemodialysis therapy.

Complications of respiratory system in patients suffering from chronic renal failure who are treated with regular haemodialysis are well known. However, the influence of the duration of haemodialysis on pulmonary function is less understood. The aim of this study was to determine spirometry changes in patients on chronic haemodialysis over a five-year period. We tested 21 patients, out of which 11 female and 10 male, mean age of 50 (+/- 11) years. The mean duration of haemodialysis was 52.2 (+/- 44.7) months at the time of the inclusion. We performed spirometry testings in all patients, one hour before start and one hour after completion of haemodialysis. All parameters of spirometry recorded one hour after completion of haemodialysis (FVC, FEV1, FEF75, 50, 25, % of predicted), improved significantly (p < 0.01). After five years, only FVC demonstrated significant decline and none of the recorded spirometry parameters improved significantly one hour post haemodialysis compared to pre-haemodialysis period. Analysis of post-dialysis parameters of spirometry at the study onset and following five years of haemodialysis showed that all parameters, except FEF50 (p > 0.05), significantly deteriorated (p < 0.01). Patients who are on long-term haemodialysis show a significant decline in FVC following five years of treatment. Although the spirometry changes in observed population treated with chronic haemodialysis have reversible character during the first years of renal replacement therapy, five years after these changes become irreversible.

Detection of pulmonary calcification in haemodialised patients by whole-body scintigraphy and the impact of the calcification to parameters of spirometry.

The early diagnosis of metastatic pulmonary calcification is beneficial, as some patients may develop restrictive changes in respiratory function or in some cases lethal acute respiratory distress. The aim of the study was to evaluate whether scanning with 99(m)Tc DPD might be useful in early diagnosis of pulmonary calcification in setting of chronic renal failure and hemodialysis and if presence of pulmonary calcification is associated with an abnormality in respiratory parameters. Forty-two patients with end-stage renal disease, who were treated by regular haemodialysis, were investigated. Twenty five (59.5%) out of forty two patients had increased lung uptake of 99(m)Tc DPD at whole body scintigraphy-grade 2 group. These patients were on dialysis 149±26 months compared with 57±16 months in 17 patients with a normal lung uptake of 99(m)Tc DPD at whole body scintigraphy- grade 1 group (p<0.01). In grade 2 group 22 patients (88%) had significantly lower (p<0.01) parameters of spirometry (FEF25-75, FEF75 FEF50, FEF25) compared to predicted values while in grade 1 group the parameters were significantly lower in only six patients (35.3%). There was statistically insignificant difference between these two groups regarding parathyroid hormone level (p>0.05). These observations confirm previous findings that scintigraphy with 99(m)Tc DPD may be efficious in early diagnosis of pulmonary calcification in hemodialised patients as well as the fact that spirometry is useful in patients with confirmed pulmonary calcifications.

99m Tc-sestamibi scintimammography in detection of recurrent breast cancer.

The aim of this study was to asses the accuracy of 99mTc-sestamibi scintimammography in patients with suspected recurrent breast cancer in the breast or loco regional tissues. After routine analyses in twenty-eight women (clinical examination, ultrasound, X-ray mammography, and fine needle aspiration biopsy) they were examined by scintimammography. All patients with suspected recurrent cancer in the breast or loco regional tissues (19) undergone surgery and the final diagnosis was determined by histopathological examination. Another 9 patients were followed 6-24 months. The scintigraphic studies were correlated with radiological findings and/or with histopathology. There were 19 patients with recurrent tumours (15 with loco-regional recurrent and 4 in another breast). X-ray mammography identified 13 of these cancers. 99mTc-sestamibi scintimammography identified seventeen of recurrent breast cancers. In the seven out of nine patients without cancer, scintimammography were reported as having no changes consistent with cancer. X-ray mammography showed suspected cancer lesions in four out of nine patients without cancer. There were two false-positive scintimammograms and one false negative. Axillary lymph node recurrence occurred in four patients. All of them were positive on scintimammography. 99mTc-sestamibi scintimammography showed higher sensitivity, specificity and accuracy per patient than did X-ray mammography (90,9% vs. 63,6%, 71,4% vs. 57,1% and 83,3% vs. 61,1%, respectively). To identifying recurrent breast cancer disease is better to use scintimammography than X-ray mammography.

[The assessment of anaerobic capacity in athletes of various sports].

INTRODUCTION: The present study deals with anaerobic power capacity in athletes, differences between power capabilities of these athletes in relation to the type of sports and differences in regard to nonathletes. The goal of this study was to analyze parameters of anaerobic capacity and also to examine if the type and duration of the training period affect values of anaerobic capacity. MATERIAL AND METHODS: This study included 95 male subjects: non-athletes and athletes of various sports: judo players, rowers and soccer players. Anaerobic capacity was determined using the Wingate test. RESULTS AND DISCUSSION: The obtained results show a statistically higher anaerobic capacity in judo players (PP 798 W - 9.64 W/kg) in regard to soccer players (PP 763 W - 9.75 W/kg), rowers (PP 691 W - 8.8 4 W/kg) and non-athletes (PP 557 W - 6.93 W/kg). Judo is a sport which requires high anaerobic capacity. Our results show that athletes have a higher anaerobic power capacity in regard to non-athletes. It can be explained solely by physical training. athletes

Ventilator function improvement in patients undergoing regular hemodialysis: relation to sex differences.

Uremic lung is different entity then oedema present in cardiovascular diseases or in adult respiratory distress syndrome as well. This state is one of the possible complications in patients with chronic renal failure (CRF) receiving regular hemodialysis (HD). There are several studies suggesting that in these patients in 30-40% cases pulmonary hypertension was developed. It is known that patients with primary pulmonary hypertension have peripheral airway obstruction The data also showed that primary as well secondary pulmonary hypertension are more often developed in females; even real reason is still unknown. The aim of the study was to estimate the ventilator function improvement in patients with CRF receiving regular HD related to sex differences. The study population consisted in 39 patients with CRF, with no cardiac and pulmonary diseases. These patients were treated by regular hemodialysis using bicarbonate or acetate mode, respectively. They were divided into two groups according to the sex. Spirometry parameters before and after onset of hemodialysis were recorded. The results were analyzed using Student t-test and presented as mean +/-SD. All p values <0,05 were considered significant. The result showed that ventilatory function in male patients is significantly improved, especially VC and FEV1, whereas in female patients improvement had not statistical significance. It can be concluded that one of the possible reasons for slight improvement of ventilator function in female patients is pulmonary hypertension.