Marcelo Tatit Sapienza

A MULTI-FACTORIAL BIOLOGICAL MODULATION PROTOCOL THAT AMELIORATES ISCHEMIA-REPERFUSION INJURY SIMULTANEOUSLY REDUCES BILESALT TOXICITY IN PORCINE LIVER TRANSPLANTATION FROM NON-HEART BEATING DONORS

Plasma clearance of 51Cr‐EDTA (51Cr‐EDTA‐Cl) is an alternative method to evaluate glomerular filtration rate (GFR). This study aimed to investigate the concordance between 51Cr‐EDTA‐Cl and renal inulin clearance (In‐Cl) in renal transplant recipients as well to determine the repeatability of 51Cr‐EDTA‐Cl in kidney donors. Forty four kidney recipients and 22 kidney donors were enrolled. Simultaneous measurements of 51Cr‐EDTA‐Cl and In‐Cl were performed. A single dose of 3.7MBq of 51Cr‐EDTA was injected and the plasma disappearance curve was created by taking blood samples at 2, 4, 6 and 8 h after injection. Bland and Altman statistical approach was used to quantify the agreement between In‐Cl and 51Cr‐EDTA‐Cl and to determine the better concordance between all possibilities of measure for the 51Cr‐EDTA‐Cl. The mean of In‐Cl was 44.5 ± 17.9 ml/min/1.73 m2. There was a positive correlation between In‐Cl and all possible measurements of 51Cr‐EDTA‐Cl. 51Cr‐EDTA‐Cl with two samples taken at 4 and 8 h or at 4 and 6 h presenting the narrow limits of agreement and a difference (bias) of 2.8 and 2.7 ml/min, respectively. Two plasma sampling for 51Cr‐EDTA‐Cl was a reliable method to measure GFR compared with In‐Cl and comprises a suitable method to be used in kidney transplanted patients.

Effect of Short-term High-Dose Creatine Supplementation on Measured GFR in a Young Man With a Single Kidney

It currently is unknown whether creatine supplementation is safe for people with or at risk of kidney disease. We report on the short-term effects of creatine supplementation on kidney function in a young man with a single kidney and mildly decreased glomerular filtration rate (GFR). A 20-year-old man who had undergone unilateral nephrectomy and presented with mildly decreased GFR without kidney damage underwent a trial with 35 days of creatine supplementation (20 g/d for 5 days followed by 5 g/d for the next 30 days) and had his kidney function monitored. After the intervention, (51)Cr-EDTA clearance (pre, 81.6 mL/min/1.73 m(2); post, 82.0 mL/min/1.73 m(2)), proteinuria (protein excretion: pre, 130 mg/d; post, 120 mg/d), and electrolyte levels were unchanged. Albuminuria, serum urea level, and estimated creatinine clearance were decreased (pre, 4.6 mg/d; post, 2.9 mg/d; pre, 37 mg/d; post, 28 mg/dL; and pre, 88 mL/min/1.73 m(2); post, 71 mL/min/1.73 m(2), respectively), whereas serum creatinine level was slightly increased (pre, 1.03 mg/dL; post, 1.27 mg/dL), falsely suggesting kidney function impairment. This prospective report suggests that short-term creatine supplementation may not affect kidney function in an individual with a single kidney, mild decreased GFR, and ingesting a high-protein diet (ie, 2.8 g/kg/d). This finding has great relevance considering that creatine-induced kidney disease has been a growing concern, even for healthy people.

Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet?

BackgroundThe aim of this study was to determine the effects of creatine supplementation on kidney function in resistance-trained individuals ingesting a high-protein diet.MethodsA randomized, double-blind, placebo-controlled trial was performed. The participants were randomly allocated to receive either creatine (20 g/d for 5 d followed by 5 g/d throughout the trial) or placebo for 12 weeks. All of the participants were engaged in resistance training and consumed a high-protein diet (i.e., ≥ 1.2 g/Kg/d). Subjects were assessed at baseline (Pre) and after 12 weeks (Post). Glomerular filtration rate was measured by 51Cr-EDTA clearance. Additionally, blood samples and a 24-h urine collection were obtained for other kidney function assessments.ResultsNo significant differences were observed for 51Cr-EDTA clearance throughout the trial (Creatine: Pre 101.42 ± 13.11, Post 108.78 ± 14.41 mL/min/1.73m2; Placebo: Pre 103.29 ± 17.64, Post 106.68 ± 16.05 mL/min/1.73m2; group x time interaction: F = 0.21, p = 0.64). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria remained virtually unchanged.ConclusionsA 12-week creatine supplementation protocol did not affect kidney function in resistance-trained healthy individuals consuming a high-protein diet; thus reinforcing the safety of this dietary supplement.Trial registrationClinicalTrials.gov NCT01817673

Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy

PURPOSE The aim of this study was to evaluate the degree of metastatic bone pain palliation and medullar toxicity associated with samarium-153-EDTMP treatment. METHODS Seventy-three patients with metastatic bone pain having previously undergone therapy with samarium-153-EDTMP (1 mCi/kg) were retrospectively evaluated. Routine follow-up included pain evaluation and blood counts for 2 months after treatment. Pain was evaluated using a subjective scale (from 0 to 10) before and for 8 weeks after the treatment. Blood counts were obtained before treatment and once a week for 2 months during follow-up. Dosimetry, based upon the urinary excretion of the isotope, was estimated in 41 individuals, and the resulting radiation absorbed doses were correlated with hematological data. RESULTS Reduction in pain scores of 75% to 100% was obtained in 36 patients (49%), with a decrease of 50% to 75%, 25% to 50%, and 0% to 25% in, respectively, 20 (27%), 10 (14%), and 7 (10%) patients. There was no significant relationship between the pain response and location of the primary tumor (breast or prostate cancer). Mild to moderate myelosuppression was noted in 75.3% of patients, usually with hematological recovery at 8 weeks. The mean bone marrow dose was 347 +/- 65 cGy, and only a weak correlation was found between absorbed dose and myelosuppression (Pearson coefficient = .4). CONCLUSIONS Samarium-153-EDTMP is a valuable method for metastatic bone pain palliation. A mild to moderate and transitory myelosuppression is the main toxicity observed after samarium therapy, showing a weak correlation with dosimetric measures.

Contrast-enhanced power Doppler imaging: comparison with scintigraphic phases of revascularization of the femoral head in Legg-Calvé-Perthes disease.

The authors evaluated the usefulness of an ultrasound contrast agent (SHU 508A) to help identify different scintigraphic phases of revascularization of the femoral head in children with Legg-Calvé-Perthes (LCP) disease. Eighteen unenhanced and contrast-enhanced power Doppler images and scintigrams of the pathologic hip in 18 children with LCP disease were compared. The scintigraphic stages of Conways classification for LCP disease (stage A, recanalization; stage B, neovascularization) were compared with the degree of vascularity and mean peak enhancement ratios obtained from analysis of Doppler sonograms. Qualitatively, the patients age (≤ or >7 years old) at the time of examination had a significant effect on the degree of vascularity visualized on postcontrast ultrasound images according to the scintigraphic stages. Quantitatively, there were no differences for overall mean peak enhancement ratios between stages A and B. Power Doppler ultrasound increased visualization of Doppler signals significantly but did not help in differentiating scintigraphic phases.

Gallbladder Emptying in Normal Volunteers: Comparative Study Between Cholescintigraphy and Ultrasonography

To assess the reproducibility of and compare the patterns of gallbladder emptying after a fatty meal stimulus, the authors analyzed 10 healthy fasting volunteers (8 men; mean age, 32 years). Cholescintigraphy was obtained after intravenous injection of 185 MBq of Tc-99m DISIDA. A standardized fatty meal was provided 70 minutes after injection. The ejection fraction was measured sequentially by ultrasound and cholescintigraphy 15, 30, 45, and 60 minutes after eating. All patients had repeat studies within 1-3 weeks. The two methods showed a distinct gallbladder time course of emptying after the fatty meal stimulus. Nuclear medicine showed higher values of gallbladder ejection fraction at 45 and 60 minutes after eating when compared to ultrasound (P < 0.01). The plotted curves, using the four different periods of time, also showed different behavior due mainly to distinct angular coefficients (nuclear medicine, 2.6; ultrasound, 0.9). Good reproducibility of fatty meal-induced gallbladder ejection fraction at 30, 45, and 60 minutes was also observed using both methods. Thus, ultrasound and nuclear medicine are reproducible methods of studying gallbladder dynamics. However, nuclear medicine demonstrated continued excretion of bile at 45 and 60 minutes, whereas ultrasound did not show significant volume variations in these time frames.

Correction factors for more accurate estimates of exposure rates near radioactive patients : Experimental, point, and line source models

Radioactive patients may expose others after radiopharmaceutical administrations, and evaluation of the absorbed dose or exposure rates close to patients is important in keeping radiation doses as low as reasonably achievable. Two theoretical exposure models, point source and line source models, are frequently used to calculate exposure or dose rates without the support of actual measurements. If measurements of exposure rates were performed near patients, an experimental exposure model could be implemented. When measurements of exposure rates are performed, these measurements are made inside therapy rooms or other confined places, in which case scattered radiation may significantly influence the measurements. In this study we measured exposure rates from radioactive patients without the influence of scattered radiation and determined correction factors for the theoretical exposure models. The exposure rates from a total of 110 radioactive patients were measured at 1.0 h after oral administration of Na131I for thyroid therapy; the results ±1 SD at distances of 0.5, 1.0, 1.5, 2.0, 3.0, and 4.0 m in front of the patients were (29 ± 6), (9.9 ± 1.7), (4.6 ± 0.9), (2.7 ± 0.5), (1.31 ± 0.25) and (0.74 ± 0.12) × 10−10 C kg−1 MBq−1 h−1 [1.0 × 10−10 C kg−1 MBq−1 h−1 = 14.34 × 10−6 R mCi−1 h−1], respectively. To obtain more accurate estimates of the actual exposure rates from patients using the theoretical exposure models, we found that correction factors should be applied; the functions CFEM = 1.19 + 32.80e−5.92D and CFLS = 0.022Ln(D) + 0.639 describe these correction factors for distances less than or equal to 1.0 m from the patients for experimental and line source exposure models, respectively. The function that describes the correction factors to the point source model is CFPS = 0.224Ln(D) + 0.638 at the same distances; applying these correction factors leads to a reduction from 56% to 1% in the difference between measured exposure rates and theoretical exposure rates calculated by the point source exposure model at a distance of 1.0 m from patients. The results given here provide more accuracy in evaluation of exposure rates and consequently absorbed doses near radioactive patients and allow for more effective radiological protection procedures during patient management.

A new proposal for monitoring patients in nuclear medicine.

The measurement of exposure rates is fundamentally important in the release of patients given radioactive materials and for keeping the exposures of others as low as reasonable achievable. Similar measurement methodologies have generally been used for point and extended sources, but this approach may lead to methodological errors in calculating radiation dose estimates. In this study, nuclear medicine patients who received high activities of Na131I for therapy were monitored using different measurement methodologies, and the results showed that the usual measurement performed at 1.0 m in front of the body resulted in a mean error of 40% between experimental and theoretical exposure rates. The best measurements were obtained when performed at 2.0 m in front of the patients. With this approach, the error was about 2% between experimental and theoretical values. These findings suggest a new methodology for patients’ measurement in nuclear medicine and could be useful for personal monitoring in cases of radiological emergencies involving 131I ingestion.

Tratamento do carcinoma diferenciado da tireóide com iodo-131: intervenções para aumentar a dose absorvida de radiação

OBJECTIVES Our aim was to analyze measures taken to increase the radiation absorbed dose (DOSE) during treatment of well-differentiated thyroid cancer (DTC) with iodine-131. METHODS An increase in DOSE is achieved by: avoiding competition with non-radioactive iodine, stimulating cellular uptake/retention, increasing the administered activity. Basis and results of each one of these methods were reviewed. RESULTS Although it is difficult to demonstrate an increase in survival, there is a direct relation between DOSE and tumoral response in DTC. Different approaches can be used aiming an increase in DOSE, with a possible improvement in tumoral response for treatment with iodine-131. Although DTC is a relatively benign disease, a better response to treatment is highly desirable in high-risk patients, who have few other options of therapy. CONCLUSIONS An increase in DOSE during treatment of DTC can be achieved using the described interventions, which should be used in high-risk cases of DTC.

Efficacy and safety of creatine supplementation in childhood-onset systemic lupus erythematosus: a randomized, double-blind, placebo-controlled, crossover trial

Introduction Creatine supplementation has emerged as a promising non-pharmacological therapeutic strategy to counteract muscle dysfunction and low lean mass in a variety of conditions, including in pediatric and rheumatic diseases. The objective of this study was to examine the efficacy and safety of creatine supplementation in childhood systemic lupus erythematosus (C-SLE). Methods C-SLE patients with mild disease activity (n = 15) received placebo or creatine supplementation in a randomized fashion using a crossover, double-blind, repeated-measures design. The participants were assessed at baseline and after 12 weeks in each arm, interspersed by an eight-week washout period. The primary outcomes were muscle function, as assessed by a battery of tests including one-maximum repetition (1-RM) tests, the timed-up-and-go test, the timed-stands test, and the handgrip test. Secondary outcomes included body composition, biochemical markers of bone remodeling, aerobic conditioning, quality of life, and physical capacity. Possible differences in dietary intake were assessed by three 24-hour dietary recalls. Muscle phosphorylcreatine content was measured through phosphorus magnetic resonance spectroscopy (31 P-MRS). The safety of the intervention was assessed by laboratory parameters, and kidney function was measured by 51Cr-EDTA clearance. Additionally, self-reported adverse events were recorded throughout the trial. Results Intramuscular phosphorylcreatine content was not significantly different between creatine and placebo before or after the intervention (creatine-Pre: 20.5 ± 2.6, Post: 20.4 ± 4.1, placebo-Pre: 19.8 ± 2.0; Post: 20.2 ± 3.2 mmol/kg wet muscle; p = 0.70 for interaction between conditions). In addition, probably as a consequence of the lack of change in intramuscular phosphorylcreatine content, there were no significant changes between placebo and creatine for any muscle function and aerobic conditioning parameters, lean mass, fat mass, bone mass, and quality of life scores (p > 0.05). The 51Cr-EDTA clearance was not altered by creatine supplementation and no side effects were noticed. Conclusion A 12-week creatine supplementation protocol at 0.1 g/kg/d is well tolerated and free of adverse effects but did not affect intramuscular phosphorylcreatine, muscle function, free-fat mass or quality of life in non-active C-SLE patients. Trial registration Clinicaltrials.gov number: NCT01217320.