The GRP94 Inhibitor PU-WS13 Decreases M2-like Macrophages in Murine TNBC Tumors: A Pharmaco-Imaging Study with 99mTc-Tilmanocept SPECT.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancers and is not eligible for hormone and anti-HER2 therapies. Identifying therapeutic targets and associated biomarkers in TNBC is a clinical challenge to improve patients' outcome and management. High infiltration of CD206+ M2-like macrophages in the tumor microenvironment (TME) indicates poor prognosis and survival in TNBC patients. As we previously showed that membrane expression of GRP94, an endoplasmic reticulum chaperone, was associated with the anti-inflammatory profile of human PBMC-derived M2 macrophages, we hypothesized that intra-tumoral CD206+ M2 macrophages expressing GRP94 may represent innovative targets in TNBC for theranostic purposes. We demonstrate in a preclinical model of 4T1 breast tumor-bearing BALB/c mice that (i) CD206-expressing M2-like macrophages in the TME of TNBC can be specifically detected and quantified using in vivo SPECT imaging with 99mTc-Tilmanocept, and (ii) the inhibition of GRP94 with the chemical inhibitor PU-WS13 induces a decrease in CD206-expressing M2-like macrophages in TME. This result correlated with reduced tumor growth and collagen content, as well as an increase in CD8+ cells in the TME. 99mTc-Tilmanocept SPECT imaging might represent an innovative non-invasive strategy to quantify CD206+ tumor-associated macrophages as a biomarker of anti-GRP94 therapy efficacy and TNBC tumor aggressiveness.

Postoperative renal functional changes assessed by 99mTc-DTPA scintigraphy and predictive factors after miniaturized percutaneous nephrolithotomy and retrograde intrarenal surgery: An observational 1-year follow-up study.

Purpose: We evaluated the comparative effect of miniaturized percutaneous nephrolithotomy (mini-PCNL) and retrograde intrarenal surgery (RIRS) on perioperative kidney function by use of diethylenetriamine penta-acetic acid (99mTc-DTPA) scintigraphy and identified significant predictors associated with deterioration or amelioration of renal function after surgery. Materials and Methods: All 70 patients who underwent mini-PCNL or RIRS between 2012 and 2016 were monitored by 99mTc-DTPA scintigraphy preoperatively. Patients with abnormal renal function were monitored from 3 to 12 months postoperatively. Logistic regression analyses were conducted to estimate the predictors of aggravated renal dysfunction and improvement. Results: The difference in preoperative renal function between the contralateral and the operative side was >10% in 57 patients (81.4%). Among those in the group with abnormal renal function, 40 (70.2%), 10 (17.5%), and 7 (12.3%) patients showed stability, deterioration, and improvement in renal function at postoperative year 1, respectively. Functional changes did not differ according to the type of surgery. A high level of serum creatinine preoperatively (p=0.060) and a history of previous stone procedures (p=0.051) showed borderline significance for prediction of deterioration in renal function. Conclusions: RIRS and mini-PCNL had similar effects and favorable outcomes on renal function during a 1-year follow-up period. High baseline serum creatinine levels and a history of procedures warrant careful attention.

99mTc-DTPA SPECT/CT provided guide on triamcinolone therapy in Graves' ophthalmopathy patients.

INTRODUCTION: Distinguishing between the active and inactive stages of Graves' ophthalmopathy (GO) is essential for making treatment decisions. 99mTc-DTPA SPECT/CT is sensitive in identifying inflammation in extraocular muscles of GO patients, which we designate 99mTc-DTPA-active. This study aimed to evaluate the response of 99mTc-DTPA-active GO patients to local immunosuppressive therapy. MATERIALS AND METHODS: Sixty-four 99mTc-DTPA-active GO patients (89 eyes) were retrospectively analyzed. Forty-five patients (64 eyes) received repeated peribulbar triamcinolone injection, and 19 patients (25 eyes) received no immunosuppressive treatment. Ophthalmological assessment, including clinical activity score, eyelid retraction, eyelid aperture, proptosis, diplopia, and ocular mobility, was recorded before and after treatment. RESULTS: Compared with untreated patients, the clinical activity score decreased significantly (P < 0.001) while eye symptoms (soft-tissue swelling and eyelid retraction and aperture) improved significantly (P = 0.02, P < 0.001, P < 0.001, respectively) in treated patients after six months. The inferior and medial recti were significantly smaller (P < 0.001, P < 0.001, respectively), and 99mTc-DTPA uptake in the two recti was significantly less (P = 0.001, P = 0.01, respectively) in treated patients than in untreated patients after 3 months. CONCLUSION: Clinical activity score of < 3 does not indicate inactive GO, as revealed with 99mTc-DTPA SPECT/CT. Patients with 99mTc-DTPA-active GO can improve the symptoms with peribulbar triamcinolone injection.

A comparison between 2017 FAS and 2012 CKD-EPI equations: a multi-center validation study in Chinese adult population.

BACKGROUND: The recent guidelines recommend using the estimated glomerular filtration rate (eGFR) to evaluate renal function. There are two reported full-age-spectrum (FAS) equations in 2017, which are based on serum cystatin C concentrations with or without accompanying serum creatinine level (FASCr-Cys or FASCys). We compared the performance and assessed the applicability of the new FAS equation with the 2012 CKD-EPI (CKD-EPICys and CKD-EPICr-Cys) equation in Chinese subjects. METHODS: A total of 1184 patients, mean aged 55.06 year who underwent 99mTc-DTPA GFR measurements (rGFR) from four hospitals were enrolled. The bias (eGFR-rGFR), precision (interquartile range of difference [IQR]), and accuracy (the proportion of eGFR within 30% of rGFR [P30]) of eGFR and rGFR calculated by four equations were compared. RESULTS: Generally, the equation based on the combination of Cys and Scr performed superior to that on the basis of Cys alone, either the CKD-EPICr-Cys or the FASCr-Cys. Detailedly, referred to rGFR (67.33 ml/min/1.73 m2), the CKD-EPICys, CKD-EPICr-Cys, FASCys, and the FASCr-Cys estimated GFR 56.46 ml/min/1.73 m2, 62.79 ml/min/1.73 m2, 56.45 ml/min/1.73 m2, and 61.04 ml/min/1.73 m2, gave ROCAUC0.944, 0.954, 0.943, and 0.953, respectively. Another comparison as to bias, precision, P30, and RMSE with FASCr-Cys were - 2.87 ml/min/1.73 m2, 19.01 ml/min/1.73 m2, 74.16%, and 17.84 ml/min/1.73 m2 showed that FASCr-Cys performed approximately more accurate than other equations, as well as the diagnostic consistency of GFR staging. In the rGFR < 60 ml/min/1.73 m2 subgroup, the FASCr-Cys equation showed the best performance. In older subjects, compared with FASCys, CKD-EPICr-Cys, and CKD-EPICys, the FASCr-Cys equation had relatively less bias (- 8.09 vs. - 9.63, - 7.52, - 11.04, P < 0.05), most precise (15.18 vs. 16.32, 15.22, 16.63), and most accuracy, P30 was statistically different from the other equations, and achieved a ideal value > 70%. CONCLUSION: The performance of the FASCr-Cys equation is better than that of the CKD-EPICr-Cys equation in the Chinese population, particularly in the elderly. Yet, further modification of FAS equations from a large-scale study could be more suitable for the Chinese population, particularly in older people.

The new Asian modified CKD-EPI equation leads to more accurate GFR estimation in Chinese patients with CKD.

OBJECTIVE: To verify whether the new Asian modified CKD-EPI equation improved the performance of original one in determining GFR in Chinese patients with CKD. METHOD: A well-designed paired cohort was set up. Measured GFR (mGFR) was the result of 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) dual plasma sample clearance method. The estimated GFR (eGFR) was the result of the CKD-EPI equation (eGFR1) and the new Asian modified CKD-EPI equation (eGFR2). The comparisons were performed to evaluate the superiority of the eGFR2 in bias, accuracy, precision, concordance correlation coefficient and the slope of regression equation and measure agreement. RESULTS: A total of 195 patients were enrolled and analyzed. The new Asian modified CKD-EPI equation improved the performance of the original one in bias and accuracy. However, nearly identical performance was observed in the respect of precision, concordance correlation coefficient, slope of eGFR against mGFR and 95 % limit of agreement. In the subgroup of GFR < 60 mL min-1/1.73 m2, the bias of eGFR1 was less than eGFR2 but they have comparable precision and accuracy. In the subgroup of GFR > 60 mL min-1/1.73 m2, eGFR2 performed better than eGFR1 in terms of bias and accuracy. CONCLUSION: The new Asian modified CKD-EPI equation can lead to more accurate GFR estimation in Chinese patients with CKD in general practice, especially in the higher GFR group.

Laser stimulation of the acupoint 'Zusanli' (ST.36) on the radiopharmaceutical biodistribution in Wistar rats.

Laser used to stimulate acupoints is called laser acupuncture (LA). It is generally believed that similar clinical responses to manual acupuncture can be achieved. Here we analysed the effects of the laser (904 nm) at the 'Zusanli' acupoint (ST.36) of the stomach meridian on the biodistribution of the radiopharmaceutical Na(99m)TcO4. Wistar rats were divided into control (CG) and experimental groups (EG). The EG were exposed daily to the laser (904 nm) at ST.36 with 1 joule/min (40 mW/cm(2)) for 1 min. The animals of the CG were not exposed to laser at all. On the 8th day after LA, the animals were sedated and Na(99m)TcO4 was administered. After 10 min, the animals were all sacrificed and the organs removed. The radioactivity was counted in each organ to calculate the percentage of radioactivity of the injected dose per gram (%ATI/ g). Comparison of the %ATI/g in EG and CG was performed by Mann-Whitney test. The %ATI/g was significantly increased in the thyroid due to the stimulation of the ST.36 by laser. It is possible to conclude that the stimulation of ST.36 does lead to biological phenomena that interfere with the metabolism of the thyroid.

Three-Dimensional Quantitative Evaluation of the Segmental Functional Reserve in the Cirrhotic Liver Using Multi-Modality Imaging.

To quantitatively evaluate the regional functional reserve in the cirrhotic liver and to seek related index that reflects diminished segmental liver function. A 3D system for quantitative evaluation of the liver was used to fuse technetium-99m galactosyl human serum albumin single-photon emission computed tomography and computed tomography images from 20 patients with cirrhotic liver and hepatocellular carcinoma. A set of parameters reflecting liver function including morphological liver volume, functional liver volume, functional liver density (FLD), and the drug absorption rate constant for hepatic cells (GSA-K) was calculated. Differences in FLD and GSA-K in intrahepatic segments were compared in patients with a tumor embolus (Group Y) and those without such an embolus (Group N) in the right portal vein. Differences in FLD and GSA-K in tumor-bearing (T+ group) and tumor-free (T- group) segments in patients with no tumor embolus (Group N) were also compared. Eleven living donor liver transplantation donor served as the control group. The FLD of the liver as a whole was significantly lower in patients with cirrhosis than in the control group (0.53 ±â€Š0.13 vs 0.68 ±â€Š0.10, P = 0.010). The FLD in segments of the right hemiliver was significantly lower than that in segments of the left hemiliver in Group Y (0.31 ±â€Š0.21 vs 0.58 ±â€Š0.12, P = 0.002) but not in Group N (0.60 ±â€Š0.19 vs 0.55 ±â€Š0.13, P = 0.294). FLD was 0.45 ±â€Š0.17 in the T+ group and 0.60 ±â€Š0.08 in the T- group (P = 0.008). Differences in GSA-K in intrahepatic segments were not significant. In the control group, differences in FLD and GSA-K in intrahepatic segments were not significant. The segmental liver functional reserve can be quantitatively calculated. FLD, but not GSA-K, is an index that reflects diminished regional liver function caused by portal flow obstruction or tumor compression.

Comparison of intraosseous and peripheral venous fluid dynamics in the desert tortoise (Gopherus agassizii).

The efficacy of intraosseous catheterization has not been described previously in the desert tortoise (Gopherus agassizii). The goal of this study was to describe and compare the efficacy of four intraosseous catheter sites (humerus, femur, plastocarapacial junction [bridge], and gular region of the plastron) to jugular catheterization. Five adult tortoises were catheterized in each of the sites at least once. The distribution of a bolus injection of radiopharmaceutical (technetium-99m-diethylenetriaminepentaacidic acid [99mTc -DTPA]) was monitored via gamma camera over 2-min periods at five time intervals over 24 min. Compared to jugular catheterization, the humerus and femur sites provided the next best vascular access, with 84.4 and 61.8% of activity reaching the systemic circulation by 7 min, respectively. The bridge and gular catheter sites were less effective with only 41.9 and 40.8% systemic activity, respectively. Intraosseous catheters were no more technically difficult to place than jugular catheters and were less commonly dislodged, making them a viable option for vascular access in tortoises.

Tc-99m diethylenetriamine pentaacetic acid (DTPA) renal function reserve estimation: is it a reliable predictive tool for assessment of preclinical renal involvement in scleroderma patients?

Prognosis of systemic sclerosis (SSc) depends on internal organ involvement. We assessed the value of renal function reserve (RFR) for the detection of preclinical nephropathy in scleroderma. Thirty SSc patients with normal serum creatinine and 30 healthy controls were included. Medsger disease severity score, glomerular filtration rate (GFR), and microalbuminuria were measured. Tc-99m DTPA was utilized for GFR measurement at baseline and after oral protein overload (stimulated GFR). RFR was calculated as the percentile increase of stimulated GFR. SSc patients had lower means of baseline GFR (P=0.001), stimulated GFR (P=0.004), RFR (P=0.046), and higher microalbuminuria (P=0.009) than controls. According to baseline GFR, SSc patients showed three categories-normal baseline GFR (n=12), hyperfiltration GFR (n=3), and reduced baseline GFR (n=15). In the former category, RFR was normal in 6/12 patients and abnormal in the remainders (50%). Hyperfiltration patients and those with reduced baseline GFR showed abnormal RFR. A statistically significant negative association was found between microalbuminuria versus stimulated GFR and RFR (r= -0.5, P=0.007 and r= -0.45, P=0.013, respectively). The majority of SSc patients with abnormal RFR had disease duration of ≥48 months (60% vs. 20%, P=0.008). All SSc patients with pulmonary hypertension had abnormal RFR, while reduced baseline GFR was noted in only 60%. A significant negative correlation was found between reduced baseline GFR and cumulative dose of corticosteroids in SSc patients (r= -0.4, P=0.022). RFR estimation could be a useful predictive marker for preclinical renal involvement in SSc patients so that early prophylactic measures and therapy modifications could be considered.

Decorporation and therapeutic efficacy of liposomal-DTPA against thorium-induced toxicity in the Wistar rat.

PURPOSE: This study examined the effect of liposomal encapsulation of (99m)Tc-labeled diethylenetriaminepentaacetic acid (metastable technetium labeled DTPA) on its organ distribution and therapeutic effect of optimized neutral liposomal-DTPA against thorium ((232)Th)-induced liver toxicity and its accumulation in rat animal model. MATERIALS AND METHODS: (99m)Tc-DTPA was encapsulated in neutral (dipalmitoylphosphatidylcholine:cholesterol) and positively (dipalmitoylphosphatidylcholine:cholesterol:stearylamine) charged liposomes using thin film hydration method. Comparative efficacy of liposomal and free DTPA (11.2 mg/kg) was examined in terms of its effect on (232)Th accumulation and subsequent toxicity in the liver and blood of rat administered with (232)Th-nitrate (600 µg/kg). Organ distribution of free or liposomal (99m)Tc-DTPA was determined by solid scintillation counting and (232)Th accumulation by Inductively Coupled Plasma-Atomic Emission Spectroscopy. RESULTS: Neutral liposomes encapsulated with (99m)Tc-DTPA showed more uptake in liver, spleen and blood than with positively charged liposomal- and free- (99m)Tc-DTPA. Administration of (232)Th-nitrate to rat significantly increased the levels of liver toxicity markers and of oxidative injury, which were found to be restored more significantly by neutral liposomal-DTPA than free-DTPA. The accumulation of (232)Th in liver and blood of contaminated mice was found to be decreased more significantly by neutral liposomal-DTPA than by free-DTPA. CONCLUSIONS: Decorporation and consequent mitigation of (232)Th induced toxicity may be significantly improved by liposomal encapsulation of DTPA, a chelating agent.

Evaluating the effects of 14-day oral vedaprofen and tolfenamic acid treatment on renal function, hematological and biochemical profiles in healthy cats.

The objective of this study was to evaluate the effects of the nonsteroidal anti-inflammatory drugs vedaprofen and tolfenamic acid on renal function after oral administration for 2 weeks in healthy cats. Experiments were performed using nineteen domestic short-haired cats randomly divided into one control (n=6) and two treatment groups. All cats in the first (n=6) and second treatment groups (n=7) received vedaprofen (0.5 mg/kg/day) and tolfenamic acid (4 mg/kg/day), respectively. During the experiment, renal function was evaluated using percent renal uptakes of (99m)Technetium-diethylenetriamine-pentaacetic acid ((99m)Tc-DTPA) collected from renal scintigraphy and blood samples used to determine complete blood count and biochemical profiles. Renal scintigraphy and blood collections were performed at days 0, 5, 11, 15, and 45. The percent of renal uptake after the administration of vedaprofen and tolfenamic acid were not significantly different compared to pretreatment (day 0) and control group levels. In addition, significant changes were not observed in hematological and biochemical profiles within or between groups, with the exception of slightly lower numbers in red blood cell counts compared to the normal value on day 45 in the tolfenamic acid-treated group. Taken together, we conclude 14-day administration of vedaprofen and tolfenamic acid might not cause any adverse effects on renal function, hematological and serum biochemical variables.

Sucralose sweetener in vivo effects on blood constituents radiolabeling, red blood cell morphology and radiopharmaceutical biodistribution in rats.

Effects of sucralose sweetener on blood constituents labelled with technetium-99m ((99m)Tc) on red blood cell (RBC) morphology, sodium pertechnetate (Na(99m)TcO(4)) and diethylenetriaminepentaacetic acid labeled with (99m)Tc ((99m)Tc-DTPA) biodistribution in rats were evaluated. Radiolabeling on blood constituents from Wistar rats was undertaken for determining the activity percentage (%ATI) on blood constituents. RBC morphology was also evaluated. Na(99m)TcO(4) and (99m)Tc-DTPA biodistribution was used to determine %ATI/g in organs. There was no alteration on RBC blood constituents and morphology %ATI. Sucralose sweetener was capable of altering %ATI/g of the radiopharmaceuticals in different organs. These findings are associated to the sucralose sweetener in specific organs.

Cisplatin nephrotoxicity aggravated by cardiovascular disease and diabetes in lung cancer patients.

Ageing lung cancer patients may be at increased risk of Cisplatin (Cp) nephrotoxicity, because of comorbidities leading to accelerated ageing of the kidneys. Therefore, the Cp-induced impairement of renal function was compared between no comorbidity (NC) and hypertension plus ischaemic heart disease (CD) patients or others having diabetes mellitus plus ischaemic heart disease (DMIH). In a preliminary study, glomerular filtration rate (GFR) was measured by clearance of technetium 99m-labelled diethylene-thiamine penta-acetate in 38 lung cancer patients with normal serum creatinine concentration ([creat]). Then, the incidence of nephrotoxicity was analysed retrospectively over 1st-4th cycles of Cp treatment among 242 lung cancer patients with initially normal [creat]. GFR was repeatedly estimated using calculated creatinine clearance. Pre-treatment GFR was 57 ± 3 mL·min⁻¹·m⁻² in those with normal (n = 15) and 42 ± 2 mL·min⁻¹·m⁻² in those with pathologically increased (n = 23) [creat] any time following their 2nd-4th Cp cycle (p < 0.05). The retrospective analysis revealed that Cp-induced nephrotoxicity developed in 7.5% of the NC (n = 80), in 20.9% of the CD (n = 110) and in 30.8% of the DMIH (n = 52) subgroups. Within the overall dropout rate from further Cp chemotherapy, nephrotoxicity was responsible in 14% of NC, 38% in CD and 75% in DMIH patients. A major portion of our ageing lung cancer patients suffered from comorbidities leading to reduced renal resistance to Cp nephrotoxicity.

Increased epithelial permeability in pulmonary fibrosis in relation to disease progression.

Epithelial injury contributes to pathogenesis in idiopathic pulmonary fibrosis (IPF) but its role in the interstitial lung disease (ILD) of systemic sclerosis (SSc) is uncertain. We quantified the prognostic significance of inhaled technetium-99m ((99m)Tc)-labelled diethylene triamine pentacetate (DTPA) pulmonary clearance, a marker of the extent of epithelial injury, in both diseases. Baseline (99m)Tc-DTPA pulmonary clearance was evaluated retrospectively in patients with SSc-ILD (n = 168) and IPF (n = 97) against mortality and disease progression. In SSc-ILD, the rapidity of total clearance (hazard ratio (HR) 1.02, 95% CI 1.01-1.03; p = 0.001) and the presence of abnormally rapid clearance (HR 2.10; 95% CI 1.25-3.53; p = 0.005) predicted a shorter time to forced vital capcity (FVC) decline, independent of disease severity. These associations were robust in both mild and severe disease. By contrast, in IPF, delayed clearance of the slow component, an expected consequence of honeycomb change, was an independent predictor of a shorter time to FVC decline (HR 1.01, 95% CI 1.00-1.02; p<0.01). Epithelial injury should be incorporated in pathogenetic models in SSc-ILD. By contrast, outcome is not linked to the overall extent of epithelial injury in IPF, apart from abnormalities ascribable to honeycombing, suggesting that core pathogenetic events may be more spatially focal in that disease.

Early chemotherapy response evaluation in tumors by 99mTc-DTPA-DG.

PURPOSE: The aim of this study was to evaluate the utility of 99mTc-diethylenetriaminepentaacetic acid-deoxyglucose (DTPA-DG) for monitoring the early response of tumors to chemotherapy. METHOD: To evaluate the role of 99mTc-DTPA-DG in vitro chemotherapy, the uptake ratios assays were conducted using A549 lung cancer and MCF-7 breast cancer cells after the 2 tumor cell types had been treated with cisplatin and paclitaxel chemotherapeutic agents, respectively. Apoptosis in the 2 cell types, an indicator of chemotherapeutic action, was assessed by inverted fluorescence microscope and flow cytometry. The assessment of 99mTc-DTPA-DG in vivo was performed by scintigraphic imaging studies of 99mTc-DTPA-DG in MCF-7 mammary tumor cell xenografts at timed intervals after treatment. The animals were randomly assigned to 5 groups: group A, saline injection; group B, low-dose cisplatin; group C, high-dose cisplatin; group D, low-dose combination chemotherapy; and group E, high-dose combination chemotherapy. Imaging findings were correlated with the effectiveness of chemotherapy. RESULTS: The uptake rates of 99mTc-DTPA-DG by A549 lung cancer cells and MCF-7 breast cancer cells in the chemotherapeutic groups were all significantly lower than those in the controls (p < 0.01). The apoptotic ratios in the control groups were significantly lower than the apoptotic ratios in the chemotherapeutic treatment groups in the 2 tumor cell types. The uptake ratios and the apoptosis ratios are inverse correlation, which suggested that we could evaluate the chemotherapy response by the uptake of 99mTc-DTPA-DG in vitro. Scintigraphy in MCF-7 mammary tumor xenografts mice demonstrated that tumor could be clearly visualized by 99mTc-DTPA-DG. The efficacy of combined chemotherapy treatment in this xenograft model was assessed by scintigraphy of tumor/muscle ratios. CONCLUSIONS: 99mTc-DTPA-DG is a targeted molecular imaging agent, promising in the evaluation of early response of tumors to chemotherapy.

Chronic kidney disease stage in renal transplantation classification using cystatin C and creatinine-based equations.

BACKGROUND: Current clinical guidelines recommend that renal transplant recipients (RTRs) be classified into chronic kidney disease (CKD) stage using a creatinine-based estimate of glomerular filtration rate (GFR). However, creatinine-based equations are inaccurate in RTRs leading to frequent CKD stage misclassification. It is not known whether the classification of CKD stage would be improved using a cystatin C-based estimate of GFR. METHODS: We measured (99m)Tc-DTPA GFR, cystatin C and creatinine in 198 stable RTRs. GFR was estimated using cystatin C-based equations (Filler, Le Bricon and Rule) and four creatinine-based equations. We determined the proportion, overall and by CKD stage, that were classified correctly by each equation as compared to the (99m)Tc-DTPA GFR. RESULTS: The Filler equation correctly classified 76% of patients compared to only 65% with the abbreviated modification of diet in renal disease (MDRD) equation and 69% with the Cockcroft-Gault equation. In CKD stages two and four, the Filler equation correctly classified 77% and 60% of patients whereas the abbreviated MDRD equation correctly classified 46% and 93% of patients. The area under the curve by receiver operating curve analysis for overall stage classification was uniformly poor for all equations (0.52-0.56). CONCLUSIONS: The cystatin C-based Filler and Le Bricon GFR estimates classified slightly more patients into the correct CKD stage than the standard creatinine-based equations in stable RTRs although the overall diagnostic accuracies were similar. The differences are modest and prospective studies will be needed to determine if the adoption of these equations for classification would lead to improved recognition of CKD complications or patient care.

Healthy passive cigarette smokers have increased pulmonary alveolar permeability.

QUESTION: Does passive smoking have a measurable effect on lung function in otherwise healthy subjects? There is current interest concerning passive smoking but no objective evidence showing that it has any impact on lung function. METHODS: The pulmonary clearance rate of (99m)Tc-DTPA was measured in 21 healthy volunteers after inhalation as a radio-aerosol and compared between healthy cigarette smokers, passive smokers and non-smokers. All volunteers had normal lung function. RESULTS: Clearance half-times in healthy passive smokers (n=5) were longer than in healthy smokers (n=6) but clearly shorter compared with healthy non-smokers (n=10) with respective mean values of 45.2 (SD 8.3), 24.3 (8.6) and 80.3 (20) min. CONCLUSION: Passive smoking has a functional impact on the lung blood/gas barrier.

Evaluation of alveolar clearance by Tc-99m DTPA radioaerosol inhalation scintigraphy in welders.

OBJECTIVES: The welding process produces metal fumes and gases which may affect respiratory health. Technetium-99m diethylenetriaminepentaacetic acid (Tc-99m DTPA) dynamic lung scanning is an easy, noninvasive method to assess disorders of alveolar-capillary barrier permeability secondary to epithelial damage. We aimed to investigate the alveolar clearance by Tc-99m DTPA radioaerosol inhalation scintigraphy in welders, to assess additive effects of exposure to welding fumes and cigarette smoking on clearance rate of alveolar epithelium and to determine the correlation between Tc-99m DTPA aerosol lung scintigraphy and spirometric measurements. METHODS: Nine nonsmoking welders, 9 smoking welders, and a control group of 6 nonsmokers and 6 smokers were accepted to the study. Tc-99m DTPA radioaerosol inhalation scintigraphy was performed in all subjects. Clearance half time (Tl/2) was calculated by placing a monoexponential fit on the curves. Penetration index (PI) was also calculated on the first minute image. Pulmonary function tests of welders and control group were compared. RESULTS: The mean T1/2 values of Tc-99m DTPA of the nonsmoking welders were significantly higher than those of the nonsmoking control group (82.1+/-24.3 min and 48.1+/-9.7 min, respectively; p = 0.003). The mean T1/2 values of Tc-99m DTPA of the smoking welders were higher than those of the smoking control group (53.3+/-24.5 min and 44.5+/-9.7 min, respectively; p = 0.510). PI of the nonsmoking welders was significantly higher than that of the nonsmoking control group (0.46+/-0.38 and 0.39+/-0.46 respectively; p = 0.004). PI of the smoking welders was significantly higher than that of smoking control group (0.43+/-0.38 and 0.37+/-0.45, respectively; p = 0.019). There was a negative correlation between T1/2 value and FEV1% (r = -0.468, p = 0.016), FVC% (r = -0.442, p = 0.024) and FEF25-75% (r = -0.391, p = 0.048) in the welders and control group. No statistically significant differences were found in the values of the standard pulmonary function tests of any of the subjects. CONCLUSIONS: Welding seems to decrease alveolar clearance which causes an increase in the penetration index. This was considered to be due to fibrotic changes and increased number of alveolar macrophages induced by welding fumes.

Evaluation of right and left ventricular function by quantitative blood-pool SPECT (QBS): comparison with conventional methods and quantitative gated SPECT (QGS).

Though quantitative ECG-gated blood-pool SPECT (QBS) has become a popular tool in research settings, more verification is necessary for its utilization in clinical medicine. To evaluate the reliability of the measurements of left and right ventricular functions with QBS, we performed QBS, as well as first-pass pool (FPP) and ECG-gated blood-pool (GBP) studies on planar images in 41 patients and 8 healthy volunteers. Quantitative ECG-gated myocardial perfusion SPECT (QGS) was also performed in 30 of 49 subjects. First, we assessed the reproducibility of the measurements of left and right ventricular ejection fraction (LVEF, RVEF) and left and right ventricular end-diastolic volume (LVEDV, RVEDV) with QBS. Second, LVEF and RVEF obtained from QBS were compared with those from FPP and GBP, respectively. Third, LVEF and LVEDV obtained from QBS were compared with those from QGS, respectively. The intra- and inter-observer reproducibilities were excellent for LVEF, LVEDV, RVEF and RVEDV measured with QBS (r = 0.88 to 0.96, p < 0.01), while the biases in the measurements of RVEF and RVEDV were relatively large. LVEF obtained from QBS correlated significantly with those from FPP and GBP, while RVEF from QBS did not. LVEF and LVEDV obtained from QBS were significantly correlated with those from QGS, but the regression lines were not close to the lines of identity. In conclusion, the measurements of LVEF and LVEDV with QBS have good reproducibility and are useful clinically, while those of RVEF and RVEDV are less useful compared with LVEF and LVEDV. The algorithm of QBS for the measurements of RVEF and RVEDV remains to be improved.

99mTc-DTPA uptake and electrical impedance measurements in verification of in vivo electropermeabilization efficiency in rat muscle.

OBJECTIVE: In vivo electropermeabilization of cell membranes in rat muscle tissue cause a significant decrease of the electrical impedance, in the frequency region of 1-10 kHz. We aimed to study how the 99mTc-DTPA uptake in the electropermeabilized region correlates to the change of admittance Y = 1/absZ, where Z is the measured impedance. METHODS: The electropermeabilization was performed in vivo by applying high-voltage (0.5-2 kV) short (0.1-2 ms) pulses through gold-plated needle electrodes in skeletal muscle. The impedance was measured before and after each electropermeabilization pulse. The uptake of 99mTc-DTPA uptake in the electropermeabilized region was measured after 6 and 24 hours with a gamma camera. RESULTS: The pulse shape (square and exponential), duration, and amplitude of the applied electric field were varied, and electropermeabilization efficiency was evaluated using the various measurement modalities. Good correlations were found (correlation coefficient approximately 0.9) between the 99mTc-DTPA uptake in the electropermeabilized and control "region of interest" the admittance ratio Y (post-treatment)/Y (pretreatment), and charge displacement parameter Q. CONCLUSION: The electrical impedance measurements method can be utilized in clinical settings to verify the efficiency of electropermeabilization applied to chemotherapy and to power RNAi (RNA-interference) and DNA-plasmid transfection in vaccination, immunization, and gene-therapy.