Intra-individual and inter-individual variation in breath alcohol pharmacokinetics: The effect of short-term variation

Ten male and 8 female students underwent serial breath alcohol concentration (BrAC) measurements on a CAMIC Datamaster on two consecutive occasions, early evening and again the following morning. Subjects were fasted for 6 h before receiving alcohol as white wine (12.5% by volume) at doses of 38–45 g for males and 26–37 g for females, consumed over 10 min. Specific individual doses were calculated individually from height and weight (according to the Forrest Method) to give target C₀ breath alcohol concentrations of 35 μg/100 ml breath in males and 31 μg/100 ml breath in females.BrAC versus time curves were constructed for each subject and the values of peak BrAC (C_max), BrAC extrapolated at zero time (C₀), time taken to reach peak (T_max) and rate of elimination (ß) were recorded directly from the curves. Values of C₀ taken from the BrAC–time curves varied widely, from 21 to 47 μg/100 ml on visit 1 and from 22 to 45 μg/100 ml on visit 2. Widmark Factors calculated from these C₀ values averaged 0.74 (range, 0.59–1.06) in males and 0.73 (range, 0.58–1.05) in females. Elimination rate was higher in the morning than evening in both males (7.4 versus 5.7 μg/100 ml/h) and females (6.9 versus 5.8 μg/100 ml/h). Elimination rates in males and females were not significantly different. Total body water, measured by electronic scales, averaged 58.7% (range, 56.6–63%) in males and 48.3% (range, 40.9–57.6%) in females. Widmark Factors calculated by various established mathematical methods were 0.73–0.77 in males and 0.61–0.64 in females.     

High cardiorespiratory fitness is inversely associated with incidence of overweight in adolescence: A longitudinal study

To assess the association of baseline cardiorespiratory fitness (CRF) with incidence of overweight over a 4.6‐year period in adolescence. In a cohort of 4878 adolescents, we assessed body mass index in years 2001–2003 and 2007. CRF was assessed at baseline as maximal oxygen consumption (VO_2max, mL/kg/min) using the 20‐m shuttle run test and was examined against incidence of overweight at follow‐up. Estimated VO_2max at baseline was higher in males than in females, P < 0.001, and was lower in overweight and obese than in non‐overweight subjects. The incidence of overweight at follow‐up among non‐overweight participants at baseline was 15.5% [95% confidence interval (CI) 13.7% to 17.3%] in males and 5.6% (95% CI 4.9% to 7.0%) in females, P < 0.001. Adjusted odds ratio for incidence of overweight in participants in the fourth quartile of VO_2max was 0.40 (95%CI 0.26 to 0.61) in males and 0.57 (95% CI 0.33 to 0.99) in females in comparison with participants in the first quartiles of VO_2max. Incidence of overweight was three times more frequent in males than in females. Among non‐overweight at baseline, high fitness levels were inversely associated with incidence of overweight at follow‐up, suggesting that interventions aiming to increase CRF in early childhood might help reverse increasing trends in obesity.     

Test‐retest variability of VO2max using total‐capture indirect calorimetry reveals linear relationship of VO2 and Power

This study aimed to analyze the intra‐individual variation in VO_2max of human subjects using total‐capture and free‐flow indirect calorimetry. Twenty‐seven men (27 ± 5 year; VO_2max 49‐79 mL?kg^?1?min^?1) performed two maximal exertion tests (CPETs) on a cycle ergometer, separated by a 7 ± 2 day interval. VO₂ and VCO₂ were assessed using an indirect calorimeter (Omnical) with total capture of exhalation in a free‐flow airstream. Thirteen subjects performed a third maximal exertion test using a breath‐by‐breath calorimeter (Oxycon Pro). On‐site validation was deemed a requirement. For the Omnical, the mean within‐subject CV for VO_2max was 1.2 ± 0.9% (0.0%‐4.4%) and for ergometer workload P _max 1.3 ± 1.3% (0%‐4.6%). VO_2max values with the Oxycon Pro were significantly lower in comparison with Omnical (P < 0.001; t test) with mean 3570 vs 4061 and difference SD 361 mL?min^?1. Validation results for the Omnical with methanol combustion were ?0.05 ± 0.70% (mean ± SD; n = 31) at the 225 mL?min^?1 VO₂ level and ?0.23 ± 0.80% (n = 31) at the 150 mL?min^?1 VCO₂ level. Results using gas infusion were 0.04 ± 0.75% (n = 34) and ?0.99 ± 1.05% (n = 24) over the respective 500‐6000 mL?min^?1 VO₂ and VCO₂ ranges. Validation results for the Oxycon Pro in breath‐by‐breath mode were ‐ 2.2 ± 1.6% (n = 12) for VO₂ and 5.7 ± 3.3% (n = 12) for VCO₂ over the 1000‐4000 mL?min^?1 range. On a Visual analog scale, participants reported improved breathing using the free‐flow indirect calorimetry (score 7.6 ± 1.2 vs 5.1 ± 2.7, P = 0.008). We conclude that total capturing free‐flow indirect calorimetry is suitable for measuring VO₂ even with the highest range. VO_2max was linear with the incline in P _max over the full range.     

A regression model applied to gender-specific ethanol elimination rates from blood and breath measurements in non-alcoholics

As elimination rates for alcohol are suggested to be gender specific, a novel regression model has been applied to estimate these rates for both men and women using experimentally measured data from 81 female and 96 male volunteers described in previous papers. Breath alcohol measurements were done with the Alcotest 7110 Evidential device and were coupled with concomitant sampling of venous blood. Statistical analyses involved use of a mixed linear model for blood alcohol concentration (BAC) and breath alcohol concentration (BrAC), respectively. The model takes regression lines for each test subject into account with an individual starting value (2 h after the end of drinking) and with an individual alcohol elimination rate per hour (coincidental effects). Further, the data was modeled so that an average alcohol elimination rate per hour could be estimated separately for both genders (constant effects). This enables us to methodically correctly estimate the back calculation. The elimination rates β ₆₀, which can be used for minimum and maximum back calculations for the BAC, were 0.115 g/kg/h and 0.260 g/kg/h, respectively, for women and 0.096 g/kg/h and 0.241 g/kg/h, respectively, for men. These figures widely deviate from gender-unspecific values commonly used in Germany (0.1 and 0.2 g/kg/h, respectively). The corresponding values for the BrAC were 0.061 mg/l/h and 0.124 mg/l/h for women and 0.049 mg/l/h and 0.112 mg/l/h for men. The probability of an over- or underestimation of the abovementioned extreme values is 0.3% in each case.     

Adaptations métaboliques à l'entraînement en début de saison de natation. Différences en fonction du sexe

Purpose – In this study, we compared the early metabolic adaptations to swim training between healthy men (n = 7) and women (n = 8).Methods – On the 1^st, 3^rd and 5^th testing sessions, plasma Fourier-transform infrared (FT-IR) spectra were obtained at the resting state and after each standardized testing session.Results – At the 1^st testing session, glycemia decreased more in females than in males (respectively, –1.101, –0.687 mmol.l^–1), triglycerides (TG) increased in females (0.184 mmol/l) and decreased in males (–0.094 mmol.l^–1) and males presented a higher plasma urea increase (p < 0.05). At the third testing session, glycemia increased in females (0.458 mmol.l^–1) whereas it decreased in males (–0.601 mmol.l^–1). Plasma urea increased more in males compared to females during exercise (p < 0.01). On the other hand, Apo B increased in females (0.063 g.l) and decreased in males (–0.073 g.l^–1) during exercise. At the 5^th testing session, males and females exhibited an equivalent metabolic response to exercise. However, IgA, IgG₁, IgG₃ and IgM were significantly different during exercise in males and females (p < 0.01) throughout the three sessions.Conclusions – Indeed, although metabolic adaptations to early phases of swim training were different, male and female subjects finally exhibited the same global metabolic response to endurance exercise. However immunity response to exercise in women and men was different throughout the three testing sessions.     

Reference values for and cross‐validation of time to exhaustion on a modified Balke protocol in Norwegian men and women

The aims of the present study were to provide reference values for time to exhaustion (TTE) on a modified Balke treadmill protocol, and to perform a cross‐validation of TTE as a measure of maximal oxygen consumption (VO_2max), in Norwegian men and women 20–85 years of age. Reference values for TTE were derived from a national sample of 765 subjects. An additional sample of 119 subjects was included in the cross‐validation (total n = 884), where prediction equations for VO_2max was established. A decline in TTE was seen with increased age. Prediction of VO_2max in an independent dataset (n = 319) resulted in a R² = 0.78 and standard error of the estimate = 4.55 mL/kg/min. The observed–predicted bias was small (mean difference <1.24 mL/kg/min), whereas random error was considerable (95% limits of agreement ± 7.11–9.70 mL/kg/min) across age in both men and women. Despite limitations concerning the prediction of VO_2max on an individual level, TTE from the Balke protocol is a good measure of aerobic fitness in adults across a range of settings, and could be evaluated according to the suggested reference values.     

A novel method to estimate adult age from the lumbar vertebral body using 3D PMCT images in Japanese

This study evaluated the age-related changes in the vertebral body using 3D Postmortem CT (PMCT) images and proposed an alternative age estimation formula. The PMCT images of 200 deceased individuals aged 25 to 99 years (126 males, 74 females) were retrospectively reviewed and included in the study. Using the open-source software ITK-SNAP and MeshLab, a 3D surface mesh of the fourth lumbar vertebral body (L4) and its convex hull models were created from the PMCT data. Using their inbuilt tools, volumes (in mm3) of the L4 surface mesh and convex hull models were subsequently computed. We derived VD, defined as the difference in volumes between the convex hull and L4 surface mesh normalized by L4 mesh volume, and VR, defined as the ratio of L4 mesh volume to convex hull volume based on individual L4. Correlation and regression analyses were performed between VD, VR, and chronological age. A statistically significant positive correlation (P < 0.001) between chronological age and VD, (r_s = 0.764, males; r_s = 0.725, females), and a significant negative correlation between chronological age and VR (r_s = -0.764, males; r_s = -0.725, females) was obtained in both sexes. The lowest standard error of the estimate was demonstrated by the VR at 11.9 years and 12.5 years for males and females, respectively. As such, their regression models to estimate adult age were Age = 248.9–2.5VR years, males; Age = 258.1–2.5VR years, females. These regression equations may be useful for estimating age in Japanese adults in forensic settings.     

Effects of hydration status during heat acclimation on plasma volume and performance

The impact of hydration status was investigated during a 5‐day heat acclimation (HA) training protocol vs mild/cool control conditions on plasma volume (PV) and performance (20 km time‐trial [TT]). Sub‐elite athletes were allocated to one of two heat training groups (90 min/day): (a) dehydrated to ~2% body weight (BW) loss in heat (35°C; DEH; n = 14); (b) euhydrated heat (35°C; EUH; n = 10), where training was isothermally clamped to 38.5°C core temperature (T_c). A euhydrated mild control group (22°C; CON; n = 9) was later added, with training clamped to the same relative heart rate (~75% HR_max) as elicited during DEH and EUH; thus all groups experienced the same internal training stress (%HR_max). Five‐day total thermal load was 30% greater (P < 0.001) in DEH and EUH vs CON. There were significant differences in the average percentage of maximal work rate (%W_max) across all groups (DEH: 24 ± 6%; EUH: 34 ± 9%; CON: 48 ± 8%W_max) during training required to elicit the same %HR_max (77 ± 4% HR_max). There were no significant differences pre‐to post‐HA between groups for PV (DEH: +1.7 ± 10.1%; EUH: +4.8 ± 10.2%; CON: +5.2 ± 4.0%), but there was a significant pooled group PV increase, as well as a 97% likely pooled improvement in TT performance (DEH: ?1.8 ± 2.8%; EUH: ?1.9 ± 2.1%, CON; ?1.8 ± 2.8%; P = 0.136). Due to a lack of between‐group differences for PV and TT, but pooled group increases in PV and 97% likely group increase in TT performance, over 5 days of intense training at the same average relative cardiac load suggests that overall training stress may also impact significant adaptations beyond heat and hydration stress.     

Multiparametric MRI Evaluation of Complex Ovarian Masses

ObjectiveTo assess the role of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in the categorization of complex ovarian masses into benign and malignant.Materials and MethodsThis prospective study was done on 33 complex ovarian masses. T1 and T2-weighted sequences, diffusion-weighted imaging, apparent diffusion coefficient, and dynamic contrast-enhanced magnetic resonance imaging were performed on 1.5 T MRI. Time-intensity curves, tissue signal intensity on unenhanced T1 images (SI₀), maximum absolute contrast enhancement (SI_max), time to reach SI_max (T_max), maximum relative SI (SI_rel = [SI_max ? SI₀]/SI₀ ×100), maximum Slope (Slope_max = SI_rel/T_max ×100), and wash in rate (WIR = [SI_max ? SI₀]/T_max) were calculated. Histopathological diagnosis was taken as gold standard.ResultsA total of 20/33 masses were benign, 2/33 were borderline tumors, and 11/33 were malignant. Diffusion restriction was seen in all malignant masses and 13/20 benign masses. The mean apparent diffusion coefficient values showed a significant difference between malignant and benign, with 81.8% sensitivity and 63.6% specificity. Type III curve showed 100% specificity for malignant lesions. T_max and Slope_max were useful in differentiating benign and malignant masses; with T_max cut-off at 73.5 seconds having a high specificity (81.8%) and Slope_max cut-off at 0.83%/s having high sensitivity (91%) and negative predictive value (94.4%).ConclusionMultiparametric MRI confers high diagnostic accuracy in stratifying complex ovarian masses.     

Match demands of professional Futsal: A case study

Despite its popularity and competitive status there have been only few scientific studies that have examined Futsal in professional players. Consequently the aim of this study was to examine the physiological responses and activity pattern to Futsal simulated game-play in professional players. Eight full-time professional outfield Futsal players volunteered for this study: age 22.4 (95% CI 18.8–25.3) years, body mass 75.4 (60–91) kg, height 1.77 (1.59–1.95) m and VO_2max 64.8 (53.8–75.8) ml kg^?1 min^?1. Physiological measurements were assessed during highly competitive training games (4 × 10-min quarters) and consisted of game VO₂, game blood-lactate concentration ([la]_b) and game heart rates (HRs). Game activities were assessed using a computerised video-analysis system. During simulated game-play players attained 75% (59–92) and 90% (84–96) of VO_2max and HR_max, respectively. Mean game VO₂ was 48.6 (40.1–57.1) ml kg^?1 min^?1. Peak game VO₂ and HRs were 99% (88–109) and 98% [90–106] of laboratory maximal values, respectively. Players spent 46 and 52% of the playing time at exercise intensities higher than 80 and 90% of VO_2max and HR_max, respectively. Mean [la]_b was 5.3 (1.1–10.4) mmol l^?1. Players covered 121 (105–137) m min^?1 and 5% (1–11) and 12% (3.8–19.5) of playing time spent performing sprinting and high-intensity running, respectively. On average players performed a sprint every ～79 s during play. These results show that Futsal played at professional level is a high-intensity exercise heavily taxing the aerobic and anaerobic pathways.     

Sex differences in cardiovascular demands of refereeing during international basketball competition

Objectives: The aim of this study was to investigate the impact of sex on cardiovascular responses of referees during elite international basketball competition.

Methods: Twenty-seven elite referees (9 female; 18 male) officiated a random sample of 18 matches during the final round of the 2013 Women’s Eurobasket Championship. Continuous recordings of referees’ heart rate (HR) during matches were obtained and analyzed for average HR, relative exercise intensity (% maximum HR, HR_max) and proportion of time spent within different exercise-intensity categories.

Results: During the championship, the average match HR was >150 bpm and approximated an exercise intensity of >85% HR_max for referees. Female referees exhibited lower average match HR (156.8 ± 10.2 vs. 163.6 ± 11.6 bpm, p<0.05) and exercise intensity (86.2 ± 5.5 vs. 89.5 ± 6.0% HR_max, p<0.05) compared to male referees. Referees spent most (>70%) of each match at a HR intensity of 70-89% HR_max with females experiencing more match time within the 55-69% HR_max category compared to males. Average HR and exercise intensity was greatest for all referees during the early part of the match (Quarter 1) that declined over the match.

Conclusion: This study has demonstrated that sex significantly influences cardiovascular responses for elite basketball referees with lower responses for females potentially reflective of different movement patterns. Reductions in cardiovascular response noted during matches for all referees may reflect alterations in metabolism, match activities or induction of fatigue that should be considered in the development and training of elite referees for optimal match performance.     

Adjuvant Thermal Accelerant Gel Use Increases Microwave Ablation Zone Temperature in Porcine Liver as Measured by MR Thermometry

PurposeTo determine the effects of a thermal accelerant gel on temperature parameters during microwave liver ablation.Materials and MethodsSixteen consecutive liver ablations were performed in 5 domestic swine under general anesthesia with (n = 8) and without (n = 8) administration of thermal accelerant gel. Ablation zone temperature was assessed by real-time MR thermometry, measured as maximum temperature (T_max) and the volume of tissue ≥ 60°C (V₆₀). Tissue heating rate, ablation zone shape, and thermal energy deposition using the temperature degree-minutes at 43°C (TDM43) index were also measured. Differences between groups were analyzed using generalized mixed modeling with significance set at P = .05.ResultsMean peak ablation zone temperature was significantly greater with thermal accelerant use (mean T_max, thermal accelerant: 120.0°C, 95% confidence interval [CI] 113.0°C–126.9°C; mean T_max, control: 80.3°C, 95% CI 72.7°C–88.0°C; P < .001), and a significantly larger volume of liver tissue achieved or exceeded 60°C when thermal accelerant was administered (mean V₆₀, thermal accelerant: 22.2 cm³; mean V₆₀, control: 15.9 cm³; P < .001). Significantly greater thermal energy deposition was observed during ablations performed with accelerant (mean TDM43, thermal accelerant: 198.4 min, 95% CI 170.7–230.6 min; mean TDM43, control: 82.8 min, 95% CI 80.5–85.1 min; P < .0001). The rate of tissue heating was significantly greater with thermal accelerant use (thermal accelerant: 5.8 min ± 0.4; control: 10.0 min; P < .001), and accelerant gel ablations demonstrated a more spherical temperature distribution (P = .002).ConclusionsThermal accelerant use is associated with higher microwave ablation zone temperatures, greater thermal energy deposition, and faster and more spherical tissue heating compared with control ablations.     

Hepatic steatosis is associated with increased hepatic FDG uptake

ObjectiveThe use of liver as a reference tissue for semi-quantification of tumour FDG uptake may not be valid in hepatic steatosis (HS). Previous studies on the relation between liver FDG uptake and HS have been contradictory probably because they ignored blood glucose (BG). Because hepatocyte and blood FDG concentrations equalize, liver FDG uptake parallels BG, which must therefore be considered when studying hepatic FDG uptake. We therefore re-examined the relation between HS and liver uptake taking BG into account.MethodsThis was a retrospective study of 304 patients undergoing routine PET/CT with imaging 60 min post-FDG. Average standard uptake value (SUV_ave), maximum SUV (SUV_max) and CT density (index of HS) were measured in a liver ROI. Blood pool SUV was based on the left ventricular cavity (SUV_LV). Correlations were assessed using least squares fitting of continuous data. Patients were also divided into BG subgroups (<4, 4–5, 5–6, 6–8, 8–10 and 10+ mmol/l).ResultsSUV_ave, SUV_max and SUV_LV displayed similar relations with BG. SUV_max/SUV_LV, but not SUV_ave/SUV_LV, correlated significantly with BG. SUV_max, but not SUV_ave, correlated inversely with CT density before and after adjusting for BG. SUV_max/SUV_ave correlated more strongly with CT density than SUV_max. CT density correlated inversely with SUV_max/SUV_LV but positively with SUV_ave/SUV_LV.ConclusionsHepatic SUV is more influenced by BG than by HS. Its relation with BG renders it unsuitable as a reference tissue. Nevertheless, hepatic fat does correlate positively with liver SUV, although this is seen only with SUV_max because SUV_ave is ‘diluted’ by hepatic fat.     

<Superscript>11</Superscript>C-methionine (MET) and <Superscript>18</Superscript>F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma

Purpose  The purpose of this prospective study was to clarify the individual and combined role of l-methyl-¹¹C-methionine-positron emission tomography (MET-PET) and 3′-deoxy-3′-[¹⁸F]fluorothymidine (FLT)-PET in tumor detection, noninvasive grading, and assessment of the cellular proliferation rate in newly diagnosed histologically verified gliomas of different grades. Materials and methods  Forty-one patients with newly diagnosed gliomas were investigated with MET-PET before surgery. Eighteen patients were also examined with FLT-PET. MET and FLT uptakes were assessed by standardized uptake value of the tumor showing the maximum uptake (SUV_max), and the ratio to uptake in the normal brain parenchyma (T/N ratio). All tumors were graded by the WHO grading system using surgical specimens, and the proliferation activity of the tumors were determined by measuring the Ki-67 index obtained by immunohistochemical staining. Results  On semiquantitative analysis, MET exhibited a slightly higher sensitivity (87.8%) in tumor detection than FLT (83.3%), and both tracers were 100% sensitive for malignant gliomas. Low-grade gliomas that were false negative on MET-PET also were false negative on FLT-PET. Although the difference of MET SUV_max and T/N ratio between grades II and IV gliomas was statistically significant (P < 0.001), there was a significant overlap of MET uptake in the tumors. The difference of MET SUV_max and T/N ratio between grades II and III gliomas was not statistically significant. Low-grade gliomas with oligodendroglial components had relatively high MET uptake. The difference of FLT SUV_max and T/N ratio between grades III and IV gliomas was statistically significant (P < 0.01). Again, the difference of FLT SUV_max and T/N ratio between grades II and III gliomas was not statistically significant. Grade III gliomas with non-contrast enhancement on MR images had very low FLT uptake. In 18 patients who underwent PET examination with both tracers, a significant but relatively weak correlation was observed between the individual SUV_max of MET and FLT (r = 0.54, P < 0.05) and T/N ratio of MET and FLT (r = 0.56, P < 0.05). Total FLT uptake in the tumor had a higher correlation (r = 0.89, P < 0.001) with Ki-67 proliferation index than MET uptake (r = 0.49, P < 0.01). Conclusions  PET studies using MET and FLT are useful for tumor detection in newly diagnosed gliomas. However, there is no complimentary information in tumor detection with simultaneous measurements of MET- and FLT-PET in low grade gliomas. FLT-PET seems to be superior than MET-PET in noninvasive tumor grading and assessment of proliferation activity in gliomas of different grades.     

Cardiorespiratory fitness in aging men and women: the DR's EXTRA study

The aim of the study was to describe the levels and to create reference values of cardiorespiratory fitness, expressed as maximal oxygen consumption (VO_2max), maximal metabolic equivalents (METs) and maximal workload in aging men and women. We measured VO_2max directly by a breath‐by‐breath method during a maximal exercise stress test on a bicycle ergometer with a linear workload increase of 20 W/min in a representative population sample of 672 men and 677 women aged 57–78 years. We presented the age and sex‐specific categories of cardiorespiratory fitness (very low, low, medium, high and very high) based on variable distribution and non‐linear regression models of VO_2max, maximal METs and maximal workload. The linear age‐related decrement of VO_2max was ?0.047 L/min/year (?2.3%) and ?0.404 mL/kg/min/year (?1.6%) in men and ?0.027 L/min/year (?1.9%) and ?0.328 mL/kg/min/year (?1.6%) in women. After exclusion of diseased individuals, the rate of VO_2max decrement remained similar. The number of chronic diseases (0, 1, 2 or ≥3) was inversely associated with VO_2max in men (P<0.001) and women (P<0.001). The present study provides clinically useful reference values of cardiorespiratory fitness for primary and secondary prevention purposes in aging people.     

Amide proton transfer-weighted MRI in the clinical setting – correlation with dynamic susceptibility contrast perfusion in the post-treatment imaging of adult glioma patients at 3T

IntroductionWe investigated the correlation between amide proton transfer-weighted magnetic resonance imaging (APTw MRI) and dynamic susceptibility contrast (DSC) perfusion in order to assess the potential of APTw MRI as an alternative to DSC in adult brain tumor (glioma) imaging.MethodsAfter Ethical Committee approval, forty adult patients, treated for histopathologically confirmed glioma (World Health Organization (WHO) grade II-IV), were prospectively imaged at 3 Tesla (3 T) with DSC perfusion and a commercially available three-dimensional (3D) APTw sequence. Two consultant neuroradiologists independently performed region of interest (ROI) measurements on relative cerebral blood volume (rCBV) and APTw maps, co-registered with anatomical images. The correlation APTw MRI-DSC perfusion was assessed using Spearman's rank-order test. Inter-observer agreement was evaluated by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) plots.ResultsA statistically significant moderately strong positive correlation was observed between maximum rCBV (rCBV_max) and maximum APTw (APTw_max) values (observer 1: r = 0.73; p < 0.01; observer 2: r = 0.62; p < 0.01). We found good inter-observer agreement for APTw_max (ICC = 0.82; 95% confidence interval (CI) 0.66–0.90), with somewhat broad outer 95% CI for the BA Limits of Agreement (LoA) (?1.6 to 1.9). ICC for APTw_max was higher than ICC for rCBV_max (ICC = 0.74; 95%; CI 0.50–0.86), but the difference was not statistically significant.ConclusionAPTw_max values correlate positively with rCBV_max in patients treated for brain glioma. APTw imaging is a reproducible technique, with some observer dependence. Results need to be confirmed by a larger population analysis.Implications for practiceAPTw MRI can be a useful addition to glioma follow-up imaging and a potential alternative to DSC perfusion, especially in patients where contrast agent is contraindicated.     

Adrenal masses: the value of additional fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in differentiating between benign and malignant lesions

Objective  To investigate whether integrated fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) can differentiate benign from adrenal malignant lesions on the basis of maximum standardized uptake value (SUV_max), tumor/liver (T/L) SUV_max ratio, and CT attenuation value (Hounsfield Units; HU) of unenhanced CT obtained from FDG-PET/CT data. Methods  We studied 30 patients with 35 adrenal lesions (16 adrenal benign lesions, size 16 ± 5 mm, in 15 patients; and 19 adrenal malignant lesions, 24 ± 12 mm, in 15 patients) who had confirmed primary malignancies (lung cancer in 23 patients, lymphoma in 2, esophageal cancer in 2, hypopharyngeal cancer in 1, prostate cancer in 1, and 1 patient in whom lesions were detected at cancer screening). All patients underwent PET/CT at 1 h post FDG injection. Diagnosis of adrenal malignant lesions was based on interval growth or reduction after chemotherapy. An adrenal mass that remained unchanged for over 1 year was the standard used to diagnose adrenal benign lesions. Values of FDG uptake and CT attenuation were measured by placing volumetric regions of interest over PET/CT images. Adrenal uptake of SUV_max ≥ 2.5 was considered to indicate a malignant lesion; SUV_max < 2.5 was considered to indicate a benign lesion. In further analysis, 1.8 was employed as the threshold for the T/L SUV_max ratio. Unenhanced CT obtained from PET/CT data was considered positive for adrenal malignant lesions based on a CT attenuation value ≥ 10 HU; lesions with a value < 10 HU were considered adrenal benign lesions. Mann–Whitney’s U test was used for statistical analyses. Results  SUV_max in adrenal malignant lesions (7.4 ± 3.5) was higher than that in adrenal benign lesions (2.1 ± 0.5, p < 0.05). The CT attenuation value of adrenal malignant lesions (27.6 ± 11.9 HU) was higher than that of adrenal benign lesions (10.1 ± 12.3 HU, p < 0.05). In differentiating between adrenal benign and malignant lesions, a CT threshold of 10 HU corresponded to a sensitivity of 57%, specificity of 94%, accuracy of 74%, positive predictive value of 92% and negative predictive value of 65%. An SUV_max cut-off value of 2.5 corresponded to a sensitivity of 89%, specificity of 94%, accuracy of 91%, positive predictive value of 94% and negative predictive value of 88%. The T/L SUV_max ratio was 1.0 ± 0.2 for adrenal benign lesions and 4.5 ± 3.0 for adrenal malignant lesions. And T/L SUV_max ratio cut-off value of 1.8 corresponded to a sensitivity of 85%, specificity of 100%, accuracy of 91%, positive predictive value of 100% and negative predictive value of 83%. Conclusions  FDG-PET/CT with additional SUV_max analysis improves the diagnostic accuracy of adrenal lesions in cancer patients.     

Effect of exercise on key pharmacokinetic parameters related to metformin absorption in healthy humans: A pilot study

Exercise is widely accepted as having therapeutic effects; thus, it is important to know whether it interacts with medications. The aim of the present pilot study was to examine the effect of high-intensity interval exercise (known to have antidiabetic action) on key pharmacokinetic parameters related to absorption of metformin (the first-line medication against type 2 diabetes). Ten healthy men participated in two sessions, spaced one to two weeks apart in random, counterbalanced order. In both sessions, participants received 1000 mg of metformin orally, 1-1.5 hours after breakfast. Then, they either ran for 60 minutes at alternating intensity, starting at 40 minutes after metformin administration, and rested without food consumption over the next 3 hours or they rested without food consumption during the entire testing period. Venous blood samples were collected before and at 0.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after metformin administration for metformin determination by liquid chromatography-mass spectrometry. Capillary blood samples were also collected for lactate and glucose measurements. Data from the two sessions were compared through Wilcoxon or Student's t test, as appropriate. Maximum plasma concentration of metformin (C_max) was higher at exercise compared to rest (P = .059). Time to reach C_max (T_max) decreased with exercise (P = .009), and the area under the metformin concentration vs time curve was higher at exercise (P = .047). The addition of exercise to metformin administration did not cause hypoglycemia or lactic acidosis. In conclusion, our results provide the first evidence that pharmacokinetic values related to metformin absorption are affected by exercise.