Individual differences in the kinetics of alcohol absorption and elimination

The individual differences in alcohol pharmacokinetics were studied using the one-compartment model with first-order absorption and zero-order elimination kinetics in humans. The blood alcohol concentrations (BACs) were simulated by obtained parameters, absorption rate constant (ka), and climination rate constant (β). The 81 healthy young Japanese volunteers, who had been divided into those without alcohol-induced facial flushing (nonflushers) and those with facial flushing (flushers) according to alcohol patch test results and a questionnaire beforehand, ingested 0.50 g/kg ethanol within 1 minute. Breath alcohol concentrations (BrACs) were measured during absorption and during the elimination period. BACs were obtained based on BrACs. Fifteen percent of subjects exhibited low BAC profile (below 0.4 mg/mL) (first-pass effect [FPE] group), although the majority showed normal BAC profile (normal group). The ka was approximately 5 to 8 (h⁻¹) in the normal group without significant difference between nonflushers and flushers, whereas that in the FPE group was significantly smaller than in the normal group. For the normal group, peak BACs were well simulated by the one-compartment model with first-order absorption and zero-order elimination kinetics. A considerable portion of subjects exhibited FPE. Absorption of alcohol from the intestine plays an important role in alcohol pharmacokinetics in humans.     

The elimination kinetics of methanol and the influence of ethanol

Summary Four male subjects aged between 20 and 29 years were given intravenous injections of methanol at a dosage of 10 mg per kg body weight, once without prior administration of ethanol, and once after oral ingestion of 0.3 g ethanol per kg body weight. The serum methanol concentration was monitored over the next 5 h (after methanol administration alone) and 6–7 h (after methanol administration following ethanol ingestion). The elimination of methanol administered alone was found to follow first-order kinetics with a rate constant for the elimination phase of 0.475-0.259 h⁻¹, corresponding to an elimination half-life of 1.8-3.0h. When ethanol was also administered methanol oxidation was found to be completely blocked until the blood ethanol concentration had fallen to 0.2 g/kg. When the ethanol concentration had dropped to zero, methanol elimination followed exactly the same course as that observed in the experiment without prior administration of ethanol (k: 0.378-0.231 h⁻¹;t _/12: 1.5–2.7 h).      

Top ten defence challenges among drinking drivers in Sweden.

This paper gives a review and opinion about defence challenges arising during the prosecution of drinking drivers in Sweden. The statutory limit of blood-alcohol concentration (BAC) is two-tiered; 0.2 mg/g (21 mg/100 ml) and 1.5 mg/g (159 mg/100 ml). In rank order of occurrence, the top ten defence challenges are shown in Table I. The hip-flask defence occurs in more than 90% of all challenges. Because the burden of proof in Swedish law rests on the prosecution, the charge of driving under the influence of alcohol is often dropped when alleged drinking after the offence is an issue.     

Driving under the influence of alcohol. A 5-year overview in Piedmont,Italy

Alcohol consumption represents a major health issue worldwide and a crucial factor in road accidences. This study provides information on the prevalence of alcohol in blood testing performed on 2752 subjects involved in vehicle accidents, which occurred in Piedmont (northern Italy) between 2008 and 2013. Blood alcohol concentration (BAC) was determined by an ISO 17025 accredited GC/MS procedure. Fifty-one % of positive samples showed BAC concentrations above 1.5 g/L, with a legal cut-off fixed at 0.5 g/L (and 0 g/L for specified categories such as novice and professional drivers). BAC values proved statistically different regarding the day of sampling (week or weekend days), age and gender, with a prevalence of positive results that reflects different drinking habits of a multifaceted population of alcohol consumers.     

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.     

Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

Purpose We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic β-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Methods Eight patients (aged 67 ± 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 ± 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [¹¹C]meta-hydroxy-ephedrine (HED) volume of distribution (V _d) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 ± 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 ± 6 years, p < 0.01 vs patients) data. Results MGU in patients was reduced in both normal remote (0.44 ± 0.14 μmol·min⁻¹·g⁻¹) and dysfunctional (0.49 ± 0.14 μmol·min⁻¹·g⁻¹) segments compared with controls (0.61 ± 0.7 μmol·min⁻¹·g⁻¹; p < 0.001 vs both). HED V _d was reduced in dysfunctional segments of patients (38.9 ± 21.2 ml·g⁻¹) compared with normal segments (52.2 ± 19.6 ml·g⁻¹) and compared with controls (62.7 ± 11.3 ml·g⁻¹). In patients, regional MGU was correlated with HED V _d. Conclusion The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts.     

Diagnostic ability of apparent diffusion coefficients for lymphomas and carcinomas in the pharynx

We evaluated the diagnostic ability of diffusion-weighted imaging for the differentiation between lymphomas and carcinomas in the pharynx and between carcinomas with different histological types in the pharynx. T1-weighted, fat-suppressed T2-weighted, and diffusion-weighted MR imaging was performed on 14 patients with pharyngeal lymphomas, 26 patients with carcinomas of the pharynx, 5 patients with adenoidal hypertrophy, and 22 patients with normal tonsils. Apparent diffusion coefficients (ADCs) were determined by using two b factors (500 and 1,000 s/mm²). The ADCs of lymphomas were significantly smaller (0.454 ± 0.075 × 10⁻³ mm²/s) than those of carcinomas (0.863 ± 0.238 × 10⁻³ mm²/s). The ADCs of poorly differentiated and undifferentiated carcinomas (0.691 ± 0.149 × 10⁻³ mm²/s) were significantly smaller than those of moderately differentiated and well-differentiated carcinomas (0.971 ± 0.221 × 10⁻³ mm²/s), but were significantly larger than those of lymphomas. When an ADC smaller than 0.560 × 10⁻³ mm²/s was used for predicting lymphomas, we obtained the highest accuracy of 96%, with 100% sensitivity and 94% specificity, 86% positive predictive value, and 100% negative predictive value. Therefore, ADC measurements effectively differentiate lymphomas from carcinomas in the pharynx and could be a useful adjunct to biopsy-based development of treatment planning.     

Simultaneous evaluation of myocardial blood flow,cardiac function and lung water content using [<Superscript>15</Superscript>O]H<Subscript>2</Subscript>O and positron emission tomography

Purpose This study sought to evaluate an imaging approach using [¹⁵O]H₂O and positron emission tomography (PET) for simultaneous assessment of myocardial perfusion, cardiac function and lung water content as a potential indicator of pulmonary oedema. Methods Twenty-six subjects divided into two groups (group I, 13 patients with idiopathic dilated cardiomyopathy; group II, 13 healthy volunteers) underwent dynamic PET scanning after intravenous infusion of ≈995 MBq [¹⁵O]H₂O. In both groups, echocardiograms were performed after the PET studies. From the dynamic [¹⁵O]H₂O data, lung water content (LWC) at equilibrium, myocardial blood flow (MBF), cardiac output (CO), stroke volume (SV) and stroke volume indexes (SVI) using the indicator dilution principle were determined. Results LWC was 18% (p = 0.038) higher in patients than in controls. Global MBF did not differ significantly between the groups, but regional MBF values were significantly lower (p < 0.05) in the anterior and septal walls in the patient group. The results of the Passing-Bablok regression indicated the absence of a systematic difference between the two techniques. Bland-Altman analysis performed for each group (patients vs healthy controls) showed a non-significant bias (p > 0.1) of −0.02 ± 0.82 vs −0.05 ± 0.54 l/min (CO), −1.44 ± 14.31 vs 1.70 ± 10.56 ml/beat (SV) and 0.47 ± 6.21 vs 0.30 ± 5.02 ml/beat/m² (SVI). The 95% limits of agreement were −1.62 to 1.59 vs −1.11 to 1.01 l/min (CO), −26.61 to 29.49 vs −22.39 to 18.99 ml/beat (SV) and −11.69 to 12.88 vs −9.53 to 10.14 ml/beat/m² (SVI). Right ventricular CO was increased by 33% (p = 0.014) in the patient group as compared with normal controls. Conclusion Our results demonstrate that additional analysis of cardiac function and lung water content are feasible from the dynamic cardiac [¹⁵O]H₂O PET studies acquired for myocardial perfusion. The parameters appear to work as expected. Further studies are warranted to elucidate the clinical value of these new parameters. This study was financially supported by grants from Turku University Hospital (EVO) and Finnish Foundation for Cardiovascular Research.     

Kinetics in serum and urinary excretion of ethyl sulfate and ethyl glucuronide after medium dose ethanol intake

The direct ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are of increasing importance for clinical and forensic applications, but there are only few studies on the kinetics of EtG in serum and none on EtS. In this study, 13 volunteers (social drinkers) drank ethanol in the form of white wine to reach a blood alcohol concentration of 0.51 ± 0.17 g/kg, and blood and urine samples were analyzed for EtG and EtS simultaneously by chromatography-tandem mass spectrometry (LC-MS/MS). Mean peak serum EtG and EtS concentrations were 2.9 ± 1.3 and 2.8 ± 1.6 μmol/l, respectively, and were reached between 4.0 ± 0.9 h after the start of drinking (3.0 ± 0.5 h for EtS). The mean time differences between reaching maximum blood ethanol levels and serum metabolite levels were 2.3 ± 0.9 h for EtG and 1.2 ± 0.5 h for EtS. In the last blood samples collected (10–11 h after the start of drinking), 11 (of 13) volunteers were still positive for EtG in serum, whereas only 2 were positive for EtS. In the serum of one female person, no EtS was detectable at any time; however, it was excreted in the urine in (low) concentrations. Ethanol was detectable in the serum for up to 8.6 h after the start of drinking, whereas EtG and EtS were detectable up to more than 5.8 h (EtG) and 4.0 h (EtS), respectively. Mean peak urinary concentrations were 401 ± 232 μmol/l for EtG and 266 ± 153 μmol/l for EtS, and mean peak levels were reached 6.2 ± 0.9 h (EtG) and 5.3 ± 1.2 h (EtS) after the start of drinking. Maximum concentrations of EtG and EtS in serum showed a wide interindividual variation and could not be correlated to the maximum blood ethanol concentrations. Correlations (p < 0.001, Kendall’s Tau b) were found when comparing pairs of parameters, but mostly involved areas under the curve (AUC) of metabolites or of ethanol; one correlation linked the peak concentrations of EtG and EtS in urine. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Diffusion-weighted MR imaging of abdominopelvic abscesses

This study was conducted to determine the incremental value of diffusion-weighted MR imaging (DW-MRI) over T2-weighted imaging diagnosing abdominopelvic abscesses and compare apparent diffusion coefficient (ADC) values of abscesses and non-infected ascites. In this IRB-approved, HIPAA-compliant study, two radiologists retrospectively compared T2-weighted, T2-weighted + DW-MRI and T2-weighted + contrast enhanced MR images of 58 patients (29 with abscess, 29 with ascites) who underwent abdominal MRI for abscess detection. Confidence and sensitivity was compared using McNemar’s test. ADC of abscesses and ascites was compared by t test, and a receiver operating characteristic (ROC) curve was constructed. Detection of abscesses and confidence improved significantly when T2-weighted images were combined with DW-MRI (sensitivity: observer 1—100%, observer 2—96.6%) or contrast enhanced images (sensitivity: both observers—100%) compared to T2-weighted images alone (sensitivity: observer 1—65.5%, observer 2—72.4%). All abscesses showed restricted diffusion. Mean ADC of abscesses (observer 1—1.17 ± 0.42 × 10⁻3 mm2/s, observer 2—1.43 ± 0.48 × 10⁻³ mm2/s) was lower than ascites (observer 1—3.57 ± 0.68 × 10⁻³ mm2/s, observer 2—3.42 ± 0.67 × 10⁻³ mm2/s) (p < 0.01). ROC analysis showed perfect discrimination of abscess from ascites with threshold ADC of 2.0 × 10⁻³ mm2/s (Az value 1.0). DW-MRI is a valuable adjunct to T2-weighted images diagnosing abdominopelvic abscesses. ADC measurements may have the potential to differentiate abdominal abscesses from ascites.     

Characterization of pediatric head and neck masses with diffusion-weighted MR imaging

We aimed to assess the clinical usefulness of the ADCs calculated from diffusion-weighted echo-planar MR images in the characterization of pediatric head and neck masses. This study included 78 pediatric patients (46 boys and 32 girls aged 3 months–15 years, mean 6 years) with head and neck mass. Routine MR imaging and diffusion-weighted MR imaging were done on a 1.5-T MR unit using a single-shot echo-planar imaging (EPI) with a b factor of 0.500 and 1,000 s mm⁻². The ADC value was calculated. The mean ADC values of the malignant tumours, benign solid masses and cystic lesions were (0.93 ± 0.18) × 10⁻³, (1.57 ± 0.26) × 10^–3 and (2.01 ± 0.21 )× 10^–3 mm² s⁻¹, respectively. The difference in ADC value between the malignant tumours and benign lesions was statistically significant (p < 0.001). When an apparent diffusion coefficient value of 1.25 × 10^–3 mm² s⁻¹ was used as a threshold value for differentiating malignant from benign head and neck mass, the best results were obtained with an accuracy of 92.8%, sensitivity of 94.4%, specificity of 91.2%, positive predictive value of 91% and negative predictive value of 94.2%. Diffusion-weighted MR imaging is a new promising imaging approach that can be used for characterization of pediatric head and neck mass.     

Diffusion-weighted MR imaging (DWI) in the evaluation of epidural spinal lesions

Introduction Epidural spinal cord compression is one of the most critical emergency conditions requiring medical attention and requires prompt and adequate treatment. The aim of our study was to assess the role of diffusion-weighted magnetic resonance (MR) imaging (DWI) in the diagnosis and differentiation of epidural spinal lesions. Methods Three patients with epidural lymphoma, two with sarcoma and three with epidural metastatic disease were imaged on a 1.5T MRI unit. DWI was performed using navigated, interleaved, multi-shot echo planar imaging (IEPI). Three region of interest (ROI)-measurements were obtained on corresponding apparent diffusion coefficient (ADC) maps, and the mean ADC value was used for further analysis. The cellularity of tumors was determined as the N/C ratio (nucleus/cytoplasma ratio) from histological samples. The ADC values and N/C ratios of lesions were compared using a Kruskal-Wallis test. Results The mean ADC of the lymphomas was 0.66 × 10⁻³ mm²/s, that of the sarcomas was 0.85 × 10⁻³ mm²/s and the ADC of the metastatic lesions was 1.05 × 10⁻³ mm²/s; however, the differences were not statistically significant. Mean N/C ratios in the lymphoma, sarcomas and metastases were 4:1, 2:1, and 2.6:1, respectively, with a statistically significant difference between the groups (p < 0.025). Conclusion Although not statistically significant due to the small patient sample, our results clearly show a tendency toward decreased diffusivity in neoplastic lesions with higher cellularity. The data from our study suggest that DWI is a feasible and potentially useful technique for the evaluation of epidural lesions that cause spinal cord compression on a per-patient basis.     

Population and segregation data on 17 Y-STRs: results of a GEP-ISFG collaborative study

A collaborative work was carried out by the Spanish and Portuguese International Society for Forensic Genetics Working Group in order to extend the existing data on Y-short tandem repeat (STR) mutations at the 17 Y chromosome STR loci included in the AmpFlSTR YFiler kit (Applied Biosystems): DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, and GATA H4.1. In a sample of 701 father/son pairs, 26 mutations were observed among 11,917 allele transfers across the 17 loci. After summing previously reported mutation data with our sample, mutation rates varied between 4.25 × 10⁻⁴ (95% CI 0.05 × 10⁻³–1.53 × 10⁻³) at DYS438 and 6.36 × 10⁻³ (95% CI 2.75 × 10⁻³–12.49 × 10⁻³) at DYS458. All mutations were single step, and mutations in the same father/son pair were found twice. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Comparison of MRI (including SS SE-EPI and SPIO-enhanced MRI) and FDG-PET/CT for the detection of colorectal liver metastases

Fluoro-18-deoxyglucose positron emission tomography computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI), including unenhanced single-shot spin-echo echo planar imaging (SS SE-EPI) and small paramagnetic iron oxide (SPIO) enhancement, were compared prospectively for detecting colorectal liver metastases. Twenty-four consecutive patients suspected for metastases underwent MRI and FDG-PET/CT. Fourteen patients (58%) had previously received chemotherapy, including seven patients whose chemotherapy was still continuing to within 1 month of the PET/CT study. The mean interval between PET/CT and MRI was 10.2 ± 5.2 days. Histopathology (n = 18) or follow-up imaging (n = 6) were used as reference. Seventy-seven metastases were detected. In nine patients, MRI and PET/CT gave concordant results. Sensitivities for unenhanced SS SE-EPI, MRI without SS SE-EPI and FDG-PET/CT were, respectively, 100% (p = 9 × 10⁻¹⁰ vs PET, p = 8 × 10⁻³ vs MRI without SS SE-EPI), 90% (p = 2 × 10⁻⁷ vs PET) and 60%. PET/CT sensitivity dropped significantly with decreasing size, from 100% in lesions larger than 20 mm (identical to MRI), over 54% in lesions between 10 and 20 mm (p = 3 × 10⁵ versus unenhanced SS SE-EPI), to 32% in lesions under 10 mm (p = 6 × 10⁻⁵ versus unenhanced SS SE-EPI). Positive predictive value of PET was 100% (identical to MRI). MRI, particularly unenhanced SS SE-EPI, has good sensitivity and positive predictive value for detecting liver metastases from colorectal carcinoma. Its sensitivity is better than that of FDG-PET/CT, especially for small lesions.     

Structural alterations of the coronary arterial wall are associated with myocardial flow heterogeneity in type 2 diabetes mellitus

Purpose  To determine the relationship between carotid intima–media thickness (IMT), coronary artery calcification (CAC), and myocardial blood flow (MBF) at rest and during vasomotor stress in type 2 diabetes mellitus (DM). Methods  In 68 individuals, carotid IMT was measured using high-resolution vascular ultrasound, while the presence of CAC was determined with electron beam tomography (EBT). Global and regional MBF was determined in milliliters per gram per minute with ¹³N-ammonia and positron emission tomography (PET) at rest, during cold pressor testing (CPT), and during adenosine (ADO) stimulation. Results  There was neither a relationship between carotid IMT and CAC (r = 0.10, p = 0.32) nor between carotid IMT and coronary circulatory function in response to CPT and during ADO (r = −0.18, p = 0.25 and r = 0.10, p = 0.54, respectively). In 33 individuals, EBT detected CAC with a mean Agatston-derived calcium score of 44 ± 18. There was a significant difference in regional MBFs between territories with and without CAC at rest and during ADO-stimulated hyperemia (0.69 ± 0.24 vs. 0.74 ± 0.23 and 1.82 ± 0.50 vs. 1.95 ± 0.51 ml/g/min; p ≤ 0.05, respectively) and also during CPT in DM but less pronounced (0.81 ± 0.24 vs. 0.83 ± 0.23 ml/g/min; p = ns). The increase in CAC was paralleled with a progressive regional decrease in resting as well as in CPT- and ADO-related MBFs (r = −0.36, p ≤ 0.014; r = −0.46, p ≤ 0.007; and r = −0.33, p ≤ 0.041, respectively). Conclusions  The absence of any correlation between carotid IMT and coronary circulatory function in type 2 DM suggests different features and stages of early atherosclerosis in the peripheral and coronary circulation. PET-measured MBF heterogeneity at rest and during vasomotor stress may reflect downstream fluid dynamic effects of coronary artery disease (CAD)-related early structural alterations of the arterial wall.     

Detection and quantification of the age-related sjTREC decline in human peripheral blood

The decline of signal joint T-cell receptor rearrangement excision circles (sjTRECs) in human peripheral blood has been demonstrated to be age-related, which can be a potential marker for individual age determination. However, little is known about the quantitative relationship between the levels of sjTREC and age. The aim of the present study was to investigate the levels of sjTREC in peripheral blood leukocytes (PBLs) among different age groups in Chinese population, so as to clarify whether it could serve as a suitable marker for biological age estimation in forensic practice. sjTREC levels were measured by real-time quantitative PCR analysis in peripheral blood samples from individuals of known age (n = 248). The quantification results showed that sjTREC declined in human PBLs in an age-dependent manner (r = −0.8177, P < 0.01). The formula for age estimation based on peripheral sjTREC decline was Y = −24.921x − 39.932 ± 10.47 (Y age, year; X log sjTREC/TBP; 10.47: standard error). Furthermore, there was no difference between males and females with regard to sjTREC levels. These results suggest that assessment of sjTREC in PBLs might be a valuable additional tool in age determination, especially in cases where traditional morphologic information is absent or inefficient in forensic practice.     

Noninvasive functional imaging of P-glycoprotein-mediated doxorubicin resistance in a mouse model of hereditary breast cancer to predict response,and assign P-gp inhibitor sensitivity

Purpose  Using a “spontaneous” mammary mouse tumor model we set out to develop diagnostic approaches for non-invasive P-glycoprotein (P-gp) staging and response prediction. Methods   ^99mTc-MIBI efflux rates were measured using a gamma camera in three Brca1 ^−/−; p53 ^−/− mouse mammary tumors that have different Mdr1a/b expression levels. The efflux rates were quantified in the 10–30-min period after injection. In addition to the P-gp-mediated efflux measurements in untreated tumors, efflux measurements were performed in the presence of the P-gp inhibitor tariquidar. Volumetric doxorubicin response patterns for the different tumors were determined and correlated with the efflux rates. Results  Combined pre- and post-inhibitor treatment imaging of P-gp-mediated efflux correlated with Mdr1a/b expression: basal (0.0026, p = 0.16), 3-fold Mdr1a/b (0.0074, p = 0.02), and 17-fold Mdr1a and 46-fold Mdr1b (0.012, p = 0.002). Based on the doxorubicin response of these tumors, we generated a computer-aided diagnosis model that predicts the likelihood of drug resistance. Conclusions  Quantified ^99mTc-MIBI efflux has potential to: (1) noninvasively assign Mdr1 expression levels, (2) predict the therapeutic impact of a P-gp inhibitor, and (3) noninvasively assess the probability of drug resistance.     

Determinants of the response of left ventricular ejection fraction to vasodilator stress in electrocardiographically gated 82rubidium myocardial perfusion PET

Purpose Myocardial perfusion imaging with ⁸²Rb PET allows for ECG-gated studies to be obtained early after radiotracer injection, capturing ventricular function close to peak pharmacologic action of dipyridamole. This is different from gated SPECT and may potentially provide additional diagnostic information. We sought to identify potential correlates of the PET-derived ejection fraction response to vasodilator stress. Methods One hundred ten consecutive patients undergoing ⁸²Rb PET myocardial perfusion imaging during evaluation for coronary artery disease were included. Using a GE Discovery STRx PET-CT scanner, ECG-gated images (eight bins) were obtained at rest and 4 min after dipyridamole infusion, 90 s after infusion of 1,480–2,220 MBq of ⁸²Rb. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were determined using a five-point scoring system and 20-segment model. Ejection fraction was calculated using automated QGS software. Results Significant reversibility (SDS ≥ 4) was found in 23 patients (21%). Mean LVEF in all patients was 47 ± 13% at rest and 53 ± 13% during dipyridamole. LVEF increased in 89 patients, and decreased in 17 patients during vasodilation. The change in LVEF was inversely correlated with SDS (r = −0.26; p = 0.007). Additionally, it was inversely correlated with resting LVEF (r = −0.20; p = 0.03) and SSS (r = −0.25; p = 0.009). No significant correlations were observed with SRS, heart rate, blood pressure, age, hypertension, hypercholesterolemia, or pretest likelihood of disease. At multivariate regression analysis, SDS was an independent predictor of the change in LVEF. Conclusions Gated ⁸²Rb PET during pharmacologic stress allows for assessment of the functional response to vasodilation. The magnitude of LVEF increase is determined by stress perfusion/reversible perfusion defects. Functional response to hyperemia may thus be incorporated in future evaluations of diagnostic and prognostic algorithms based on ⁸²Rb PET.     

Determination of phosphatidyl ethanol (PEth) 16:0/18:1 in dried blood samples of drivers involved in traffic accidents: A pilot study

In routine forensic toxicology practices, blood alcohol concentration (BAC) levels are measured in traffic accidents that ended up in emergency departments. Nevertheless, since the elimination of ethanol from the blood is fast and the detection time is short, BAC cannot indicate the occurrence of chronic excessive alcohol consumption. Phosphatidylethanol (PEth) is a unique ethanol direct biomarker that occurs only in the presence of phospholipase D enzyme in erythrocyte membranes during alcohol intake, and it indicates alcohol intake.In this study, both whole blood and dried blood samples were collected from 50 patients who were admitted to Cukurova University Hospital Emergency Department due to a traffic accident. While studying BAC in whole blood samples, PEth 16:0/18:1 analysis was performed on dried blood samples by LC-MS/MS.According to the BAC (50 mg/dL) value, the legal limit in Turkey, the optimal threshold PEth 16:0/18:1 value was set as 160 ng/mL and over. This study determined that 15 people with above PEth 16:0/18:1 concentrations above 160 ng/mL were classified as excessive alcohol consumption.The data obtained in this study showed a positive correlation between BAC and PEth concentration when driving under the influence of ethanol.     

Combined use of T2-weighted and diffusion-weighted 3-T MR imaging for differentiating uterine sarcomas from benign leiomyomas

The objective of our study was to compare diffusion-weighted imaging (DWI) alone and DWI combined with T2-weighted MRI for the differentiation of uterine sarcomas from benign leiomyomas. T2-weighted imaging and DWI were performed in 103 patients with 103 myometrial tumours, including 8 uterine sarcomas and 95 benign leiomyomas on 3-T MR imaging. The signal intensity (SI) of the tumour on T2-weighted images was quantified as the tumour–myometrium contrast ratio (TCR) by using the following formula: (SI_tumour − SI_myometrium)/SI_myometrium. The TCR or apparent diffusion coefficient (ADC) value alone and then the ADC value combined with T2-weighted imaging were evaluated for differentiation between sarcomas and leiomyomas. The mean ADC value of sarcomas was 0.86 ± 0.11 × 10⁻³ m²/s, which was significantly lower than that of leiomyomas 1.18 ± 0.24 × 10⁻³ m²/s; however, there was a substantial overlap. The mean TCR of sarcomas was 0.66 ± 0.71, which was significantly higher than that of the leiomyomas, –0.37 ± 0.34; however, again, there was a considerable overlap. When ADC was less than 1.05 × 10⁻³ mm²/s and TCR was greater than 0 this condition was considered to confirm a sarcoma; a combination of ADC and TCR achieved a significant improvement without any overlap between sarcomas and leiomyomas (sensitivity 100%, specificity 100%). Our preliminary results indicate that combined DWI and T2-weighted MR imaging is better than DWI alone in the differentiation of uterine sarcomas from benign leiomyomas.