Late Blood Samples Research Articles

Robust Porcine GFR Measurement with Radiotracers and Only Late Blood Samples

(1) Pigs are physiologically very relevant as animal models of human physiology. Radiotracer methods for porcine GFR (glomerular filtration rate) determination exist but require full-curve blood sampling or the application of correction formulas, which vary among studies. (2) We used porcine GFR data (40 datapoints from 20 juvenile pigs) for which the GFR was measured as the plasma clearance of [99mTc]Tc-DTPA. The reference clearance (Cl, GFR; range 41–85 mL/min) was measured from the full curve under the data. For simpler determination, an approximate clearance, Cl1, was based on the last five blood samples (acquired 120–240 min post injection). (3) The following formula for the GFR was developed: Cl = 1.27 · (Cl1)0.92. The spread (SD) was within 4% of the reference GFR. A comparison with the literature data showed that our correction formula was robust in pigs of various breeds, sizes up to approximately 200 kg, and GFRs up to approximately 400 mL/min, with a spread of up to 8%. The formula was also applicable for iohexol as the tracer. (4) A formula was developed that allows porcine GFR to be measured using only 4–5 late blood samples. This new formula can be applied across a wide range of swine breeds, animal sizes, and GFR ranges, allowing for robust determination of the GFR in pigs without full-curve blood sampling and without urine collection.

Metabolomic Profiles of Nonobese and Obese Women With Gestational Diabetes.

To examine whether nonobese (BMI<30 kg/m2) and obese (BMI≥30 kg/m2) women with gestational diabetes mellitus (GDM) and obese non-GDM women differ in metabolomic profiles from nonobese non-GDM controls. Levels of 66 metabolic measures were assessed in early (median 13, IQR 12.4-13.7 gestation weeks), and across early, mid (20, 19.3-23.0) and late (28, 27.0-35.0) -pregnancy blood samples in 755 pregnant women of the PREDO and RADIEL studies. The independent replication cohort comprised 490 pregnant women. Nonobese and obese GDM, and obese non-GDM women differed similarly from the controls across early, mid, and late pregnancy in 13 measures, including VLDL-related measures, and fatty acids. In 6 measures, including fatty acid ratios, glycolysis-related measures, valine and 3-hydroxybutyrate, the differences between obese GDM women and controls were more pronounced than the differences between nonobese GDM or obese non-GDM women and controls. In 16 measures, including HDL-related measures, fatty acid ratios, amino acids and inflammation, differences between obese GDM or obese non-GDM women and controls were more pronounced than the differences between nonobese GDM women and controls. Most differences were evident in early pregnancy, and in the replication cohort were more often in the same direction than would be expected by chance alone. Differences between nonobese and obese GDM, or obese non-GDM women and controls in metabolomic profiles may allow detection of high-risk women for timely targeted preventive interventions.

Machine learning-based approach reveals essential features for simplified TSPO PET quantification in ischemic stroke patients

IntroductionNeuroinflammation evaluation after acute ischemic stroke is a promising option for selecting an appropriate post-stroke treatment strategy. To assess neuroinflammation in vivo, translocator protein PET (TSPO PET) can be used. However, the gold standard TSPO PET quantification method includes a 90 min scan and continuous arterial blood sampling, which is challenging to perform on a routine basis. In this work, we determine what information is required for a simplified quantification approach using a machine learning algorithm. Materials and MethodsWe analyzed data from 18 patients with ischemic stroke who received 0–90 min [18F]GE-180 PET as well as T1-weigted (T1w), FLAIR, and arterial spin labeling (ASL) MRI scans. During PET scans, five manual venous blood samples at 5, 15, 30, 60, and 85 min post injection (p.i.) were drawn, and plasma activity concentration was measured. Total distribution volume (VT) was calculated using Logan plot with the full dynamic PET and an image-derived input function (IDIF) from the carotid arteries. IDIF was scaled by a calibration factor derived from all the measured plasma activity concentrations. The calculated VT values were used for training a random forest regressor. As input features for the model, we used three late PET frames (60–70, 70–80, and 80–90 min p.i.), the ASL image reflecting perfusion, the voxel coordinates, the lesion mask, and the five plasma activity concentrations. The algorithm was validated with the leave-one-out approach. To estimate the impact of the individual features on the algorithm’s performance, we used Shapley Additive Explanations (SHAP). Having determined that the three late PET frames and the plasma activity concentrations were the most important features, we tested a simplified quantification approach consisting of dividing a late PET frame by a plasma activity concentration. All the combinations of frames/samples were compared by means of concordance correlation coefficient and Bland-Altman plots. ResultsWhen using all the input features, the algorithm predicted VT values with high accuracy (87.8 ± 8.3%) for both lesion and non-lesion voxels. The SHAP values demonstrated high impact of the late PET frames (60–70, 70–80, and 80–90 min p.i.) and plasma activity concentrations on the VT prediction, while the influence of the ASL-derived perfusion, voxel coordinates, and the lesion mask was low. Among all the combinations of the late PET frames and plasma activity concentrations, the 70–80 min p.i. frame divided by the 30 min p.i. plasma sample produced the closest VT estimate in the ischemic lesion. ConclusionReliable TSPO PET quantification is achievable by using a single late PET frame divided by a late blood sample activity concentration.

Short 2-[18F]Fluoro-2-Deoxy-D-Glucose PET Dynamic Acquisition Protocol to Evaluate the Influx Rate Constant by Regional Patlak Graphical Analysis in Patients With Non-Small-Cell Lung Cancer.

Purpose: To test a short 2-[18F]Fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET dynamic acquisition protocol to calculate Ki using regional Patlak graphical analysis in patients with non-small-cell lung cancer (NSCLC).Methods: 24 patients with NSCLC who underwent standard dynamic 2-[18F]FDG acquisitions (60 min) were randomly divided into two groups. In group 1 (n = 10), a population-based image-derived input function (pIDIF) was built using a monoexponential trend (10–60 min), and a leave-one-out cross-validation (LOOCV) method was performed to validate the pIDIF model. In group 2 (n = 14), Ki was obtained by standard regional Patlak plot analysis using IDIF (0–60 min) and tissue response (10–60 min) curves from the volume of interests (VOIs) placed on descending thoracic aorta and tumor tissue, respectively. Moreover, with our method, the Patlak analysis was performed to obtain Ki,s using IDIFFitted curve obtained from PET counts (0–10 min) followed by monoexponential coefficients of pIDIF (10–60 min) and tissue response curve obtained from PET counts at 10 min and between 40 and 60 min, simulating two short dynamic acquisitions. Both IDIF and IDIFFitted curves were modeled to assume the value of 2-[18F]FDG plasma activity measured in the venous blood sampling performed at 45 min in each patient. Spearman's rank correlation, coefficient of determination, and Passing–Bablok regression were used for the comparison between Ki and Ki,s. Finally, Ki,s was obtained with our method in a separate group of patients (group 3, n = 8) that perform two short dynamic acquisitions.Results: Population-based image-derived input function (10–60 min) was modeled with a monoexponential curve with the following fitted parameters obtained in group 1: a = 9.684, b = 16.410, and c = 0.068 min−1. The LOOCV error was 0.4%. In patients of group 2, the mean values of Ki and Ki,s were 0.0442 ± 0.0302 and 0.33 ± 0.0298, respectively (R2 = 0.9970). The Passing–Bablok regression for comparison between Ki and Ki,s showed a slope of 0.992 (95% CI: 0.94–1.06) and intercept value of −0.0003 (95% CI: −0.0033–0.0011).Conclusions: Despite several practical limitations, like the need to position the patient twice and to perform two CT scans, our method contemplates two short 2-[18F]FDG dynamic acquisitions, a population-based input function model, and a late venous blood sample to obtain robust and personalized input function and tissue response curves and to provide reliable regional Ki estimation.

Biomarkers of Inflammation and Fibrosis in Kawasaki Disease Patients Years After Initial Presentation With Low Ejection Fraction.

BackgroundCoronary artery aneurysms and myocarditis are well‐recognized complications of Kawasaki disease (KD) but no systematic evaluation of the consequences of myocarditis has been performed in the subset presenting with low ejection fraction (EF). We postulated that more severe myocardial inflammation as evidenced by low EF during the acute phase could lead to late myocardial fibrosis.Methods and ResultsWe measured the carboxyterminal propeptide of procollagen type I (PIPC), soluble suppressor of tumorigenicity 2, galectin‐3 (Gal‐3), growth‐differentiation factor‐15, and calprotectin by ELISA in late convalescent blood samples from 16 KD patients who had an EF ≤55% on their initial echocardiogram. Results were compared with samples from sex‐ and age‐matched KD patients with initial EF >60%. In the univariate analysis, the median Gal‐3 and PIPC levels in the low EF group were significantly higher than those in the normal EF group (Gal‐3: low EF 6.216 versus normal EF 4.976 mg/dL P=0.038, PIPC: low EF 427.4 versus normal EF 265.2 mg/dL, P=0.01). In a multivariable analysis, there were significant differences for Gal‐3 and PIPC levels between the low and normal EF groups, adjusting for age, sex, and worst z score.ConclusionsConvalescent KD patients with a history of low EF during the acute illness had significantly elevated levels of Gal‐3 and PIPC when compared with matched‐control KD patients with normal EF. These findings raise concern for myocardial fibrosis as a potential late sequela of the more severe myocarditis experienced by a subset of KD patients during the acute phase.

Prediction of birth weight small for gestational age with and without preeclampsia by angiogenic markers: an Odense Child Cohort study

Purpose: To investigate the predictive performance of placental growth factor (PlGF) and soluble FMS-like kinase 1 (sFlt-1) on birth weight and small for gestational age (SGA), in a large, population-based cohort.Methods: Women enrolled in the population-based, prospective Odense Child Cohort Study with early (GA < 20 weeks) and/or late (≥20 weeks) pregnancy blood samples (n = 1937) were included. The association between log-transformed values of the biomarkers and birth weight Z-score was studied using multivariate regression models. The prediction of SGA overall, and in women developing preeclampsia, by biomarkers was evaluated using receiver operating characteristic analyses.Results: No substantial associations between early pregnancy biomarkers and SGA were seen. PlGF measured in late pregnancy demonstrated the strongest association with birth weight Z-score (adjusted β-coefficient = 0.43 [95%CI = 0.35; 0.50]). The area under curve (AUC) for predicting SGA was higher for sFlt-1/PlGF compared to sFlt-1 (0.74 versus 0.63, p = .006) and reached excellent prediction for SGA after preeclampsia (AUC 0.94). Optimal sFlt-1/PlGF ratio cut-offs had higher negative predictive value (NPV) and positive predictive value (PPV) for SGA (cut-off > 5.0; NPV = 99.1%, PPV = 5.4%) compared to each marker individually.Conclusion: The sFlt-1/PlGF ratio is a potential predictor of SGA in population-based screening, particularly when preeclampsia is also present.

An improved optimization algorithm of the three-compartment model with spillover and partial volume corrections for dynamic FDG PET images of small animal hearts in vivo

The three-compartment model with spillover (SP) and partial volume (PV) corrections has been widely used for noninvasive kinetic parameter studies of dynamic 2-[18F] fluoro-2deoxy-D-glucose (FDG) positron emission tomography images of small animal hearts in vivo. However, the approach still suffers from estimation uncertainty or slow convergence caused by the commonly used optimization algorithms. The aim of this study was to develop an improved optimization algorithm with better estimation performance. Femoral artery blood samples, image-derived input functions from heart ventricles and myocardial time–activity curves (TACs) were derived from data on 16 C57BL/6 mice obtained from the UCLA Mouse Quantitation Program. Parametric equations of the average myocardium and the blood pool TACs with SP and PV corrections in a three-compartment tracer kinetic model were formulated. A hybrid method integrating artificial immune-system and interior-reflective Newton methods were developed to solve the equations. Two penalty functions and one late time-point tail vein blood sample were used to constrain the objective function. The estimation accuracy of the method was validated by comparing results with experimental values using the errors in the areas under curves (AUCs) of the model corrected input function (MCIF) and the 18F-FDG influx constant Ki. Moreover, the elapsed time was used to measure the convergence speed. The overall AUC error of MCIF for the 16 mice averaged −1.4 ± 8.2%, with correlation coefficients of 0.9706. Similar results can be seen in the overall Ki error percentage, which was 0.4 ± 5.8% with a correlation coefficient of 0.9912. The t-test P value for both showed no significant difference. The mean and standard deviation of the MCIF AUC and Ki percentage errors have lower values compared to the previously published methods. The computation time of the hybrid method is also several times lower than using just a stochastic algorithm. The proposed method significantly improved the model estimation performance in terms of the accuracy of the MCIF and Ki, as well as the convergence speed.

G583(P) Improving interdisciplinary communication on a postnatal ward

Context Our hospital serves a surrounding population of over two hundred and fifty thousand people and caters to about three thousand deliveries a year. There is one postnatal ward with nineteen beds for mothers and their babies. It is usually staffed by three midwives, two healthcare assistants and one paediatric SHO during working hours. Problem Communication between the obstetric, midwifery and paediatric staff regarding any babies on the postnatal ward was casual and ad hoc with no set verbal or written handover between daytime and out of hours staff. This appeared to lead to delays in treatment of certain babies, for instance antibiotic administration, screening for sepsis and serum bilirubin measurements. Assessment of problem and analysis of its causes A multidisciplinary survey of those involved in obstetric and neonatal care was undertaken to identify the cause of these problems and to garner suggestions for improvement. Intervention A more formalised handover system was developed. Information was passed between the daytime paediatric SHO to the on call team using a printed handover sheet passed from the daytime paediatric SHO to the on call team. The sheet contains a list of babies needing specific paediatric input and includes aide memoires of NICE guidelines concerning early onset neonatal sepsis and neonatal jaundice. At change of shifts patients are discussed with the written sheet as a reminder. Study design This study was carried out as a clinical practice improvement project. Strategy for change The printed handover sheet was introduced on a Monday morning for a trial of four weeks. It was used at each morning, early evening and night-time handover. Its introduction followed discussion with the paediatric medical staff and the midwifery team via the ward sister. Measurement of improvement The staff of both departments were surveyed a month later to feed back any changes brought about through the new handover system. The results were very encouraging with 100% respondents reporting an improvement in communication of postnatal duties. Effects of changes There was a improvement in both the speed at which babies were reviewed and management plans instigated. The number of bleeps to the postnatal SHO decreased. No problems were encountered throughout the period of quality improvement. The midwifery staff are now considering introducing a similar system for their daily handover. Lessons learnt Importance of asking for feedback from all staff involved on the ward to obtain opinions on the need for change was the best way to do this. It has ensured any improvement introduced has been user friendly and staff are enthusiastic with regards to the change. If the authors were to repeat this quality improvement project, it would be useful to assess the implication of poor handover on infant care. For example missed/ late blood samples or delayed discharge. Message for others The message conveyed by this project is that every ward should have an effective handover and that with using simple measures dramatic differences can be made. This project identified a lack of effective handover on a postnatal ward which led to delayed or missed patient care. Using a handover tool designed following staff feedback, handover between staff members improved significantly and this positively impacted on patient care. Effective handover helps ensure patients receive appropriate and timely care. Potentially serious results are not forgotten about or missed when staff finish duty. It is essential as clinicians to ensure patients receive the best care and effective handover is an integral part of this.

Non-Negative Matrix Factorization Based Input Function Extraction for Mouse Imaging in Small Animal PET ? Comparison with Arterial Blood Sampling and Factor Analysis

Objectives: Retrieving the accurate time-tracer activity concentration curve of the blood (arterial input function) is mandatory for performing bio kinetic model analysis of dynamic PET data. Especially in small rodents, gathering the input function remains an active area of research as no generally applicable solution was found so far. While surgically catheterizing blood vessels of rodents is possible, it is labour intensive and time resolution of blood sampling is restricted due to the limited amount of overall blood and the procedure of blood withdrawal itself. Obtaining the input function from the PET images themselves seems thus to be favourable, but suffers from several factors, one of them being spill-in of adjacent tissues. Particularly in mice and for [18F]FDG, the spill-in complicates using the time-activity curve (TAC) from a region of interest (ROI) over the left ventricle (LV) because the signal of the ROI contains contributions from both, myocardial uptake as well as arterial blood activity. We propose non-negative matrix factorization (NMF) as an image based algorithm for separating myocardial tracer concentration from the blood input function. The aim of this study was to evaluate the potential of NMF as an image based algorithm for retrieving the input function by comparison with blood sampling and Factor Analysis (FA). Method: The femoral arteries of eight mice were surgically catheterized. With the injection of [18F]FDG, a 60 minute PET scan was started during which arterial blood samples were manually drawn from the catheter. For analysis, NMF and FA were performed in a ROI placed over the LV. The NMF algorithm shares similarities with principal component analysis and FA, the advantage over the later two being its non-negativity constraint. For normalization of the NMF extracted curve, the peak value of tracer activity in an early image of the LV and a late blood sample was used. The normalized NMF curve was visually compared to the TAC retrieved from the blood samples and to the FA retrieved TAC. For a quantitative comparison of performance, Pearson correlation and square-root of sum of squares (RSS) between NMF/FA and blood sampling curves was calculated. Results: TAC based on NMF, FA and arterial blood samples were obtained and compared in all 8 mice. The NMF derived curves described the blood sampling based curves visually significantly better than FA. Pearson correlation between NMF and blood sampling curves ranged from 0.21 to 0.92 with an average of 0.69. Pearson correlation for FA ranged from 0.46 to 0.81 with an average of 0.65. Mean RSS was 2.70E + 006 for NMF and 3.40E + 006 for FA. Conclusion: In the examined parameters, visual accordance, Pearson correlation and RSS, NMF performs superior to FA and seems to be a promising method for the extraction of the input function from PET images of small rodents without the need for arterial blood sampling.

Stress Management Skills and Reductions in Serum Cortisol Across the Year After Surgery for Non-Metastatic Breast Cancer

Treatment for breast cancer affects psychological adaptation and related neuroendocrine stress indicators. Previously, a 10-week cognitive behavioral stress management (CBSM) group intervention decreased cortisol over 12-months among women receiving treatment for breast cancer. The current re-analysis tested whether changes in stress management skills at 6-month follow-up predict the magnitude of cortisol reductions at 12-months in a time-lagged analysis. Women (N = 128) with non-metastatic breast cancer recruited post-surgery were randomized to the CBSM intervention or 1-day psychoeducational seminar. Participants reported perceived CBSM skills and provided late afternoon blood samples for serum cortisol at baseline and 6- and 12-month follow-ups. Improved perceived ability to relax and use cognitive reappraisal skills at 6-months statistically mediated intervention-associated cortisol reduction from 6- to 12-months. This is the first study showing that improved perceived CBSM skills predict the magnitude of cortisol reductions over 1 year in this population and may guide development of more focused interventions.

Avaliação do efeito da clorpromazina sobre a função renal de cães submetidos à isquemia e reperfusão

A isquemia renal está presente em diferentes situações como em cirurgias renais, vasculares e no transplante renal. O objetivo deste trabalho foi avaliar a integridade e a função renal de cães submetidos à isquemia e reperfusão com ou sem aplicação de clorpromazina. Para tanto foram utilizados 12 cães distribuídos aleatoriamente em dois grupos de seis indivíduos: grupo A com isquemia e reperfusão sem tratamento por clorpromazina e o grupo B com isquemia e reperfusão tratados previamente com clorpromazina. De cada cão foi coletado sangue e urina antes da isquemia, no inicio da reperfusão, após 120 minutos de reperfusão e semanalmente até 28º dia pós-cirúrgico para verificar possíveis efeitos tardios da isquemia/reperfusão. Avaliações da integridade e função renal foram feitas por exame físico, concentração sérica de ureia e creatinina e determinação da GGT urinária. A avaliação da relação proteína urinária/creatinina urinária (PU/CU) e atividade da GGT urinária são exames mais sensíveis para detectar lesão tubular aguda que o exame de urina de rotina, uma vez que estas variáveis apresentaram alteração mais precocemente. Não houve ação protetora da clorpromazina conforme constatado por meio da urinálise, dosagens séricas de ureia e creatinina, excreção urinária de GGT e PU/CU.

Spillover and Partial-Volume Correction for Image-Derived Input Functions for Small-Animal 18F-FDG PET Studies

We present and validate a method to obtain an input function from dynamic image data and 0 or 1 blood sample for small-animal 18F-FDG PET studies. The method accounts for spillover and partial-volume effects via a physiologic model to yield a model-corrected input function (MCIF). Image-derived input functions (IDIFs) from heart ventricles and myocardial time-activity curves were obtained from 14 Sprague-Dawley rats and 17 C57BL/6 mice. Each MCIF was expressed as a mathematic equation with 7 parameters, which were estimated simultaneously with the myocardial model parameters by fitting the IDIFs and myocardium curves to a dual-output compartment model. Zero or 1 late blood sample was used in the simultaneous estimation. MCIF was validated by comparison with input measured from blood samples. Validation included computing errors in the areas under the curves (AUCs) and in the 18F-FDG influx constant Ki in 3 types of tissue. For the rat data, the AUC error was 5.3% +/- 19.0% in the 0-sample MCIF and -2.3% +/- 14.8% in the 1-sample MCIF. When the MCIF was used to calculate the Ki of the myocardium, brain, and muscle, the overall errors were -6.3% +/- 27.0% in the 0-sample method (correlation coefficient r = 0.967) and 3.1% +/- 20.6% in the 1-sample method (r = 0.970). The t test failed to detect a significant difference (P > 0.05) in the Ki estimates from both the 0-sample and the 1-sample MCIF. For the mouse data, AUC errors were 4.3% +/- 25.5% in the 0-sample MCIF and -1.7% +/- 20.9% in the 1-sample MCIF. Ki errors averaged -8.0% +/- 27.6% for the 0-sample method (r = 0.955) and -2.8% +/- 22.7% for the 1-sample method (r = 0.971). The t test detected significant differences in the brain and muscle in the Ki for the 0-sample method but no significant differences with the 1-sample method. In both rat and mouse, 0-sample and 1-sample MCIFs both showed at least a 10-fold reduction in AUC and Ki errors compared with uncorrected IDIFs. MCIF provides a reliable, noninvasive estimate of the input function that can be used to accurately quantify the glucose metabolic rate in small-animal 18F-FDG PET studies.

Persistent elevation of plasma vascular endothelial growth factor levels during the first month after minimally invasive colorectal resection

Elevations of plasma vascular endothelial growth factor (VEGF) have been noted early after colorectal resection. The duration of this increase is unknown. Because VEGF is a potent promoter of angiogenesis, which is critical to tumor growth, a sustained increase in blood VEGF levels after surgery may stimulate the growth of residual metastases early after surgery. This preliminary study aimed to determine VEGF levels during the first month after colorectal resection. Patients from three prospective studies that had late postoperative blood samples available comprised the study population. Demographic, perioperative, pathologic, and complication data were collected. Plasma samples were obtained preoperatively for all patients: on postoperative day (POD) 1 for most patients and at varying time points thereafter during the first month after surgery and beyond. Levels of VEGF were determined via enzyme-linked immunoassay (ELISA) and compared using Wilcoxon's matched pairs test. Because the numbers of specimens beyond POD 5 were limited, samples from 7-day time blocks were bundled and averaged to permit statistical analysis. A total of 49 patients with cancer and 30 patients with benign indications, all of whom underwent minimally invasive colorectal resection, were assessed separately. With regard to the patients with cancer, the median preoperative plasma value was 150 pg/ml, and the peak postoperative median value for the POD 14 to 20 time block was 611.1 pg/ml. Furthermore, compared with the preoperative results, significant VEGF elevations were noted on POD 3 as well as during week 2 (POD 7-13), week 3 (POD 14-20), and week 4 (POD 21-27) (p < 0.05 for each). With regard to the benign patients, the median preoperative VEGF level was 112 pg/ml, and the peak postoperative value, 286 pg/ml, was noted during postoperative week 2. Significant elevations were noted on POD 3, and for weeks 2 and 3 as well as for POD 28 and later. Between 63% and 89% of the patients at each time point beyond POD 5 had elevated VEGF levels. This preliminary study demonstrates that after minimally invasive colorectal resection for cancer, median VEGF levels are significantly elevated on POD 3 and remain increased for as long as 4 weeks. Significant elevations in a similar pattern also were noted for the benign patients. However, the baseline and postoperative median values were lower. The clinical impact from increased blood levels of VEGF is uncertain. It is possible that the growth of residual tumor deposits may be stimulated early after surgery. These results warrant a larger study as well as endothelial cell in vitro assays to determine whether postoperative plasma stimulates proliferation and invasion.

Comparison of SUV and Patlak slope for monitoring of cancer therapy using serial PET scans.

The standardized uptake value (SUV) and the slope of the Patlak plot ( K) have both been proposed as indices to monitor the progress of disease during cancer therapy. Although a good correlation has been reported between SUV and K, they are not equivalent, and may not be equally affected by metabolic changes occurring during disease progression or therapy. We wished to compare changes in tumor SUV with changes in K during serial positron emission tomography (PET) scans for monitoring therapy. Thirteen patients enrolled in a protocol to treat renal cell carcinoma metastases were studied. Serial dynamic fluorodeoxyglucose (FDG) PET scans and computed tomography (CT) and magnetic resonance (MR) scans were performed once prior to treatment, once at 36+/-2 days after the start of treatment, and (in 7/13 subjects, 16/27 lesions) a third time at 92+/-9 days after the start of treatment. This resulted in a total of 33 scans, and 70 tumor Patlak and SUV values (one value for each lesion at each time point). SUV and K were measured over one to four predefined tumors/patient at each time point. The input function was obtained from regions of interest over the heart, combined, if necessary, with late blood samples. Over all tumors and scans, SUV and K correlated well ( r=0.97, P<0.0001). However, change in SUV with treatment over all tumor scan pairs was much less well correlated with the corresponding change in K ( r=0.73, P<0.0001). The absolute difference in % change was outside the 95% confidence limits expected from previous variability studies in 6 of 43 pairs of tumor scans, and greater than 50% in 2 of 43 tumor scan pairs. In four of the six cases, the two indices predicted opposing therapeutic outcomes. Similar results were obtained for SUV normalized by body weight or body surface area and for SUVs using mean or maximum count. Changes in CT and MR tumor cross-product dimensions correlated poorly with each other ( r=0.47, P=NS), and so could not be used to determine the "correct" PET index. Absolute values of SUV and K correlated well over the patient population. However, when monitoring individual patient therapy serially, large differences in the % changes in the two indices were occasionally found, sometimes sufficient to produce opposing conclusions regarding the progression of disease.

The effect of dexamethasone administration at different stages of gestation on maternal plasma steroid concentrations in the baboon (Papio cynocephalus).

Dexamethasone administration at different stages of gestation in the baboon was studied for its effect on maternal steroid hormone concentrations. Dexamethasone (2 mg i.m. at 12 h intervals for three doses) was administered at early (days 37-39), mid (days 76-85) or late (days 112-123) gestation and morning blood samples were collected before, during and after dexamethasone suppression for 6 consecutive days. Dexamethasone treatment, at all stages of pregnancy, resulted in a significant decline in maternal serum cortisol concentrations, which rapidly return to normal concentrations after treatment. Progesterone concentrations were not affected by dexamethasone at any stage of gestation. Serum concentrations of oestradiol, testosterone and androstenedione were unchanged following dexamethasone administration in early pregnancy. A trend toward lower serum oestradiol was observed following dexamethasone administration in both mid and late gestation, but this was not significant. Both testosterone and androstenedione were significantly decreased following dexamethasone in both mid and late pregnancy and recovered to pretreatment concentrations within a few days after cessation of treatment. These results confirm other studies which demonstrate that adrenal precursors (maternal or fetal) are a major contributor to maternal serum concentrations of oestradiol. They also demonstrate that these adrenal precursors increase serum concentrations of testosterone and androstenedione in the pregnant baboon. Since these changes are only evident after that time (>40 days) when the fetal adrenal is steroidogenically competent, a role for fetal adrenal involvement in maternal serum androgen concentrations is suggested.

Smoking during pregnancy: how reliable are maternal self reports in New Zealand?

OBJECTIVE: To determine the reliability of self reports of smoking during pregnancy. METHODS: Residual sera from early and late antenatal blood samples were tested for cotinine for all pregnancies over...

Prospective study of blood culture during transesophageal echocardiography

To ascertain the incidence and significance of bacteremia associated with transesophageal echocardiography (TEE), 132 consecutive patients (aged 17 to 73 years) free of apparent infection who were undergoing 135 transesophageal echocardiographic procedures from October 1990 to August 1991, were prospectively studied. For each procedure, two sets of blood cultures were obtained for culture 30 to 60 minutes before TEE, immediately after, and 180 to 240 minutes after the procedure. For each blood culture, 10 ml of venous blood was evenly inoculated into aerobic and anaerobic culture bottles and inoculated for 7 days using a radiometric system. A throat swab was obtained immediately before each procedure. Three of 270 preprocedure blood cultures were positive for Bacillus cereus, Staphylococcus simulans, and Peptostreptococcus species, respectively. No blood culture was positive in the immediate postprocedure period. Two of 270 late blood samples grew Staphylococcus epidermidis in the same patient. Nevertheless, the microorganisms isolated from blood cultures were different from those isolated from the throat swab. No patients had fever or evidence of infective endocarditis after TEE during the follow-up period. It is concluded that the incidence of TEE-related bacteremia is extremely low, and a general recommendation for antibiotic prophylaxis during TEE is not warranted.

Cord blood platelet aggregation; quality control by a two-sample technique.

Two blood samples were taken from the cords at 17 normal deliveries 2-4 min and 5-8 min after birth, respectively. The difference in platelet count between early and late samples in platelet-rich plasma was less than 5% in nine cords (Group A), and greater in eight cords (Group B). Platelet aggregation studies on the early and the late blood samples showed consistent results within each cord in Group A but not in Group B. The correlations between the responses were high for Group A. The aggregation responses were also slightly but significantly higher in the late samples in this group (p less than 0.01 in Group A; n.s. in Group B). The differences between responses in early and late blood samples could not be explained by acid-base dissimilarities. The variability in cord blood platelet aggregation results can be greatly reduced by platelet counting in PRP of two independent blood samples, accepting only samples with concordant platelet counts (less than 5% difference).

A gamma camera method for quantitation of split renal function in children followed for vesicoureteric reflux.

A method for quantitative estimation of split renal function using a computerized gamma camera system is described. 42 children and adolescents with existing or preexisting vesicoureteric reflux and recurrent urinary tract infection were investigated. Total renal clearance of DTPA was calculated with a disappearance curve derived from the largest extrarenal area in the field of view of a gamma camera with diverging collimator. Split renal function was estimated with the slopes of second phase renograms. The plasma disappearance clearance of DTPA, calculated using one compartment model with two late blood samples, gave similar results with the clearance estimated from the body disappearance curves. The proportional planimetric renal parenchymal areas had good correlation with the split clearance estimated from renogram slopes. The method offers data on renal function and urinary tract dynamics which is very valuable in the follow-up of children with recurrent urinary tract infection and vesicoureteric reflux.

EVALUATION OF A MEASLES-SMALLPOX VACCINATION CAMPAIGN BY A SERO-EPIDEMIOLOGIC METHOD1

An assessment technique has been devised whereby children from 30 randomly chosen sampling sites are visited within three days of measles-smallpox vaccination and one month later. Vaccination coverage is measured at house visits and immunologic status is determined by collection of early and late blood samples on filter papers from substratified children in priority age-groups, and by looking at vaccination scars. The methodology was employed in a rural area of the Ivory Coast during the maintenance phase of a measles-smallpox vaccination program; 1762 children from 0--72 months old were inspected. Children in the target age groups, 6--24 months, had a vaccination coverage of 53.6% whereas children outside of the target group had a 10.5% coverage. Of 571 target age children, 94.6% had a measles hemagglutination-inhibition antibody titer of less than 1:10 dilution at the first visit, and were presumed susceptible to measles or vaccine. Of 247 substratified children 6--8 months, 98.3% were susceptible to measles before vaccination; 84.3% of 127 vaccinated children in this age-group sero-converted when re-tested. Of 324 children 9--24 months, 91.7% were susceptible before the campaign; 94.7% of 170 vaccinated children in this age-group converted. A positive history of prior measles or prior measles-vaccination was not a good indicator of measles serologic status. The smallpox vaccination major reaction rate was 93.2%; 91.4% of children with a recent vaccination scar sero-converted to measles vaccine. Thus, the smallpox scar read at the second visit proved the best clinical marker for determining both coverage and immunologic effectiveness of the campaign.