Platelet response to aspirin and clopidogrel in patients with peripheral atherosclerosis

Aspirin and clopidogrel are important drugs in the secondary prevention of ischemic events. A considerable individual variation in platelet response to these drugs has, however, been reported, and high residual platelet reactivity despite treatment may be an independent risk factor for ischemic events. Most studies have been undertaken in patients with coronary heart disease, but patients with peripheral artery disease (PAD) may exhibit greater residual platelet reactivity, possibly because of platelet activation by a larger area of diseased endothelium. It is yet unsettled which method that best measures platelet reactivity and an eventual lack of response to aspirin. Several instruments are promoted to measure platelet response and low-response to platelet inhibitors, but it is questionable if they measure this in comparable ways. We studied the comparability of three tests of platelet reactivity for the assessment of low-response to aspirin and clopidogrel in patients with PAD. In 263 patients, platelet function was assessed twice, 3 months apart, by the Platelet Function Analyzer-100 (PFA), light transmission aggregometry (LTA), and whole blood impedance aggregometry (IA). In a subgroup of 43 patients, we studied the effect of a single dose of 600 mg clopidogrel on platelet function. Low-response to aspirin assessed by analyses targeting cyclooxygenase-1 activity (LTA, IA) was rare (≤ 8.1%). With the PFA, we found 17% with low response at both visits, and 60% who were consistently responsive, whereas 23% were categorized differently at the two visits. Low response to clopidogrel, occurred in 0-23%, depending on the method and the criteria used. A low-response to aspirin, defined by lack of COX-1 inhibition, is a rare phenomenon whereas high residual platelet reactivity as determined by PFA may be a rather frequent finding but is not consistent over time in all patients. A low-response to clopidogrel depends very much on the method and definition used.     

Impaired reproductive development in sons of women occupationally exposed to pesticides during pregnancy

Objectives

The aim of this prospective study was to investigate whether occupational pesticide exposure during pregnancy causes adverse effects on the reproductive development in the male infants.

Design and measurements

Pregnant women employed in greenhouses in Denmark were consecutively recruited, and 113 mother–son pairs were included. The mothers were categorized as occupationally exposed (91 sons) or unexposed (22 sons) to pesticides during pregnancy. Testicular position and volume, penile length, and position of urethral opening were determined at 3 months of age using standardized techniques. Concentrations of reproductive hormones in serum from the boys were analyzed.

Results

The prevalence of cryptorchidism at 3 months of age was 6.2% [95% confidence interval (CI), 3.0–12.4]. This prevalence was considerably higher than among Danish boys born in the Copenhagen area (1.9%; 95% CI, 1.2–3.0) examined by the same procedure. Boys of pesticide-exposed mothers showed decreased penile length, testicular volume, serum concentrations of testosterone, and inhibin B. Serum concentrations of sex hormone-binding globulin, follicle-stimulating hormone, and the luteinizing hormone:testosterone ratio were increased compared with boys of nonexposed mothers. For individual parameters, only the decreased penile length was statistically significant (p = 0.04). However, all observed effects were in the anticipated direction, and a joint multivariate test showed that this finding had a p-value of 0.012.

Conclusions

Our findings suggest an adverse effect of maternal occupational pesticide exposure on reproductive development in the sons despite current greenhouse safeguards and special measures to protect pregnant women.     

Regional changes in brain perfusion during brain maturation measured non-invasively with Arterial Spin Labeling MRI in neonates

Purpose

The purpose of this study was to evaluate if non-invasive Arterial Spin Labeling MR imaging can be used to assess changes in brain perfusion with age which reflect neonatal brain development. For this purpose regional perfusion values obtained with ASL MR imaging were evaluated as a function of postmenstrual age.

Materials and methods

Pulsed ASL imaging was performed in 33 neonates with a postmenstrual age from 30 to 53 weeks. Whole brain cerebral blood flow (wbCBF), CBF in the basal ganglia and thalamus (BGT-CBF), in the occipital cortex (OC-CBF) and the frontal cortex (FC-CBF) were measured. Regional CBF values were expressed quantitatively (in ml/100 g min) and relative as a percentage of the wbCBF.

Results

Mean wbCBF increased significantly from 7 ± 2 ml/100 g min (mean ± sd) at 31 ± 2 weeks postmenstrual age to 12 ± 3 ml/100 g min at term-equivalent age (TEA) and 29 ± 9 ml/100 g min at 52 ± 1 weeks postmenstrual age. Relative regional CBF was highest in the BGT at all time-points. Relative OC-and FC-CBF increased significantly from 31 ± 2 weeks postmentrual age to TEA. A significant difference in relative BGT-CBF and OC-CBF was shown between infants at 31 ± 2 weeks postmenstrual age and infants scanned at 52 ± 1 weeks postmenstrual age. Relative perfusion in the BGT measured at TEA was significant different compared to 52 ± 1 weeks postmenstrual age.

Conclusion

In conclusion, regional differences in CBF and changes with postmenstrual age could be detected with ASL in neonates. This suggests that ASL can be used as a non-invasive tool to investigate brain maturation in neonates.     

Required time delay from <Superscript>99m</Superscript>Tc-HMPAO injection to SPECT data acquisition: healthy subjects and patients with rCBF pattern

Purpose  Functional brain ^99mTc-HMPAO single-photon emission computed tomography (SPECT) is a useful diagnostic tool for assessment of regional cerebral blood flow, particularly in dementia, cerebrovascular disease and epilepsy. Currently, the European and American Association of Nuclear Medicine Procedure Guidelines for Brain Perfusion SPET using ^99mTc-labeled Radiopharmaceuticals recommend a time delay of 90 min between injection of ^99mTc-HMPAO and data acquisition. This time delay is difficult to comply within the daily routine and present a problem, particularly with the elderly or demented patients. This study investigates in patients with perfusion deficits and in healthy subjects if the quality of the SPECT image is affected by lowering the time delay between ^99mTc-HMPAO injection and data acquisition to 30 or 60 min. Methods  Thirty-seven healthy subjects (17 females; mean age 65; range 42–84 years) with normal cerebral blood flow distribution and 31 patients (17 females; mean age 67; range 38–84) with reduced rCBF distribution were included. Images were obtained with a three-headed Philips IRIX SPECT scanner with high-resolution collimators. The healthy subjects were scanned 30, 60 and 90 min after ^99mTc-HMPAO injection, and the patients were scanned 30 and 90 or 60 and 90 min after ^99mTc-HMPAO injection. For evaluation of differences between the images obtained at various time points after injection, two different methods were used. The z-map method was used to subtract images from each other prior to visual inspection. In addition, principal component analysis was used as a quantitative analysis of the similarity of the images. Results  Visual inspection of the subtracted images (30 or 60 versus 90 min) revealed that there was no spatial bias. Quantitatively, the average proportion of the total variance explained by the first principal component was 99.5% (range 98.9–99.6) for the healthy subjects and 99.4% (range 98.5–99.8) for the patients. Conclusion  The time delay from injection of ^99mTc-HMPAO to the start of the SPECT data acquisition can be reduced from 90 to 30 min without any significant impact on the quality of the acquired image.