Residue Levels of Organochlorine Pesticides in Breast Milk and Its Associations with Cord Blood Thyroid Hormones and the Offspring's Neurodevelopment.

Previous studies have demonstrated that organochlorine pesticide (OCP) exposure has a negative impact on the neurological function of infants. Only a few reports have investigated the thyroid and growth hormones and their relationship to neurodevelopment after human exposure to OCPs, especially in the case of infants. Our goal was to determine whether breastmilk OCP residues were associated with negative impacts and/or alterations in the neurodevelopment of infants among specific southern Taiwanese mother-breastfed infant pairs. Our subjects (n = 55 pairs) were recruited from southern Taiwan between 2007 and 2010. The thyroid and growth hormone levels in the cord blood samples collected after childbirth were determined. The breastmilk was gathered within one month after childbirth for the determination of OCP levels using a high-resolution gas chromatograph with mass spectrometry, and the neurodevelopment of 10-12-month-old infants was examined using the Bayley Scales of Infant and Toddler Development®, Third Edition (Bayley-III). It was observed that 4,4'-dichlorodiphenyl-dichloroethylene (4,4'-DDE) (mean = 10.3 ng/g lipid) was the most predominant OCP compound in the breastmilk samples. At higher concentrations (>75th percentile), specific OCPs were associated with significantly lower levels of thyroid and growth hormones than at lower concentrations (<75th percentile). Significantly higher odds ratios (ORs) were observed for binary cognitive (OR = 8.09, p = 0.025 for 4,4'-DDT), language (OR = 11.9, p = 0.013 for 4,4'-DDT) and social-emotional (OR = 6.06, p = 0.01 for trans-CHL) composite scores for specific OCPs belonging to the lower exposure group as compared to the higher OCP exposure group. The five domain Bayley-III infant neurodevelopment outcomes were negatively associated with specific OCPs in the breast milk samples based on the redundancy analysis (RDA) test. Bayley-III scales, which include cognitive, language, motor, social-emotional, and adaptive behavior scales, could be predicted by 4,4'-DDT, endrin, endosulfan I, heptachlor, or heptachlor epoxide using multivariate linear regression models with adjustment for maternal age, pre-pregnant BMI, parity, and infant gender. In conclusion, although our study showed that postnatal exposure to breast milk OCPs may be associated with infant neurodevelopmental outcomes and that prenatal exposure, if extrapolated from breastmilk levels, is associated with changes in thyroid and growth hormones that may have effects on neurodevelopment, these associations are only suggestive; thus, further studies are recommended for confirmation.

Transfemoral Venous Access Facilitates Upper Extremity Dialysis Interventions: Procedural Success and Clinical Outcomes.

PURPOSE: To report technical success and clinical outcomes of transfemoral venous access for upper extremity dialysis interventions. MATERIALS AND METHODS: A total of 15 patients underwent a transfemoral venous approach for fistulography (n = 4; 27%) or thrombectomy (n = 11; 73%) over a 14-month period. Access characteristics, sheath size, thrombectomy method, angioplasty site, fluoroscopy time, radiation dose, technical and clinical success, complications, and post-intervention primary and secondary patency rates were recorded. RESULTS: Access type included arteriovenous fistulas (n = 10; 67%) and grafts (n = 5; 33%). The most common configuration was brachio-brachial (n = 6; 38%). Mean age of access was 37 months. Mean prior interventions were 4. Right CFV access was used in all patients using 6-8-French (most common: 7-French [n = 10; 67%]) sheaths. Most thrombectomies (n = 11; 73%) required both pharmacologic and mechanical maceration (n = 9; 82%). All accesses required angioplasty to treat underlying stenosis at the outflow vein (n = 12; 80%) or arteriovenous anastomosis (n = 9; 90%). Mean fluoroscopy time was 26.43 min. Air kerma and dose area product were 178.06 ± 225.77 mGy and 57,768.83 ± 87,553.29 µGym2, respectively. Procedural and clinical success rates were 93% and 80%, respectively. Technical failure was due to persistent stenosis in one patient. Clinical failure was due to unsuccessful dialysis immediately following intervention in three patients. Mean post-intervention primary patency and secondary patency durations were 2.8 and 4.8 months, respectively. Primary patency rates at 1 and 3 months were 50% and 35%, respectively. Secondary patency rates at 1 and 3 months were 58% and 30%, respectively. CONCLUSION: A transfemoral venous approach for intervention of upper extremity dialysis accesses may be a valuable adjunct to traditional approaches.

Cerebral vasospasm patterns following aneurysmal subarachnoid hemorrhage: an angiographic study comparing coils with clips.

BACKGROUND AND PURPOSE: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) results in significant morbidity due to ischemia. Subarachnoid hematoma evacuation during aneurysm clipping reduces the incidence of vasospasm. However, studies comparing endovascular coiling with open clipping have reported similar rates of spasm. We addressed the question of how coiling produces similar (if not less) vasospasm without the benefit of clot evacuation by evaluating vasospasm patterns among patients with aSAH. We hypothesize that cerebrospinal fluid (CSF) circulation plays a major role in clearing blood breakdown products, and that coiling may preserve CSF flow in the subarachnoid space. METHODS: A retrospective chart review identified 36 (18 coiled/18 clipped) patients with aSAH who developed angiographic vasospasm. The degree of spasm was quantified using an ordinal scale from 0 (none) to 5 (severe) for 26 anatomic vessel segments evaluated on 164 successive angiograms. Statistical analysis was performed using the Fisher exact test for proportions and the Wilcoxon and Student t tests on ordinal/continuous measures. Quadratic regression was also used as a model for spasm activity versus post-bleed days. RESULTS: In both the coiling and clipping groups the most severely spastic vessels were located adjacent to aneurysm rupture. Perianeurysmal spasm affected all subjects. However, whereas spasm remained largely confined in patients treated by clipping, those who underwent coiling developed stepwise progression distally over time. The distal vasospasm severity scores were higher among subjects treated by coiling, particularly in the most dependent regions of the subarachnoid space. CONCLUSIONS: Patients with aSAH treated by endovascular coiling and surgical clipping demonstrate distinct vasospasm patterns. While both initially exhibit perianeurysmal spasm, patients treated by coiling go on to develop stepwise progression distally over time. This finding may reflect dispersion of blood breakdown products along preserved CSF egress pathways in patients treated by endovascular coiling.

Morphologic and hemodynamic risk factors in ruptured aneurysms imaged before and after rupture.

BACKGROUND AND PURPOSE: Due to limited information about aneurysm natural history, choosing the appropriate management strategy for an unruptured aneurysm is challenging. By comparing unruptured and ruptured cases, studies have identified a variety of aneurysm morphologic and hemodynamic properties as risk factors for rupture. In this study, we investigated changes in 4 ruptured aneurysms before and after rupture and tested whether previously published risk factors identified a risk before rupture. MATERIALS AND METHODS: A retrospective review of ruptured aneurysms based on the inclusion criteria of documenting angiographic images before and after rupture was performed. Such cases are extremely rare. To minimize hemodynamic influence due to location, we selected 4 cases at the posterior communicating artery. 3D morphologic and hemodynamic analyses were applied to examine qualitative and quantitative risk factors in aneurysms before and after rupture. RESULTS: When we compared aneurysms before and after rupture, all increased in size. Volume, surface area, and morphology changed in both high and low wall shear stress areas. Aneurysm surface ratio, nonsphericity index, and pulsatility index were the only risk factors to consistently identify risk before and after aneurysm rupture for all aneurysms. CONCLUSIONS: Although changes in shape and flow properties were found before and after aneurysm rupture, in this small study, we found that some risk factors were evident as early as 2 years before rupture.

Comprehensive low-dose imaging of carotid and coronary arteries with a single-injection dual-source CT angiography protocol.

AIM: To assess the feasibility of a fast single-bolus combined carotid and coronary computed tomography angiography (CTA) protocol in asymptomatic patients. MATERIALS AND METHODS: Thirty-three consecutive patients (18 women and 15 men) with a median age of 61 ± 14 years old (range 37-87 years) with known or suspected atherosclerotic disease were enrolled in this prospective study. A single breath-hold, single biphasic injection protocol (50 ml at 3 ml/s, 50 ml at 5 ml/s, 50 ml saline flush at 5 ml/s) was used for combined CTA imaging of the supra-aortic (SAA) and coronary arteries (CA) on a 64-slice dual-source CT (DSCT) machine. Helical CTA acquisition of the SAA was followed by prospective electrocardiography (ECG)-triggered coronary CTA. Subjective (four-point scale) image quality and objective signal-to-noise (SNR) and contrast-to-noise (CNR) measurements were performed. Vascular disease was graded on a four-point scale (grade 1: absent; grade 2: mild, grade 3: moderate; grade 4: severe). The radiation dose was recorded for each patient. RESULTS: The average enhancement and subjective quality score of SAA and CA segments were 396 HU/358 HU and 1.2 ± 0.3/1.72 ± 0.4, respectively. The SNR was 27.1 ± 1.7 in the SAA and 21.6 ± 1.6 in the CA (p < 0.0001). The CNR was 18.1 ± 1.2 and 15.9 ± 1.8, respectively (p = 0.4). Four percent of SAA and 14% of CA segments (mostly due to peri-venous streak artefacts and small calibre, respectively) produced non-diagnostic images. SAA findings were as follows: 26/33 (79%) patients showed no disease and 6/33 (18%) had grade 2 and 1/33 (3%) had grade 3 disease. CA findings were as follows: 25/33 (76%) showed no disease and 6/33 (18%) patients had grade 2 and 2/33 (6%) had grade 3 disease. Five patients had disease in both districts. The average radiation dose for the combined CTA angiogram was 4.3 ± 0.6 mSv. CONCLUSION: A fast, low-dose combined DSCT angiography protocol appears technically feasible for imaging carotid and coronary atherosclerotic disease.

Cardiac dual-source CT for the preoperative assessment of patients undergoing bariatric surgery.

AIM: To assess the diagnostic value of coronary dual-source computed tomography (DSCT) as a comprehensive, non-invasive tool in the preoperative cardiac evaluation of patients undergoing bariatric surgery. MATERIALS AND METHODS: Thirty consecutive obese [average body mass index (BMI): 45 ± 7.6, range: 35-59] patients (24 women; six men; median age: 52 ± 15 years) were enrolled in this institutional review board (IRB)-approved, Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant prospective study. Calcium scoring (CaS) and electrocardiography (ECG)-gated images of the coronary arteries were obtained with a large body habitus protocol (120 kV; 430 mAs; 100 ml iodinated contrast medium at 7 ml/s injection rate) on a DSCT machine. Qualitative (four-point: 1 = excellent to 4 = not delineable) coronary segmental analysis, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) measurements were performed. The presence and degree of vascular disease (four-grade scale: mild to severe) was correlated with CaS and cardiovascular (CV) risk stratification blood tests. In patients with severe stenosis (>70%), findings were compared with cardiac nuclear medicine imaging (single photon-emission computed tomography; SPECT) imaging. RESULTS: The average HR, enhancement, and quality score were 64 ± 7 beats/min, 288 ± 66 HU and 1.8 ± .5, respectively. Ninety-three percent (417/450) of the coronary segments were rated diagnostic. The SNRs and CNRs were 17 ± 9 and 12 ± 7 for the right coronary artery; 17 ± 8 and 12 ± 7 for the left main coronary artery; 16 ± 9 and 11 ± 7 for the left anterior descending coronary artery; and 15 ± 7 and 10 ± 6 for the left circumflex coronary artery. Ten of the 30 patients (33%) demonstrated coronary artery disease (CAD) of which two (6%) showed three-vessel disease. Four (13%) patients showed severe disease: in three of which the presence of significant stenosis was confirmed by SPECT and by catheter angiography in the fourth patient. Neither the CaS, nor the CV risk stratification tests showed significant correlation with presence or degree of CAD (p > 0.05). CONCLUSIONS: Coronary DSCT is a robust alternative imaging tool in the preoperative assessment of patients undergoing bariatric surgery.

The impact of thromboemboli histology on the performance of a mechanical thrombectomy device.

BACKGROUND AND PURPOSE: Recently we published a novel method of thrombus preparation for use in a swine model for evaluation of thrombectomy designs. The clot (fibrin rich clot) is characterized by its similarity in histologic characteristics to the thromboemboli recovered from stroke patients. The purpose of this latest study was to evaluate if the performance of a mechanical thrombectomy device was affected by the histologic characteristics of thromboembolus. Erythrocyte rich clot, which was created using exogenous thrombin, and the novel experimental clot with abundance of fibrin/cellular component were used for comparison. The Merci clot retriever was used for the evaluation and the angiographic outcomes were analyzed. MATERIALS AND METHODS: Two histologically different types of experimental clot, a conventionally used thrombin-induced clot (erythrocyte-rich clot) and a novel experimental clot that is similar in histologic characteristics to the thromboemboli recovered from patients with stroke (fibrin-rich clot), were prepared. Eight extracranial arteries in swine were occluded with erythrocyte-rich clot (group A), and 8 were occluded with fibrin-rich clot (group B), and MT by using the Merci clot retriever device was performed. Angiographic results in each group were evaluated. RESULTS: A total of 48 attempts at MT were made. The average number of attempts to achieve TIMI grade II or III recanalization was 2.75 times in group A and 4.5 times in group B (P < .001), respectively. The mean time to achieve recanalization was 15.5 minutes in group A and 81.5 minutes in group B (P < .01). Every vessel in group A showed recanalization (100%), whereas only 3 of 8 samples (37.5%) achieved recanalization in group B. CONCLUSIONS: In this model, arteries occluded by fibrin-rich clot demonstrated a significantly lower recanalization rate, lower final TIMI score, and a longer mean recanalization time than did arteries occluded by erythrocyte-rich clot. The angiographic outcome of MT by using the Merci clot retriever system was influenced by the histologic characteristics of the occluding thromboembolus.

3D quantitative evaluation of atherosclerotic plaque based on rotational angiography.

BACKGROUND AND PURPOSE: Atherosclerosis is a systemic disease that has been shown to cause various cardiovascular diseases and stroke. However, technologies to evaluate the volume of atherosclerotic plaque are limited. We present a method for determination of 3D plaque volume based on RA. MATERIALS AND METHODS: 3DRA images obtained from patients were used to evaluate the plaque. Six patients who were diagnosed with atherosclerotic lesions were included. The PR model developed for 3DRA was applied to analyze the geometry of the vessel and calculate the plaque volume. To validate the present method, we tested computer-generated phantoms with different degrees of stenosis. RESULTS: Application of PR to clinical cases allowed the estimation of plaque morphology and quantification of plaque volume. Technique validation showed that on average, PR can rebuild 92% of the plaque and provide satisfactory determination of plaque volume. CONCLUSIONS: A new approach to obtain plaque volume based on 3DRA is presented. The initial tests in 6 clinical cases and validation with different phantoms showed that this method is feasible. Further validation in a larger clinical series is required to assess the ultimate value of the present technique.

Quantitative hemodynamic analysis of brain aneurysms at different locations.

BACKGROUND AND PURPOSE: Studies have shown that the occurrence of brain aneurysms and risk of rupture vary between locations. However, the reason that aneurysms at different branches of the cerebral arteries have different clinical presentations is not clear. Because research has indicated that aneurysm hemodynamics may be one of the important factors related to aneurysm growth and rupture, our aim was to analyze and compare the flow parameters in aneurysms at different locations. MATERIALS AND METHODS: A total of 24 patient-specific aneurysm models were constructed by using 3D rotational angiographic data for the hemodynamic simulation. Previously developed computational fluid dynamics software was applied to each aneurysm to simulate the blood-flow properties. Hemodynamic data at peak pulsatile flow were recorded, and wall shear stress (WSS) and flow rate in the aneurysms and parent arteries were quantitatively compared. To validate our method, a comparison with a previously reported technique was also performed. RESULTS: WSS and flow rate in the aneurysms at the peak of the cardiac cycle were found to differ in magnitude between different locations. Multiple comparisons among locations showed higher WSS and flow rate in middle cerebral artery aneurysms and lower WSS and flow rate in basilar artery and anterior communicating artery aneurysms. CONCLUSIONS: We observed changes in hemodynamic values that may be related to aneurysm location. Further study of aneurysm locations with a large number of cases is needed to test this hypothesis.

The indirect alloresponse impairs the induction but not maintenance of tolerance to MHC class I-disparate allografts.

We studied the effects of indirect allorecognition on the induction and maintenance phases of tolerance in miniature swine cotransplanted with heart and kidney allografts. MHC class I-mismatched heart and kidney grafts were cotransplanted in recipients receiving CyA for 12 days. Recipients were unimmunized or immunized with a set of donor-derived or control third-party MHC class I peptides either 21 days prior to transplantation or over 100 days after transplantation. T-cell proliferation, delayed type hypersensitivity reaction (DTH) and antibody production were assessed. All animals injected with donor MHC class I peptides developed potent indirect alloresponses specific to the immunizing peptides. While untreated recipients developed stable tolerance, all animals preimmunized with donor allopeptides rejected kidney-heart transplants acutely. In contrast, when peptide immunization was delayed until over 100 days after kidney-heart transplantation, no effects were observed on graft function or in vitro measures of alloimmunity. Donor peptide immunization prevented tolerance when administered to recipients pre transplantation but did not abrogate tolerance when administered to long-term survivors post transplantation. This suggests that the presence of T cells activated via indirect allorecognition represent a barrier to the induction but not the maintenance of tolerance.

High-resolution 3T MR angiography of the carotid arteries: comparison of manual and semiautomated quantification of stenosis.

BACKGROUND AND PURPOSE: High-resolution contrast-enhanced MR angiography (CE-MRA) acquired at 3T exquisitely depict carotid artery (CA) stenosis. In this study, we examined the agreement of different vessel-analysis tools with manual quantitative measurement by 2 readers using CE-MRA data. MATERIALS AND METHODS: Three vessel tools determining the trajectory of the vessel of interest and, subsequently, the vessel dimensions were tested against manual measurements. Diameter and area stenoses were calculated. CE-MRA data of 32 patients with CA stenosis were evaluated. The agreement between different measurements was assessed with kappa statistics after categorizing stenosis (<25%, 25%-49%, 50%-69%, 70%-99%, and 100%). RESULTS: The mean grades of stenosis based on diameter measurements were 59% (readers) and 60%/56%/59% based on the analysis with tools A/B/C (P = 0.2-0.7). kappa values for agreement between readers and the vessel tools were 0.73/0.77/0.77 (tools A/B/C for all CAs) and 0.66/0.74/0.75 (for the symptomatic side). The mean grades of stenoses based on area measurements for tools A/B/C were 68%/63%/69% versus 58% for readers. Values from readers differed significantly from those for tools A and C (P < 0.01). kappa values for agreement between readers and the vessel tools were 0.66/0.55/0.64 (for all CAs) and 0.53/0.44/0.57 (for the symptomatic side). CONCLUSIONS: The automated approach allows accurate assessment of vessel dimensions in MRA images at least for diameter measurements according to the North American Symptomatic Carotid Endarterectomy Trial criteria.

Bone-subtraction CT angiography: evaluation of two different fully automated image-registration procedures for interscan motion compensation.

BACKGROUND AND PURPOSE: Bone-subtraction techniques have been shown to enhance CT angiography (CTA) interpretation, but motion can lead to incomplete bone removal. The aim of this study was to evaluate 2 novel registration techniques to compensate for patient motion. MATERIALS AND METHODS: Fifty-four patients underwent bone-subtraction CTA (BSCTA) for the evaluation of the neck vessels with 64-section CT. We tested 3 different registration procedures: pure rigid registration (BSCTA), slab-based registration (SB-BSCTA), and a partially rigid registration (PR-BSCTA) approach. Subtraction quality for the assessment of different vascular segments was evaluated by 2 examiners in a blinded fashion. The Cohen kappa test was applied for interobserver variability, and the Wilcoxon signed rank test, for differences between the procedures. Motion between the corresponding datasets was measured and plotted against image-quality scores. RESULTS: Algorithms with motion compensation revealed higher image-quality scores (SB-BSCTA, mean 4.31; PR-BSCTA, mean 4.43) than pure rigid registration (BSCTA, mean 3.88). PR-BSCTA was rated superior to SB-BSCTA for the evaluation of the cervical internal and external carotid arteries (P<.001), whereas there was no significant difference for the other vessels (P=.157-.655). Both algorithms were clearly superior to pure rigid registration for all vessels except the basilar and ophthalmic artery. Interobserver agreement was high (kappa=0.46-0.98). CONCLUSION: Bone-subtraction algorithms with motion compensation provided higher image-quality scores than pure rigid registration methods, especially in cases with complex motion. PR-BSCTA was rated superior to SB-BSCTA in the visualization of the internal and external carotid arteries.

Thymectomy does not abrogate long-term acceptance of MHC class I-disparate lung allografts in miniature Swine.

UNLABELLED: We have previously reported that tolerance to class I disparate lung allografts in miniature swine could be induced using an intensive 12-day course of tacrolimus and that pretransplant sensitization with immunogenic MHC class I allopeptides failed to block the induction of tolerance. We also have previously reported the importance of the presence of the thymus in the induction of tolerance to isolated heart, kidney, and combined heart-kidney transplants. In this study, we examined the impact of thymectomy on tolerance induction in lung transplantation. METHODS: Orthotopic left lung transplantation was performed using MHC class I-disparate donors. The recipients received a 12-day course of high-dose tacrolimus (n = 6). Total thymectomies were performed in three of the swine 21 days prior to transplantation. Lung grafts were monitored by chest radiography and serial open lung biopsy. RESULTS: All euthymic recipients maintained their grafts for over 1 year. None of the thymectomized recipients has experienced graft loss in the 6 to 10 months following transplantation. Although isolated lesions of obliterative bronchiolitis were occasionally seen in one thymectomized animal on biopsy, donor-specific unresponsiveness has been observed on assays of cell-mediated lymphocytotoxicity in all recipients. Moreover, co-culture assays have shown that recipient lymphocytes can strongly inhibit the normally robust response of naïve recipient-matched lymphocytes to donor antigen. This inhibition was not seen when using stimulators primed with third-party antigens against appropriate targets. CONCLUSIONS: These data suggest that thymus-independent peripheral regulatory mechanisms may be sufficient to induce and maintain long-term acceptance of the lung allografts.

The role of indirect recognition of MHC class I and II allopeptides in a fully mismatched miniature swine model of lung transplantation.

UNLABELLED: Considerable evidence suggests that indirect recognition of MHC allopeptides plays an important role in solid-organ rejection. Here, we examine whether immunization with class I or class II allopeptides accelerates rejection in a fully MHC-mismatched lung transplant model in miniature swine. METHODS: Recipients were immunized with either donor-derived class I or class II peptides. Sensitization to the peptides was confirmed by DTH testing and in vitro proliferation assays. Nonimmunized control (n = 6), class I peptide-immunized (n = 3), and class II peptide-immunized (n = 3) swine were transplanted with fully mismatched lungs using only a 12-day course of tacrolimus. RESULTS: One control animal rejected its graft on postoperative day 103, while the others maintained their grafts for over 1 year. In the class I peptide-immunized group, two recipients rejected their grafts (days 14 and 52). The third animal has not rejected the graft (day 120, experiment is ongoing). In contrast, in the class II-peptide immunized group, only one animal rejected its graft on day 52, while the others maintained their grafts over 1 year. Both anti-donor IgM and IgG antibodies were detectable in all acute rejectors, although no alloantibody was detectable in long-term acceptors. Regardless of the fate of the graft, all animals have maintained their proliferative responses to the peptides. However, only acceptors maintained donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity and mixed lymphocyte reaction assays. CONCLUSIONS: Pretransplant sensitization of lung allograft recipients to donor allopeptides accelerates graft rejection. This appears particularly true for class I-derived allopeptides, suggesting that class II molecules may be less antigenic when presented indirectly.

Montelukast improves regional air-trapping due to small airways obstruction in asthma.

Quantitative image analysis of high-resolution computed tomography (HRCT) performed at residual volume, before and after methacholine, is a sensitive method of detecting small airways involvement in asthma and response to therapy targeted to the small airways. Since an oral anti-leukotriene reaches the small airways via the circulation, the present authors hypothesised that treatment with montelukast would lead to improved small airway patency. A double-blind crossover study compared the effect of montelukast versus placebo for 4 weeks in 16 mild-to-moderate steroid-naïve asthmatics. Small airways function was evaluated by HRCT at residual volume before and after methacholine to assess regional air-trapping and airways hyperresponsiveness, as well as by physiological studies of small airways. Montelukast treatment resulted in significantly less regional air-trapping on HRCT on the pre-methacholine images when compared with placebo, as well as improvement in total quality of life scores and symptom sub-scores. However, montelukast treatment had no effect on increases in regional air-trapping on HRCT in response to methacholine. No differences were noted in global measures of small airways physiology between placebo and montelukast. In conclusion, distal airways disease improves in asthmatic subjects treated with montelukast. This improvement can be detected with high-resolution computed tomography, but not with conventional physiological studies.

On issues of confidence in determining the time constant for oxygen uptake kinetics.

BACKGROUND: TauVO(2 )at the onset of constant work rate (CWR) exercise is a variable of aerobic fitness that shortens with physical training and lengthens with cardiopulmonary disease. Determination of tauVO(2) with sufficiently high confidence has typically required multiple exercise transitions limiting its clinical application. OBJECTIVES: To design a protocol to determine tauVO(2) reliably but simply. METHODS: On each of three days, five healthy men performed two CWR tests on a cycle ergometer below the metabolic threshold (VO(2)theta) for blood lactate accumulation as determined by gas exchange measurements followed by an incremental work rate (IWR) test. TauVO(2) was determined (a) from the on-transit (on-tauVO(2)) and off-transit (off-tauVO(2)) of six CWR tests both individually and superimposed, using non-linear regression with a monoexponential model, and (b) by geometric analysis of the IWR tests (ramp-tauVO(2)). RESULTS: Group means (SD) were: VO(2)max 3.84 (0.44) litres/min, VO(2)theta 1.88 (0.23) litres/min, steady state exercise VO(2) 1.67 (0.07) litres/min, on-tauVO(2) 38.0 (5.3) seconds, off-tauVO(2) 39.0 (4.3) seconds, and ramp-tauVO(2) 60.8 (15.4) seconds. On-tauVO(2) correlated with off-tauVO(2) (r = 0.87), VO(2)max (r = -0.73), and VO(2)theta (r = 0.89). The pooled mean tauVO(2) from six superimposed tests agreed with the arithmetic grand mean of the six tests. CONCLUSIONS: The average of on-tauVO(2) and off-tauVO(2) fell within the 95% confidence interval of the pooled mean by the second test. Ramp-tauVO(2) was longer and less reproducible. These findings support the use of both on- and off-transit data for the determination of tauVO(2), an approach that reduces the number of transitions necessary for accurate determination of tauVO(2), potentially enhancing its clinical application.

Clinical assessment of a radiolucent cushion for mammography.

PURPOSE: To determine whether use of a radiolucent cushion could significantly decrease pain during screening mammography without compromising image quality or other technical factors. MATERIAL AND METHODS: 838 patients presenting for routine screening mammography were evaluated. The radiolucent cushions were placed on the compression surfaces of the mammographic equipment and were used while imaging the right breast. No pads were used while imaging the left breast. Patient age, hormonal status, compression force, and radiation dose values were collected on all patients. Each subject completed a visual analog pain scale (VAS) rating the degree of pain experienced with and without the cushions. All mammographic images obtained (CC and MLO views) were compared, side by side (cushioned versus non-cushioned) by the readers. RESULTS: Use of radiolucent cushions reduced pain by 10% or more in 66% (555/838) of women. Patients in this "benefited group" experienced an average pain reduction of 53%. No compromise of image quality was observed. Compression force and radiation dose values were highly correlated between the cushioned and non-cushioned sides. CONCLUSION: Two-thirds of women experienced a significant reduction of pain when the radiolucent cushions were used during mammography. Pain reduction was accomplished without any clinically significant change in compression force, radiation dose values, or image quality.

Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier.

BACKGROUND: Monocyte/macrophages are known to infiltrate the brain of patients with HIV-1 encephalitis (HIVE). In Alzheimer's disease brain, the origin of activated microglia has not been determined. MATERIALS AND METHODS: We employed the antigen retrieval technique, immunocytochemistry, immunofluorescense, and confocal microscopy to identify macrophages and microglia in relation to amyloid-beta plaques and the blood-brain barrier in autopsy brain tissues from patients with Alzheimer's disease (AD) and HIVE. RESULTS: In both conditions, cyclooxygenase-2 positive macrophages and, to a lesser degree, T and B cells infiltrate brain perivascular spaces and neuropil. The macrophages are distinguishable from ramified microglia, and decorate the vessels at the sites of apparent of endothelial tight junction protein ZO-1 disruption. The macrophages also infiltrate amyloid-beta plaques, display intracellular amyloid-beta and are surrounded by amyloid-beta-free lacunae. Furthermore, the macrophages partially encircle the walls of amyloid-beta-containing vessels in amyloid angiopathy, and exhibit intracellular amyloid-beta but not paracellular lacunae. Significantly larger zones of fibrinogen leakage surround the microvessels in HIVE brain tissues compared with AD tissues (P = 0.034), and AD tissues have significantly greater leakage than control tissues (P = 0.0339). The AD group differs from a normal control age-matched group with respect to both the area occupied by CD68 (P = 0.03) and cyclooxygenase-2 immunoreactive cells (P = 0.004). CONCLUSION: In both HIVE and AD, blood-borne activated monocyte/macrophages and lymphocytes appear to migrate through a disrupted blood-brain barrier. The lacunae around macrophages in amyloid-beta plaques but not in vessel walls are consistent with the ability of macrophages to phagocytize and clear amyloid-beta deposits in vitro.

Impact study of tobacco possession law enforcement in Florida.

This study of tobacco possession law enforcement was conducted in four selected counties in Florida, the first state to report statistically significant annual declines in youth tobacco use during the 1990s. The primary objective of this study was to assess the impact of possession enforcement on youth attitudes, perceptions, and behaviors by comparing results of a survey administered in high-enforcement counties with results from low-enforcement counties and by examining the survey results for relationships of tobacco use to perceptions and awareness of laws and enforcement activity. The survey was administered to a sample of 2,088 randomly selected youth, in conjunction with a qualitative study of law enforcement officials reported elsewhere. Findings indicate that possession enforcement, as a component of comprehensive tobacco control, appears to help reduce youth tobacco use and may be a critical component of the most successful youth tobacco prevention program, documented in the previous decade.

Essential role of HIV type 1-infected and cyclooxygenase 2-activated macrophages and T cells in HIV type 1 myocarditis.

HIV-1 cardiomyopathy has become a major cause of death in AIDS patients, but its pathogenesis is unclear. We used an antigen retrieval technique and immunostaining to investigate the hearts of 15 AIDS patients, of whom 3 had dilated cardiomyopathy. Immunocytochemistry shows infiltration of the left ventricular myocardium with mononuclear cells, ranging from minimal to diagnostic of myocarditis. The infiltrates include macrophages and CD3(+) and CD8(+) T cells. The tight junction protein ZO-1 is disrupted at the site of monocyte-macrophage vascular penetration and the coronary vessels show fibrinogen leakage in the hearts of AIDS patients, but not in the normal heart. A subset of infiltrating macrophages is doubly positive for cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase. HIV-1 peptides gp120 and Nef are expressed in macrophages and T cells, but not in cardiomyocytes. COX-2 is expressed by both gp120-positive and gp120-negative macrophages. The hearts of AIDS patients separate into those showing minimal infiltrates with low COX-2 expression and those with dense infiltrates and high COX-2; all failing hearts are in the latter group. These data suggest that COX-2-activated and HIV-1-infected monocyte-macrophages and T cells play a crucial role in the progression of HIV-1 myocarditis to HIV-1 cardiomyopathy.