Pulmonary vascular morphology as an imaging biomarker in chronic thromboembolic pulmonary hypertension.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three-dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small-vessel volume: 2.7 [interquartile range (IQR): 2.5-3.0] vs. 3.2 [3.0-3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30-0.41] vs. 0.23 [0.21-0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92% [IQR: 4.85%-5.21%] vs. 4.63% [4.39%-4.92%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes.

Relation of vitamin D status to congestive heart failure and cardiovascular events in dogs.

BACKGROUND: Vitamin D plays a pivotal role in cardiac function, and there is increasing evidence that vitamin D deficiency is associated with the development of congestive heart failure (CHF) in people. HYPOTHESIS: Serum vitamin D concentration is lower in dogs with CHF compared with unaffected controls and serum vitamin D concentration is associated with clinical outcome in dogs with CHF. ANIMALS: Eighty-two client-owned dogs. METHODS: In this cross-sectional study, we examined the association between circulating 25-hydroxyvitamin D [25(OH)D], a measure of vitamin D status, and CHF in dogs. In the prospective cohort study, we examined whether 25(OH)D serum concentration was associated with clinical outcome in dogs with CHF. RESULTS: Mean 25(OH)D concentration (100 ± 44 nmol/L) in 31 dogs with CHF was significantly lower than that of 51 unaffected dogs (123 ± 42 nmol/L; P = .023). The mean calculated vitamin D intake per kg of metabolic body weight in dogs with CHF was no different from that of unaffected dogs (1.37 ± 0.90 µg/kg metabolic body weight versus 0.98 ± 0.59 µg/kg body weight, respectively, P = .097). There was a significant association of serum 25(OH)D concentration on time to clinical manifestation of CHF or sudden death (P = .02). CONCLUSION AND CLINICAL RELEVANCE: These findings suggest that low concentrations of 25(OH)D may be a risk factor for CHF in dogs. Low serum 25(OH)D concentration was associated with poor outcome in dogs with CHF. Strategies to improve vitamin D status in some dogs with CHF may prove beneficial without causing toxicity.

Temperature dependence of the nitrogen-vacancy magnetic resonance in diamond.

The temperature dependence of the magnetic-resonance spectra of nitrogen-vacancy (NV-) ensembles in the range of 280-330 K was studied. Four samples prepared under different conditions were analyzed with NV- concentrations ranging from 10 ppb to 15 ppm. For all samples, the axial zero-field splitting (ZFS) parameter D was found to vary significantly with temperature, T, as dD/dT=-74.2(7) kHz/K. The transverse ZFS parameter E was nonzero (between 4 and 11 MHz) in all samples, and exhibited a temperature dependence of dE/(EdT)=-1.4(3)x10{-4} K-1. The results might be accounted for by considering local thermal expansion. The temperature dependence of the ZFS parameters presents a significant challenge for diamond magnetometers and may ultimately limit their bandwidth and sensitivity.

Retroreflecting polarization spectroscopy enabling miniaturization.

We describe and characterize alternative configurations for Doppler-free polarization spectroscopy. The suggested apparatus enables complete pump/probe beam overlap and allows substantial miniaturization. Its utility and performance for narrow linewidth, high-stability frequency locking is discussed for the /5S(1/2)F=2>-->/5P(3/2)F(')>D(2) transition in (87)Rb.

Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study.

PURPOSE: To evaluate the response rate, toxicity profile, and pharmacokinetics of ecteinascidin-743 (ET-743) as first-line therapy in patients with unresectable advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: Thirty-six patients with STS were enrolled onto the study between September 1999 and August 2000. Patients were treated with 1.5 mg/m2 of ET-743 given as a 24-hour continuous intravenous (IV) infusion every 21 days. Pharmacokinetic sampling was performed in 23 patients. RESULTS: One complete and five partial responses were achieved in 35 assessable patients for an overall response rate of 17.1% (95% CI, 6.6% to 33.6%). In addition, one patient had a minor response, leading to an overall clinical benefit of 20%. Neutropenia and transaminitis were the main grade 3 to 4 toxicities, which occurred in 33% and 36% of the patients. The estimated 1-year progression-free and overall survival rates were 21% (95% CI, 11% to 41%) and 72% (95% CI, 59% to 88%), respectively. Total body clearance (L/h) was not significantly correlated with body-surface area (r = -0.28; P = .21). Mild hepatic impairment or the extent of prior cytotoxic therapy does not seem to contribute significantly to the high interpatient variability (49%) in the clearance of this drug. Severity of treatment-related toxicity was not correlated with pharmacokinetic variables. CONCLUSION: ET-743 demonstrates clinical activity as first-line therapy against STS with acceptable toxicity. Additional studies to establish empirical dosing guidelines may be necessary to improve the safety of the drug in patients with varying degrees of hepatic dysfunction and definitively establish the role of ET-743 for patients with these malignancies.

Aortic root infection in a prosthetic valve demonstrated by gallium-67 citrate SPECT.

A 70-year-old man presented with 6 weeks of worsening low back pain, fever, sweating, and weight loss with known severe lumbosacral osteoarthritis. His history included CABG in 1992, porcine aortic valve replacement, and permanent pacemaker implantation in 2002. CT of the chest, abdomen, and pelvis did not demonstrate a cause for the symptoms. Blood cultures grew penicillin-sensitive enterococcus and he was referred for evaluation of possible osteodiskitis or epidural abscess. Gallium planar imaging demonstrated increased activity in the lumbar spine, suspicious for the presence of infection, and activity was noted in the mid mediastinum as well. SPECT clearly showed increased Ga-67 activity in the region of the aortic root, suspicious for infection. A perivalvular aortic root abscess was subsequently demonstrated by transesophageal echo. This case illustrates the value of Ga-67 chest SPECT in patients with prosthetic valves for detection of endocarditis.

Public-private health partnerships: a strategy for WHO.

Following early success with a number of high-profile partnerships, WHO is increasingly working with the private for-profit sector. In so doing, the organization finds itself in the maelstrom of a vibrant debate on the roles of public, civic, and commercial entities in society and on the appropriate modes of interaction among them. This paper examines WHO's involvement with the commercial sector, particularly in partnerships. WHO's approach to this sector is outlined and the criticisms levelled at public-private partnerships are reviewed. An indication is given of the steps recently taken by WHO to confront the concerns that have been expressed. The paper argues that partnership between WHO and the commercial sector is inevitable and that it presents considerable opportunities, but also significant risks, for the organization and for public health. A strategy is proposed for directing the debate on issues critical to WHO and its role in the promotion and protection of public health.

The nonimpact of thyroid stunning: remnant ablation rates in 131I-scanned and nonscanned individuals.

Thyroid stunning has been reported as the temporary impairment of thyroid tissue after a 111-MBq or greater diagnostic 131I dose that decreases the final absorbed dose in ablative therapy. Concerns regarding the reality of stunning have arisen in part due to a flawed study design in prior reports. To assess whether a stunning effect has any impact on therapeutic outcomes, we compared initial treatment ablation rates in patients who received 111- to 185-MBq 131I diagnostic scans (n = 37) before ablative doses of 3700-7400 MBq with ablation rates in patients who did not receive any 131I before the initial treatment dose (n = 63). Ablation rates were 64.9% for scanned patients and 66.7% for nonscanned patients, a nonsignificant difference. Nonscanned patients with metastatic lesions (n = 23) were ablated at a higher rate (78.3%) than scanned patients (n = 9) (66.7%), but the difference was not significant (P = 0.50). It is possible that the reported stunning phenomenon, specifically its impact in temporarily impairing tissue, has been overemphasized.

Reevaluation of the impact of a stringent low-iodine diet on ablation rates in radioiodine treatment of thyroid carcinoma.

Prior analyses of the impact of stringent, preablative low-iodine diets (LIDs) on ablation in patients with differentiated thyroid cancer postthyroidectomy are dated. We retrospectively reviewed first-time, short-term ablation rates for 44 LID patients and 50 patients following a regular diet (RD) who were verbally instructed to avoid salt, seafood, and multivitamins containing iodine. Patients who had undergone ablation were given between 100 and 200 mCi of 131I, depending on the presence of metastases. We found a 68.2% ablation rate for LID patients, compared to a 62.0% rate for RD patients, a nonsignificant difference (p = 0.53). We observed a dose-response relationship for both patient groups, with higher ablation rates corresponding to higher doses of radioiodine administered. We also measured iodine levels in spot urine samples from 7 matched LID patients and 7 matched RD adherents (healthy volunteers) prediet and postdiet as well as 39 healthy volunteers. LID patients had a lower mean urinary iodine level postdiet (173.9 microg/L; range, 45-1,217 microg/L; standard deviation [SD] = 127.7) than the RD patients (mean, 381.4 microg/L; range, 140-630 microg/L; SD = 196.3) or the 39 normal controls (444.0 microg/L; range, 50-1,690 microg/L; SD = 413.4). Whereas the LID lowered urinary iodine levels by 69.4% from prediet values, the RD reduced urinary iodine by 23.6%. Although differences in the reduction of urinary iodine levels between the LID and the RD were substantial, both groups experienced equivalent outcomes. The level of iodine in the American diet has progressively decreased, and may be much lower now than when prior LID studies were conducted. We suggest that prescribing a refined, less stringent diet that avoids high-iodine-containing foods would offer equivalent outcomes with increased patient convenience.

Pulmonary function test abnormalities in pulmonary vascular disease and chronic heart failure.

Diagnostic criteria based on pulmonary function testing for pulmonary vascular disease and CHF are imprecise. Although these tests constitute a necessary part of the work-up of a patient with dyspnea, additional studies are required to obtain a final diagnosis in the setting of cardiopulmonary vascular disease. In contrast, specific pulmonary function tests may offer an objective means of assessing severity of dysfunction resulting from pulmonary hypertension or CHE Serial measurements of pulmonary function offer insight into general and specific patterns of cardiopulmonary vascular disease and are useful in evaluating response to treatment.

Accuracy considerations when using early (four- or six-hour) radioactive iodine uptake to predict twenty-four-hour values for radioactive iodine dosage in the treatment of Graves' disease.

Although literature has offered methods to predict 24-hour radioactive iodine uptake values from early (4- to 6-hour) measurements, the resultant dosage errors have not been examined. Potential errors include underdosage, overdosage, and a failure to recognize rapid turnover patients (early-to-late uptake ratios > or = 1) who are at high risk for treatment failure and full-body radiation exposure. We developed and tested a novel method for minimizing error involved in using a single early uptake measurement to derive late uptake. From a retrospective analysis of 203 Graves' disease patients, receiver operating characteristic (ROC) curve analysis enabled us to identify patients likely to experience rapid turnover and therefore should receive 24-hour studies. Twenty-four-hour uptake measurements are necessary with 77% or more 4-hour uptake values and 80% or more 6-hour values. After eliminating these patients, we developed linear regression equations to predict the 24-hour uptake from 4-hour (n = 61) and 6-hour (n = 22) rule groups, testing their efficacy on separate 4-hour (n = 61) and 6-hour (n = 21) patient groups. We also used our test population to measure error in four early-to-late uptake conversion formulas presented in the literature. Error involved in these predictions ranged from a 10.6% overestimate for 4-hour calculations to a 5.9% underestimate for 6-hour calculations. When applied to two dosage formulas incorporating gland size, absorbed dose, and 24-hour uptake, average dosage error was 7%. In comparison to the other sources of error radioactive iodine (131I) dosimetry, potential error in predicting 24-hour uptake from 4- or 6-hour uptake values is low.

IL-13 stimulates vascular endothelial cell growth factor and protects against hyperoxic acute lung injury.

Hyperoxia is an important cause of acute lung injury. To determine whether IL-13 is protective in hyperoxia, we compared the survival in 100% O(2) of transgenic mice that overexpress IL-13 in the lung and of nontransgenic littermate controls. IL-13 enhanced survival in 100% O(2). One hundred percent of nontransgenic mice died in 4-5 days, whereas 100% of IL-13-overexpressing mice lived for more than 7 days, and many lived 10-14 days. IL-13 also stimulated VEGF accumulation in mice breathing room air, and it interacted with 100% (2) to increase VEGF accumulation further. The 164-amino acid isoform was the major VEGF moiety in bronchoalveolar lavage from transgenic mice in room air, whereas the 120- and 188-amino acid isoforms accumulated in these mice during hyperoxia. In addition, antibody neutralization of VEGF decreased the survival of IL-13-overexpressing mice in 100% (2). These studies demonstrate that IL-13 has protective effects in hyperoxic acute lung injury. They also demonstrate that IL-13, alone and in combination with 100% (2), stimulates pulmonary VEGF accumulation, that this stimulation is isoform-specific, and that the protective effects of IL-13 are mediated, in part, by VEGF.

Functional brain imaging in the assessment of multiple chemical sensitivities.

The author provides a brief overview of single photon emission computed tomography in the assessment of multiple chemical sensitivities.

What do adolescent females know about breast cancer and prevention?

Background: Many lifelong habits begin during adolescence. These habits can have profound, long-term ramifications on health. An important health habit is self-breast examination (SBE). The purpose of this study is to assess adolescent females' knowledge of breast cancer and breast cancer prevention. A survey was developed with questions that focused on female adolescents' knowledge of these topics. This information will assist health professionals in educating teens and forming public policy.Methods: Anonymous surveys consisting of ten questions were distributed to 280 females aged 13-17. These questions pertained to breast cancer with an emphasis on SBE, mammography, and risk factors. Questions were analyzed by chi square calculations. An additional section of the survey contained demographic characteristics of the respondents. Parental consent was obtained prior to completion of the surveys in accordance with the Institutional Review Board at St. Luke's Hospital. Surveys were administered during health class in a local high school.Results: One hundred and fifteen surveys were returned. Ages of participants were 13 to 17. The ethnic background of all participants were similar in that the majority were Caucasian. The overall percentage of correct answers was 65%. The majority of students knew what a mammogram is (92%) and how often screening should occur (65%), however, only 25% knew at what age screening should begin. It was encouraging that 80% of the students knew how often to perform SBE although only about half (53%) knew the time of the month this should be done. It was also encouraging that 83% knew that breast cancer is the second leading cause of cancer death, but the knowledge regarding risk factors that could possibly affect them was poor (36%). A statistically significant findings was that in the twenty percent of the students who had been taught SBE, 10 (43.5%) actually perform them. This is in relation to 2.2% of students who perform exams without any prior instruction. There was no statistically significant difference in the final score between students who had been taught how to perform exams and students who had not.Conclusions: Developing sound health habits as an adolescent should transcend to good health maintenance practices as an adult. Our study showed that adolescent females significantly lack knowledge relating to breast cancer. Adolescent females need to be better educated on the basic facts, including risk factors, screening procedures and SBE. With the incidence of breast cancer so high, knowledge of breast cancer and its prevention may result in earlier diagnosis and subsequently better long term outcomes.

Interleukin-6-induced protection in hyperoxic acute lung injury.

Hyperoxic lung injury is commonly encountered in patients who require treatment with high concentrations of inspired oxygen. To determine whether interleukin (IL)-6 is protective in oxygen toxicity, we compared the effects of 100% O(2) in transgenic mice that overexpress IL-6 in the lung and transgene (-) controls. IL-6 markedly enhanced survival, with 100% of transgene (-) animals dying within 72 to 96 h, 100% of transgene (+) animals living for more than 8 d and more than 90% of transgene (+) animals living longer than 12 d. This protection was associated with markedly diminished alveolar-capillary protein leak, endothelial and epithelial membrane injury, and lung lipid peroxidation. Hyperoxia also caused cell death with DNA fragmentation in the lungs of transgene (-) animals and IL-6 markedly diminished this cytopathic response. The protective effects of IL-6 were not associated with significant alterations in the activities of copper/ zinc superoxide dismutase (SOD) or manganese SOD. They were, however, associated with the enhanced accumulation of the cell-death inhibitor Bcl-2, but not the cell-death stimulator BAX, and with the heightened accumulation of the cell-death regulator tissue inhibitor of metalloproteinase-1 (TIMP-1). These studies demonstrate that IL-6 markedly diminishes hyperoxic lung injury and that this protection is associated with a marked diminution in hyperoxia-induced cell death and DNA fragmentation. They also demonstrate that this protection is not associated with significant alterations in SOD activity, but is associated with the induction of Bcl-2 and TIMP-1.