Ecological risk assessment of endocrine disruptors.

The European Centre for Ecotoxicology and Toxicology of Chemicals proposes a tiered approach for the ecological risk assessment of endocrine disruptors, integrating exposure and hazard (effects) characterization. Exposure assessment for endocrine disruptors should direct specific tests for wildlife species, placing hazard data into a risk assessment context. Supplementing the suite of mammalian screens now under Organization for Economic Cooperation and Development (OECD) validation, high priority should be given to developing a fish screening assay for detecting endocrine activity in oviparous species. Taking into account both exposure characterization and alerts from endocrine screening, higher tier tests are also a priority for defining adverse effects. We propose that in vivo mammalian and fish assays provide a comprehensive screening battery for diverse hormonal functions (including androgen, estrogen, and thyroid hormone), whereas Amphibia should be considered at higher tiers if there are exposure concerns. Higher tier endocrine-disruptor testing should include fish development and fish reproduction tests, whereas a full life-cycle test could be subsequently used to refine aquatic risk assessments when necessary. For avian risk assessment, the new OECD Japanese quail reproduction test guideline provides a valuable basis for developing a test to detecting endocrine-mediated reproductive effects; this species could be used, where necessary, for an avian life-cycle test. For aquatic and terrestrial invertebrates, data from existing developmental and reproductive tests remain of high value for ecological risk assessment. High priority should be given to research into comparative endocrine physiology of invertebrates to support data extrapolation to this diverse fauna.

Assessment of coronary arterial restenosis with phase-contrast magnetic resonance imaging measurements of coronary flow reserve.

BACKGROUND: After successful percutaneous coronary arterial revascularization, 25% to 60% of subjects have restenosis, a recurrent coronary arterial narrowing at the site of the intervention. At present, restenosis is usually detected invasively with contrast coronary angiography. This study was performed to determine if phase-contrast MRI (PC-MRI) could be used to detect restenosis noninvasively in patients with recurrent chest pain after percutaneous revascularization. METHODS AND RESULTS: Seventeen patients (15 men, 2 women, age 36 to 77 years) with recurrent chest pain >3 months after successful percutaneous intervention underwent PC-MRI measurements of coronary artery flow reserve followed by assessments of stenosis severity with computer-assisted quantitative coronary angiography. The intervention was performed in the left anterior descending coronary artery in 15 patients, one of its diagonal branches in 2 patients, and the right coronary artery in 1 patient. A PC-MRI coronary flow reserve value /=70% and >/=50%, respectively. CONCLUSIONS: Assessments of coronary flow reserve with PC-MRI can be used to identify flow-limiting stenoses (luminal diameter narrowings >70%) in patients with recurrent chest pain in the months after a successful percutaneous intervention.

Visualization and functional assessment of proximal and middle left anterior descending coronary stenoses in humans with magnetic resonance imaging.

BACKGROUND: Coronary artery bypass grafting improves survival in patients with >70% luminal diameter narrowing of the 3 major epicardial coronary arteries, particularly if there is involvement of the proximal portion of the left anterior descending (LAD) coronary artery. Measurement of coronary flow reserve can be used to identify functionally important luminal narrowing of the LAD artery. Although magnetic resonance imaging (MRI) has been used to visualize coronary arteries and to measure flow reserve noninvasively, the utility of MRI for detecting significant LAD stenoses is unknown. METHODS AND RESULTS: Thirty subjects (23 men, 7 women, age 36 to 77 years) underwent MRI visualization of the left main and LAD coronary arteries as well as measurement of flow in the proximal, middle, or distal LAD both at rest and after intravenous adenosine (140 microgram/kg per minute). Immediately thereafter, contrast coronary angiography and when feasible, intracoronary Doppler assessments of coronary flow reserve, were performed. There was a statistically significant correlation between MRI assessments of coronary flow reserve and (a) assessments of coronary arterial stenosis severity by quantitative coronary angiography and (b) invasive measurements of coronary flow reserve (P<0.0001 for both). In comparison to computer-assisted quantitative coronary angiography, the sensitivity and specificity of MRI for identifying a stenosis >70% in the distal left main or proximal/middle LAD arteries was 100% and 83%, respectively. CONCLUSIONS: Noninvasive MRI measures of coronary flow reserve correlated well with similar measures obtained with the use of intracoronary Doppler flow wires and predicted significant coronary stenoses (>70%) with a high degree of sensitivity and specificity. MRI-based measurement of coronary flow reserve may prove useful for identification of patients likely to obtain a survival benefit from coronary artery bypass grafting.

Environmental risk assessment for the widely used iodinated X-ray contrast agent iopromide (Ultravist).

Iodinated X-ray contrast media are diagnostic pharmaceuticals that are applied to enhance the contrast between organs or vessels examined and surrounding tissues during radiography. These substances are applied in doses up to ca. 200 g per person (corresponding to approx 100 g iodine) and are rapidly excreted. In the sewage system they contribute to the burden of adsorbable organic halogens (AOX). To assess the potential environmental impact of this release, studies on environmental fate and effects were conducted for a risk assessment of the frequently used X-ray contrast medium iopromide (brand name: Ultravist). A screening test for biological degradation (OECD Screening Test 301 E) led to iopromide being classified as not readily biodegradable. Therefore, the predicted environmental concentration (PEC) in surface water was calculated in a first step. The resulting concentration of 2 microgram/liter was then compared in a second step with the predicted no-effect concentration as derived from a battery of ecotoxicity tests. In short-term toxicity tests with bacteria (Vibrio fisheri, Pseudomonas putida), algae (Scenedesmus subspicatus), crustaceans (Daphnia magna), and fish (Danio rerio, Leuciscus idus) no toxic effects were detected at the highest tested concentration of 10 g/liter. In a chronic toxicity test with D. magna no effect was observed at the highest tested concentration of 1 g/liter. Using an assessment factor of 100 the ratio between the predicted environmental concentration (PEC) and the predicted no-effect concentration (PNEC) was calculated to be

An assessment of contextual mediation in trance states of shamanic journeys.

30 experiences of shamanic journeys derived from Harner (1990) were analyzed based on a recent coding scheme for contextual variables proposed by Lange, Houran, Harte, and Havens. Consistent with previous research, the experiential content of the trances was quite consistent with the content of the available contextual variables, and embedded cues in particular (r = .68, p < .001). As predicted, trance states of shamanic journeys are sufficiently structured to suppress contextual effects on the modality of experience. The findings suggest that the contents of shamanic trance are not solely influenced by psychopathology, biochemical effects, or cultural influences.

Percutaneous tracheostomy: a cost-effective alternative to standard open tracheostomy.

Percutaneous tracheostomy was initiated as an alternative to open tracheostomy at our institution in December 1993. To assess safety, operative time, and cost, a comparative analysis of percutaneous and open tracheostomies was performed. A retrospective evaluation of all patients who underwent percutaneous tracheostomy (P) from December 1993 to March 1996 was completed. Patients were evaluated for indications for tracheostomy, length of operation, morbidity, and cost. The results were compared with patients who underwent open tracheostomy (O) during the 12 months prior to introduction of the percutaneous technique. Tracheostomy was performed percutaneously in 74 patients and by a standard open technique in 109 patients. Indications for tracheostomy included: chronic ventilator dependence (P, 49 vs O, 58); airway protection (P, 19 vs O, 42); laryngeal dysfunction (P, 2 vs O, 7); and facial trauma (P 6 vs O, 2). The length of operation was 21 +/- 6 minutes and 46 +/- 21 minutes for percutaneous and open tracheostomy, respectively (P < 0.05). Perioperative morbidity occurred in 2 patients (3%) following percutaneous tracheostomy compared to 10 patients (9%) following open tracheostomy (P > 0.05). The mean operating room costs per patient were $1093 and $1370 for percutaneous and open tracheostomy, respectively. Percutaneous tracheostomy is a safe procedure that can be performed in less time and at a lower cost than standard open tracheostomy.

A critical reappraisal of the oximetric assessment of intracardiac left-to-right shunting in adults.

Although the oximetric analysis of blood from the right heart chambers is the most commonly used method for assessing the presence of intracardiac left-to-right shunting, the data the analysis is based on are limited. In addition, uncertainty exists concerning the best way of estimating the mixed venous oxygen content in subjects with intraatrial left-to-right shunting. In 102 adults without left-to-right shunting, blood was obtained from the venae cavae and right heart chambers to measure oxygen content. The limits of normality of oxygen content differences were 0.5 ml/dl from venae cavae to right atrium, 0.6 ml/dl from right atrium to right ventricle, and 0.9 ml/dl from right ventricle to pulmonary artery. The pulmonary arterial oxygen content was best estimated by combining the superior and inferior vena caval oxygen contents according to the formula (2[SVC] + 3[IVC]) divided by 5, where SVC is the superior vena cava and IVC is the inferior venae cava. These data provide new oximetric criteria for establishing the presence of intracardiac left-to-right shunting in adults.

Economic impact of replacing CT with MR imaging for refractory epilepsy.

PURPOSE: To evaluate the economic costs of using computed tomography (CT) vs. magnetic resonance (MR) imaging in the preoperative evaluation of refractory epilepsy patients. METHODS: Preoperative CT and MR imaging findings from 117 patients who underwent surgery for medically refractory epilepsy during a 3.5-year period were reviewed. Cost savings were based on the paradigm that intracranial electroencephalogram monitoring (costing about $50,000) would have been necessary for preoperative localization of the epileptogenic zone in those patients without positive imaging findings. Savings attributed to replacing CT with MR were based on patients with positive MR and normal CT. A similar paradigm was used to calculate savings for replacing MR with CT. National savings were based solely on patients with neoplasms or vascular lesions because paradigms for other lesions vary considerable depending on institutional philosophy. RESULTS: Replacing CT with MR imaging would have eliminated preoperative intracranial electrode procedures in 29 of 117 patients, with potential savings of $1,450,000 at our institution. In the 37 patients with neoplastic or vascular substrates, MR would have eliminated 10 invasive electrode procedures with estimated savings of $0.5 million institutionally and $3 to $4 million per year nationally. There were no cases to support replacing MR with CT. CONCLUSION: Replacing CT with MR decreases health costs associated with preoperative evaluation of intractable epilepsy requiring surgical amelioration.

Assessment of coronary arterial flow and flow reserve in humans with magnetic resonance imaging.

BACKGROUND: The noninvasive measurement of absolute epicardial coronary arterial flow and flow reserve would be useful in the evaluation of patients with coronary circulatory disorders. Phase-contrast magnetic resonance imaging (PC-MRI) has been used to measure coronary arterial flow in animals, but its accuracy in humans is unknown. METHODS AND RESULTS: Twelve subjects (7 men, 5 women: age 44 to 67 years) underwent PC-MRI measurements of flow in the left anterior descending coronary artery or one of its diagonal branches at rest and after administration of adenosine (140 microgram . kg(-1) . min (-1) IV). Immediately thereafter, intracoronary Doppler velocity (IDV) and flow measurements were made during cardiac catheterization at rest and after intravenous administration of adenosine. For the 12 patients, the correlation between MRI and invasive measurements of coronary arterial flow and coronary arterial flow reserve was excellent: coronary flow (MRI) (mL/min)= 0.85 x coronary flow (IDV) (mL/min)+17 (mL/min), r=.89, and coronary flow reserve (MRI) =0.79 x coronary velocity reserve (IDV) + 0.34, r=.89. For the range of coronary arterial flows (18 to 161 mL/min) measured by MRI, the limit of agreement between MRI and catheterization measurements of flow was -13+/-30 mL/min; for the range of coronary reserves (0.7 to 3.7) measured by MRI, the limit of agreement between the two techniques was 0.1+/-0.4. CONCLUSIONS: Cine velocity-encoded PC-MRI can noninvasively measure absolute coronary arterial flow in the left anterior descending artery in humans. PC-MRI can detect pharmacologically induced changes in coronary arterial flow and can reliably distinguish between those subjects with normal and abnormal coronary artery flow reserve.

Magnetic resonance imaging assessment of the severity of mitral regurgitation. Comparison with invasive techniques.

BACKGROUND: In the patient with mitral regurgitation who is being considered for valvular surgery, cardiac catheterization is usually performed to quantify the severity of regurgitation and to determine its influence on left ventricular volumes and systolic function. Magnetic resonance imaging (MRI) potentially provides a rapid, noninvasive method of acquiring these data. Thus, this study was done to determine whether MRI can reliably measure the magnitude of mitral regurgitation and evaluate the effect of regurgitation on left ventricular volumes and systolic function. METHODS AND RESULTS: Twenty-three subjects (14 women and 9 men 15 to 72 years of age) with (n = 17) or without (n = 6) mitral regurgitation underwent MRI scanning followed immediately by cardiac catheterization. The presence (or absence) of valvular regurgitation was determined, and left ventricular volumes and regurgitant fraction were quantified during each procedure. There was excellent correlation between invasive and MRI assessments of left ventricular end-diastolic (r = .95) and end-systolic (r = .95) volumes and regurgitant fraction (r = .96). All MRI examinations were completed in < 28 minutes. CONCLUSIONS: In the patient with mitral regurgitation, MRI compares favorably with cardiac catheterization for assessment of the magnitude of regurgitation and its influence on left ventricular volumes and systolic function.

Assessment of left-to-right intracardiac shunting by velocity-encoded, phase-difference magnetic resonance imaging. A comparison with oximetric and indicator dilution techniques.

BACKGROUND: Velocity-encoded, phase-difference magnetic resonance imaging (MRI) has been shown to provide an accurate assessment of shunt magnitude in patients with large atrial septal defects, but its ability to determine shunt magnitude in patients with intracardiac left-to-right shunts of various locations and sizes has not been evaluated in a prospective and blinded manner. The objective of the present study was to determine whether velocity-encoded, phase-difference MRI can assess the magnitude of intracardiac left-to-right shunting in humans. METHODS AND RESULTS: Twenty-one subjects (15 women and 6 men; age range, 15 to 72 years) underwent velocity-encoded, phase-difference MRI measurements of flow in the proximal aorta and pulmonary artery, followed immediately by cardiac catheterization. The presence of left-to-right intracardiac shunting was assessed with hydrogen inhalation, after which shunt magnitude was measured by the oximetric and indocyanine green techniques. Of the 21 patients, 12 had left-to-right intracardiac shunting detected by hydrogen inhalation. There was a good correlation (r = .94) between the invasive and MRI assessments of shunt magnitude. In comparison to oximetry and indocyanine green, MRI correctly identified the 12 patients with a ratio of pulmonary to systemic flow (Qp/Qs) of < 1.5 (9 without intracardiac shunting and 3 with small shunts) and the 9 patients with a Qp/Qs of > or = 1.5 (6 with atrial septal defect, 1 with ventricular septal defect, 1 with patent ductus arteriosus, and 1 with both atrial septal defect and patent ductus arteriosus). CONCLUSIONS: Compared with measurements obtained during cardiac catheterization, velocity-encoded, phase-difference MRI measurements of flow in the proximal great vessels can reliably assess the magnitude of intracardiac left-to-right shunting.

Clinical stage I endometrial carcinoma: pitfalls in preoperative assessment with MR imaging. Work in progress.

PURPOSE: To identify potential pitfalls in using magnetic resonance (MR) imaging to determine the depth of myometrial invasion in patients with clinical stage I endometrial carcinoma. MATERIALS AND METHODS: Forty women with clinical stage I endometrial carcinoma underwent preoperative pelvic MR imaging. Uterine length, tumor signal intensity, appearance of the junctional zone, presence of large polypoid tumors, leiomyomata, and congenital uterine anomalies were analyzed. Univariate logistic-regression analysis was performed to identify associations between incorrect MR staging and these variables. RESULTS: MR staging of IA, IB, and IC disease was 55% accurate (22 of 40 cases); MR differentiation of deep myometrial invasion (stage IC) from superficial disease (stages IA and IB) was 78% accurate (31 of 40 cases). Older age (P = .025), presence of polypoid tumors (P = .025), and difficulty in pathologic staging (P < .005) were significantly associated with incorrect MR assessment. CONCLUSION: When present, large polypoid tumors, leiomyomata, congenital anomalies, small uteri, and indistinct zonal anatomy may make it difficult to assess myometrial invasion at MR imaging.

The violence management team. An approach to aggressive behaviour in a general hospital.

OBJECTIVES: To describe the establishment of a violence management team (VMT) to manage patients who exhibit violent behaviour in a general hospital (Flinders Medical Centre), and to review data collected in the first 44 months of operation. METHODS: The VMT consisted of a doctor, a senior nurse and four orderlies. Calls to the team were recorded and audited. Data were collected from patient case notes and supplemented, where necessary, with information from medical and nursing staff. RESULTS: There were 282 calls for the VMT during the study period, most often to patients with organic mental disorders (45%), substance abuse disorders (18%) and personality disorders (15%). In 30% of calls, verbal placation alone was sufficient to manage the patient; however, 62% of patients needed physical restraint (i.e., were physically held by team members) and 53% were administered a sedative medication. CONCLUSIONS: Violent behaviour in patients in a general hospital is an important problem, often caused by organic mental disorders. This, and the need to restrain aggressive patients so that they can receive essential medical care, suggest that such behaviour should be treated as a clinical problem rather than one for security guards or the police. The VMT provides a mechanism for dealing with aggressive patients which ensures good patient management, as well as protecting the health and safety of staff. It is also a monitor for quality assurance purposes, and provides data to determine the causes of patient violence and to implement prevention programs.

Female pelvis: impact of MR imaging on treatment decisions and net cost analysis.

PURPOSE: To determine the impact of gynecologic magnetic resonance (MR) imaging on treatment decisions and net cost. MATERIALS AND METHODS: Sixty-nine consecutive women were referred for 70 pelvic MR imaging examinations. Diagnosis and treatment plans were obtained from referring physicians before and immediately after they were given verbal reports of MR imaging results. Outcome regarding treatment and symptoms was obtained at a mean follow-up of 10.9 months. RESULTS: Of 49 (71%) patients originally recommended for surgery, 36 (73%) either did not undergo surgery or less invasive surgery was performed. In 58 (84%) patients, the treatment performed was that recommended after performance of MR imaging. Symptoms resolved in 57 (83%) patients. Use of MR imaging resulted in an overall savings of $63 per patient ($1,736 per patient originally recommended for surgery). CONCLUSION: Use of pelvic MR imaging in diagnosis of some gynecologic diseases may alter treatment, decrease the number of invasive surgical procedures performed, and reduce total health care expenditures.

Pelvic phased array coil: image quality assessment for spin-echo MR imaging.

The NMR phased array coil (PA) provides improved signal-to-noise ratio (SNR) over that available with the body coil. We evaluated image quality obtained with a pelvic PA compared to that obtained with the body coil for spin-echo imaging. Thirty-three women undergoing clinical pelvic MRI were imaged with the body coil followed by imaging with the PA with the same field-of-view (FOV) in 11 patients, and with a small FOV in 23 patients. Image quality was assessed independently by two radiologists. In individual cases there was significant improvement in image quality with the PA, however the expected marked improvement in image quality was not consistently found. Two factors which may limit image quality are increased motion artifact and nonuniformity of signal with distance from the coils. Significant improvements in image quality may occur with improved techniques to decrease motion artifact.

Contrast agents for cardiac catheterization: conceptions and misconceptions.

Ionic and nonionic contrast materials are similarly efficacious in providing excellent images with minimal risk to the patient. In comparison with ionic media, the nonionic agents produce minor alterations in intracardiac and peripheral pressures as well as in electrocardiographic intervals and morphology. In addition, nonionic media are less often associated with undesirable symptoms, such as flushing and vomiting. At the same time, ionic and nonionic media are accompanied by a similar incidence of nephrotoxicity, serious arrhythmias, and death. Finally, nonionic contrast material is substantially more expensive than ionic media. In light of this marked difference in cost, one could argue that nonionic media should be reserved for "high-risk" patients, that is, those with a history of a serious adverse reaction to ionic contrast media and those in whom contrast-induced hypotension would be particularly deleterious.

Assessment of the sensitivity of hydrogen inhalation in the detection of left-to-right shunting.

For the detection of left-to-right intracardiac shunting, the oximetric and standard indocyanine green techniques are relatively insensitive, in that neither can reliably detect a shunt with a ratio of pulmonary to systemic flow (Qp/Qs) less than 1.3 (percentage shunt, 23%). Although the hydrogen inhalation method is said to be much more sensitive in this regard, no previous study has measured its sensitivity. Accordingly, in 15 patients (4 men, 11 women, aged 38 to 67 years) without intracardiac shunting, hydrogen inhalation was performed 1) without and 2) with an artificially created femoral arteriovenous shunt of known size, and cardiac output was measured by thermodilution. For the 15 subjects with cardiac outputs of 3.64 to 8.10 liters/min, shunts of 22 to 248 ml/min were created, so that the shunts ranged from 0.5% to 3.3%. Hydrogen inhalation detected all shunts greater than or equal to 1.3% (Qp/Qs greater than or equal to 1.01). Of the 10 shunts less than 1.3%, it detected 5, with the smallest being 0.7%. Thus, the hydrogen inhalation technique is extremely sensitive in identifying the presence of left-to-right shunting, far more sensitive than the oximetric and standard indocyanine green methods.