Transformation and release of micronized Cu used as a wood preservative in treated wood in wetland soil.

Micronized Cu (µ-Cu) is used as a wood preservative, replacing toxic chromated copper arsenate (CCA). Micronized Cu is malachite [Cu2CO3(OH)2] that has been milled to micron/submicron particles, with many particle diameters less than 100 nm, mixed with biocides and then used to treat wood. In addition to concerns about the fate of the Cu from µ-Cu, there is interest in the fate of the nano-Cu (n-Cu) constituents. We examined movement of Cu from µ-Cu-treated wood after placing treated-wood stakes into model wetland ecosystems. Release of Cu into surface and subsurface water was monitored. Surface water Cu reached maximum levels 3 days after stake installation and remained elevated if the systems remained inundated. Subsurface water Cu levels were 10% of surface water levels at day 3 and increased gradually thereafter. Sequential filtering indicated that a large portion of the Cu in solution was associating with soluble organics, but there was no evidence for n-Cu in solution. After 4 months, Cu in thin-sections of treated wood and adjacent soil were characterized with micro X-ray absorption fine structure spectroscopy (µ-XAFS). Localization and speciation of Cu in the wood and adjacent soil using µ-XAFS clearly indicated that Cu concentrations decreased over time in the treated wood and increased in the adjacent soil. However, n-Cu from the treated wood was not found in the adjacent soil or plant roots. The results of this study indicate that Cu in the µ-Cu-treated wood dissolves and migrates into adjacent soil and waters primarily in ionic form (i.e., Cu2+) and not as nano-sized Cu particles. A reduced form of Cu (Cu2S) was identified in deep soil proximal to the treated wood, indicating strong reducing conditions. The formation of the insoluble Cu2S effectively removes some portion of dissolved Cu from solution, reducing movement of Cu2+ to the water column and diminishing exposure.

Systemic ventricular assist device support in Fontan patients: A report by ACTION.

BACKGROUND: The size of the Fontan population with end-stage heart failure is growing. In this population, heart transplantation has been the only option. This study sought to investigate the efficacy of ventricular assist device (VAD) support in Fontan patients. METHODS: We conducted a retrospective study of Fontan patients in the Advanced Cardiac Therapies Improving Outcomes Network. We evaluated patient characteristics, and the clinical and physiologic outcomes after VAD implantation. RESULTS: We identified 45 Fontan patients implanted with VAD. The average age of patients was 10 years (interquartile range: 4.5-18) and 30% were female. The majority had a morphologic right ventricle (69%), moderate or greater ventricular dysfunction (83%), and moderate or greater atrioventricular valve regurgitation (65%). The majority of implants were as a bridge to transplantation (76%), and the majority of patients were Interagency Registry for Mechanically Assisted Circulatory Support Profile 2 (56%). The most commonly employed device was the Medtronic HeartWare HVAD (56%). A total of 13 patients were discharged on device support, and 67% of patients experienced adverse events, the most common of which were neurologic (25%). At 1 year after device implantation, the rate of transplantation was 69.5%, 9.2% of patients continued to be VAD supported, and 21.3% of patients had died. Hemodynamically, VAD was effective in decreasing both Fontan and ventricular end-diastolic pressures in some individuals. CONCLUSIONS: VAD is effective in supporting patients with end-stage Fontan failure awaiting heart transplantation. Future research should focus on identifying clinical and physiologic characteristics predictive of a favorable response to VAD support.

Intracerebral and subarachnoid hemorrhage in patients with cancer.

OBJECTIVE: To analyze the risk factors, presentation, etiologies, and outcomes of adult cancer patients with intracranial hemorrhage (IH). METHODS: We analyzed 208 patients retrospectively with the diagnosis of IH from the Memorial Sloan-Kettering neurology database from January 2000 through December 2007. Charts were examined for clinical and radiographic data. Survival was calculated using the Kaplan-Meier method. Survival between groups was compared via the log-rank test. Logistic regression models were used to assess for prognostic indicators of 30- and 90-day mortality. RESULTS: There were 181 intracerebral and 46 subarachnoid hemorrhages. Sixty-eight percent of patients had solid tumors, 16% had primary brain tumors, and 16% had hematopoietic tumors. Hemiparesis and headache were the most common symptoms. Intratumoral hemorrhage (61%) and coagulopathy (46%) accounted for the majority of hemorrhages, whereas hypertension (5%) was rare. Median survival was 3 months (95% confidence interval [CI] 2-4), and 30-day mortality was 31%. However, nearly one-half of patients were completely or partially independent at the time of discharge. Patients with primary brain tumors had the longest median survival (5.9 months, 95% CI 2.9-11.8, p = 0.05). Independent predictors of 30-day mortality were not having a primary brain tumor, impaired consciousness, multiple foci of hemorrhage, hydrocephalus, no ventriculostomy, and treatment of increased intracranial pressure. CONCLUSIONS: Intracranial hemorrhage in patients with cancer is often due to unique mechanisms. Prognosis is poor, but comparable to intracranial hemorrhage in the general population. Aggressive care is recommended despite high mortality, because many patients have good functional outcomes.

Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo.

The constitutive cyclooxygenase (COX)-1 enzyme has been considered the physiologically important isoform for prostaglandin synthesis in the normal kidney. It has, therefore, been suggested that selective inhibitors of the 'inducible' isoform (COX-2) may be free from renal adverse effects. We studied the renal effects of the predominantly COX-2 antagonist nabumetone in isolated perfused kidneys. As compared with controls, kidneys removed after in vivo administration of oral nabumetone (15 mg/kg) disclosed altered renal function with reduced glomerular filtration rate, filtration fraction, and urine volume and enhanced hypoxic outer medullary tubular damage. By contrast, renal function and morphology were not affected in vivo by nabumetone or its active metabolite 6-methoxy-2-naphthylacetic acid. The latter agent (10-20 mg/kg i.v.) did not significantly alter renal microcirculation, as opposed to a selective substantial reduction in medullary blood flow noted with the nonselective COX inhibitor indomethacin (5 mg/kg i.v.). In a rat model of acute renal failure, induced by concomitant administration of radiocontrast, nitric oxide synthase, and COX inhibitors, the decline in kidney function and the extent of hypoxic medullary damage with oral nabumetone (80 mg/kg) were comparable to a control group, and significantly less than those induced by indomethacin. In rats subjected to daily oral nabumetone for 3 consecutive weeks, renal function and morphology were preserved as well. Both nabumetone and 6-methoxy-2-naphthylacetic acid reduced renal parenchymal prostaglandin E2 to the same extent as indomethacin. It is concluded that while nabumetone adversely affects renal function and may intensify hypoxic medullary damage ex vivo, rat kidneys are not affected by this agent in vivo, both in acute and chronic studies. COX selectivity may not explain the renal safety of nabumetone.

An optimized probe set for the detection of small interchromosomal aberrations by use of 24-color FISH.

The rapid spread of the use of new 24-color karyotyping techniques has preceded their standardization. This is best documented by the fact that the exact resolution limits have not yet been defined. Indeed, it is shown here that a substantial proportion of interchromosomal aberrations will be missed by all multicolor karyotyping systems currently in use. We demonstrate that both the sensitivity and the specificity of 24-color karyotyping critically depend on the fluorochrome composition of chromosomes involved in an interchromosomal rearrangement. As a solution, we introduce a conceptual change in probe labeling. Seven-fluorochrome sets that overcome many of the current limitations are described, and examples of their applications are shown. The criteria presented here for an optimized probe-set design and for the estimation of resolution limits should have important consequences for pre- and postnatal diagnostics and for research applications.

Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia.

Recent experimental data underlies the role of hypoxic tubular injury in the pathophysiology of radiocontrast nephropathy. Although systemic transient hypoxemia, increased blood viscosity, and a leftward shift of the oxygen-hemoglobin dissociation curve may all contribute to intrarenal hypoxia, imbalance between oxygen demand and supply plays a major role in radiocontrast-induced outer medullary hypoxic damage. Low oxygen tension normally exists in this renal region, reflecting the precarious regional oxygen supply and a high local metabolic rate and oxygen requirement, resulting from active salt reabsorption by medullary thick ascending limbs of Henle's loop. Radiologic contrast agents markedly aggravate outer medullary physiologic hypoxia. This results from enhanced metabolic activity and oxygen consumption (as a result of osmotic diuresis and increased salt delivery to the distal nephron) because the regional blood flow and the oxygen supply actually increase. The latter effect may result in part from the activation of various regulatory mediators of outer medullary blood flow to ensure maximal regional oxygen supply. Low-osmolar radiocontrast agents may be less nephrotoxic because of the smaller osmotic load and vasomotor alterations. Experimental radiocontrast-induced renal failure requires preconditioning of animals with various insults (for example, congestive heart failure, reduced renal mass, salt depletion, or inhibition of nitric oxide and prostaglandin synthesis). In all these perturbations, which resemble clinical conditions that predispose to contrast nephropathy, outer medullary hypoxic injury results from insufficiency or inactivation of mechanisms designed to preserve regional oxygen balance. This underlines the importance of identifying and ameliorating predisposing factors in the prevention of this iatrogenic disease.

Likelihood ratios: getting diagnostic testing into perspective.

In modern medicine, sophisticated laboratory tests and imaging studies are often emphasized at the expense of history and physical examination, rather than complementing clinical assessment. Ancillary testing often fails to advance the diagnostic process, and increases patient risk and the expense of medical care. The relative value of clinical evaluation and technological methods is rarely considered, and the power of the clinical evaluation is therefore underestimated. The likelihood ratio (LR) is a semiquantitative measure of the performance of diagnostic tests which indicates how much a diagnostic procedure modifies the probability of disease, and is calculated from the sensitivity and specificity of the test (or directly from the change in probability associated with the test result). We review the performance of frequently-used tests by their LRs, and compare them to the power of clinical assessment, with clinical cases to illustrate the application of LRs in the diagnostic process. The discriminative power of clinical assessment and ancillary tests is often similar, and the combination of the two greatly increases accuracy in the diagnostic process. Clinical assessment is indeed frequently more informative than current technical modalities. LRs assist in putting the value of testing in proper perspective. Practice in evaluating pre-test probabilities of disease and in the application of LRs should be enhanced in medical training.

Frontal lobe shortening in second-trimester fetuses with trisomy 21: usefulness as a US marker.

PURPOSE: To determine whether the frontal lobe is disproportionately smaller than normal in second-trimester fetuses with Down syndrome by using prenatal ultrasonographic (US) measurements of the frontothalamic distance (FTD). MATERIALS AND METHODS: The FTD, measured from the inner table of the frontal bone to the posterior margin of the thalamus, was measured in 43 fetuses (mean gestational age, 17.2 weeks +/- 1.3 [standard deviation]; range, 15.0-20.4 weeks) with chromosomally proved trisomy 21 and in 160 chromosomally normal fetuses (mean gestational age, 17.1 weeks +/- 1.5; range, 14.5-22.5 weeks). Other cranial biometric ratios also were calculated. RESULTS: The FTD was best predicted from the estimated gestational age (EGA) in the euploid population with the quadratic equation FTD = -0.0120 x EGA2 + 0.6917 x EGA - 5.2349 (R2 = .731) or from the biparietal diameter (BPD) with the linear equation FTD = 0.6837 x BPD + 0.5525 (R2 = .731). If an observed-to-expected ratio of 0.84 is used as a cutoff sign to screen for trisomy 21, a sensitivity of 16%, specificity of 97%, odds ratio of 6.03 (95% confidence interval, 1.81, 20.1), and relative risk of 5.98 are achieved. CONCLUSION: The frontal lobe is statistically significantly smaller in fetuses with trisomy 21. US measurement of the FTD may prove to be a useful adjunctive screening tool if used with other markers for Down syndrome.

Bradycardia in toluene poisoning.

BACKGROUND: Tachyarrhythmias are the classical manifestation of toluene cardiotoxicity. The presumed mechanism is sensitization of the myocardium to the potential arrhythmogenic effect of endogenous catecholamines, occasionally resulting in fatality. Bradyarrhythmias have been repeatedly shown in animal models, but have been reported only once in a human. CASE REPORTS: Two patients with toluene intoxication presented with severe sinus bradycardia. One patient had also atrial-ventricular dissociation. In both cases cardiac rhythm returned to normal within several hours. CONCLUSION: We suggest that the spectrum of cardiotoxic symptoms associated with toluene intoxication in humans includes bradyarrhythmias as well as tachyarryhthmias.

Precipitating events, locations and reactions associated with initial unexpected panic attacks.

This study examined the phenomenology of the initial panic attack in 85 panic disorder patients with or without agoraphobia. Patients were divided into minimal and extensive avoiders and three domains were assessed: precipitating factors, location of initial panic, and reaction to the panic. No apparent precipitating factor could be identified in approx 40% of the patients. The most common precipitants were injury/illness and interpersonal conflict. Extensive avoiders were more likely to have experienced the initial panic in classic agoraphobic situations. Public transportation was the most common location for the total sample. In reaction to the panic, minimal avoiders were more likely to have gone to a hospital emergency room (ER) whereas extensive avoiders were more likely to have done nothing in terms of help-seeking. Many patients with either minimal or extensive avoidance avoided the locations where the initial panic occurred, suggesting that circumscribed avoidance does not always generalize.

New models for PA advancement. Forum discussion.

Many PAs are grappling with the problem of how to best advance their careers. In this roundtable, the participants discuss traditional methods of advancement and examine the need for new models.