Outcomes of type 2 endoleaks detected on venous phase CT arteriography.

PURPOSE: The majority of type 2 endoleaks (T2EL) are identified on computed tomography angiography (CTA) both on arterial and venous phase. There is a subset of T2EL that are demonstrated only on venous phase CTA. This study was done to report the outcomes of T2EL detected only on venous phase CTA. MATERIALS AND METHODS: A total of 261 consecutive T2EL treated via embolization were reviewed for the presence of endoleak demonstrated only on venous phase CTA. A group of 16 patients (12 men, 4 women; mean age, 80.1 years) was identified who had pre-embolization venous phase T2EL. Patients were evaluated for presence of T2EL after embolization, change in aneurysm diameter, and need for further intervention. RESULTS: The prevalence of venous phase T2EL was 6.1% (16/261; 95%CI: 3.2%-9.0%). On post-embolization CTA, the rate of successful embolization at 6 months was 2/12 (17%; 95%CI: 0%-38%). At 6-month follow-up, mean change in aneurysm diameter was +2.3mm (n=12; 95%CI: -0.5mm to +5.0mm). In total, 4/16 (25%; 95%CI: 4%-46%) underwent re-embolization and 4/16 (25%, 95%CI: 4%-46%) underwent conversion to open repair. There was one aneurysm rupture, which was successfully treated surgically. CONCLUSION: These results suggest that venous phase T2EL are not as responsive to embolization as standard T2EL and emphasize the need to follow patients with venous phase T2EL closely.

Effect of elevated ammonia on tissue nitrogen metabolites in the ureotelic gulf toadfish (Opsanus beta) and the ammoniotelic midshipman (Porichthys notatus).

We investigated possible biochemical pathways explaining extreme ammonia tolerance by the gulf toadfish and specifically tested the prediction that the gulf toadfish Opsanus beta is more tolerant than the plainfin midshipman Porichthys notatus, two confamilial species, because it reverses brain glutamine accumulation during high ammonia exposure. This prediction stems from previous studies demonstrating that gulf toadfish produce urea from glutamine, a pathway not present in the ammoniotelic midshipman. Our results show that at the same water NH(3) concentration, ammonia increases more from control levels in brains of midshipman than toadfish. After 48 h of exposure to 50% of their respective LC(50) (96 h) value for ammonia, toadfish are able to return the ammonia-induced increase in brain glutamine back to control values, reducing brain glutamine by 2,500 micromol kg(-1). However, in midshipman, brain glutamine remains significantly elevated from control throughout the experiment. Toadfish exposed to 33% of their LC(50) (96 h) showed an initial increase in whole body urea, which is then reduced at a rate of 104 micromol kg fish(-1) h(-1) and could be directly excreted into the water. We discuss how the special handling of glutamine in toadfish may explain in part their great tolerance to ammonia.

The physiology and evolution of urea transport in fishes.

This review summarizes what is currently known about urea transporters in fishes in the context of their physiology and evolution within the vertebrates. The existence of urea transporters has been investigated in red blood cells and hepatocytes of fish as well as in renal and branchial cells. Little is known about urea transport in red blood cells and hepatocytes, in fact, urea transporters are not believed to be present in the erythrocytes of elasmobranchs nor in teleost fish. What little physiological evidence there is for urea transport across fish hepatocytes is not supported by molecular evidence and could be explained by other transporters. In contrast, early findings on elasmobranch renal urea transporters were the impetus for research in other organisms. Urea transport in both the elasmobranch kidney and gill functions to retain urea within the animal against a massive concentration gradient with the environment. Information on branchial and renal urea transporters in teleost fish is recent in comparison but in teleosts urea transporters appear to function for excretion and not retention as in elasmobranchs. The presence of urea transporters in fish that produce a copious amount of urea, such as elasmobranchs and ureotelic teleosts, is reasonable. However, the existence of urea transporters in ammoniotelic fish is curious and could likely be due to their ability to manufacture urea early in life as a means to avoid ammonia toxicity. It is believed that the facilitated diffusion urea transporter (UT) gene family has undergone major evolutionary changes, likely in association with the role of urea transport in the evolution of terrestriality in the vertebrates.

Glucocorticoid receptors are involved in the regulation of pulsatile urea excretion in toadfish.

The objectives of this study were to characterize the pattern of pulsatile urea excretion in the gulf toadfish in the wake of exogenous cortisol loading and to determine the receptors involved in the regulation of this mechanism. Toadfish were fitted with indwelling arterial catheters and were infused with isosmotic NaCl for 48 h after which fish were treated with cortisol alone, cortisol + peanut oil, cortisol + RU486 (a glucocorticoid receptor antagonist) or cortisol + spironolactone (a mineralocorticoid receptor antagonist). Upon cortisol loading, fish treated with cortisol alone, cortisol + oil or cortisol + spironolactone experienced a two- to threefold reduction in pulsatile urea excretion. This reduction was due to a decrease in urea pulse size with no effect on pulse frequency compared to values measured during the control NaCl infusion period. In addition, these fish showed an increase in plasma urea concentrations upon treatment. These apparent effects of cortisol treatment were abolished in fish treated with cortisol + RU486. In contrast, these fish showed an increase in pulsatile urea excretion mediated by a twofold increase in pulse size with no change in frequency. Likewise, fish treated with cortisol + RU486 showed a significant decrease in plasma urea concentrations over the course of the experiment. The findings of this study indicate that high levels of cortisol reduce pulsatile urea excretion by decreasing pulse size. In addition, it appears that glucocorticoid receptors and not mineralocorticoid receptors are involved in the regulation of the toadfish pulsatile urea excretion mechanism.

Effects of prolonged copper exposure in the marine gulf toadfish (Opsanus beta). I. Hydromineral balance and plasma nitrogenous waste products.

Acute (96 h) and prolonged (30 days) copper exposure induced osmoregulatory disturbance and impaired nitrogenous waste excretion in the marine teleost, the gulf toadfish (Opsanus beta), which was found to be extremely tolerant to acute copper exposure with a 96 h LC50 exceeding 340 microM but exhibited disturbed mineral balance in response to both acute and prolonged exposure to approximately 12 microM copper. The main cause of copper toxicity was found to be Na+ and Cl- regulatory failure leading to elevated plasma [Na+] and [Cl-] and osmolality which in turn led to fluid loss from muscle tissue. Analysis of intestinal fluid composition revealed a complicated pattern of effects of copper exposure. Intestinal transport physiology was directly influenced by copper exposure with Cl- absorption being the most sensitive parameter. Evidence for increased Na+ and fluid absorption when the fish exhibited elevated plasma osmolality indicates that the intestine may also exhibit a compensatory response to impairment of branchial transport processes, suggesting at least two target organs (gill and intestine) for copper toxicity in marine fish. Plasma Mg2+ was elevated from approximately 1.5 mM to as much as 4.0 mM, likely as a result of increased branchial permeability. While plasma [ammonia] clearly responded to copper exposure, plasma [urea] exhibited a much more sensitive and pronounced response to both acute and prolonged copper exposure, resulting in as much as a three-fold increase in circulating urea levels. This response is most likely the result of the unique ability of this teleost to convert ammonia to urea.

Effects of prolonged copper exposure in the marine gulf toadfish (Opsanus beta) II: copper accumulation, drinking rate and Na+/K+ -ATPase activity in osmoregulatory tissues.

Gulf toadfish were exposed to sublethal levels of copper (12.8 or 55.2 microM) for 30 days. Drinking in control fish averaged 1 ml kg(-1)h(-1) but exposure to 55.2 microM copper resulted in a complex biophasic pattern with initial (3 h and 1 day) inhibition of drinking rate, followed by an elevation of drinking rate from day 3 onwards. Drinking led to copper accumulation in the intestinal fluids at levels three to five times higher than the ambient copper concentrations, which in turn resulted in intestinal copper accumulation. The gill exhibited more rapid accumulation of copper than the intestine and contributed to early copper uptake leading to accumulation in internal organs. Muscle, spleen and plasma exhibited little if any disturbance of copper homeostasis while renal copper accumulation was evident at both ambient copper concentrations. The liver exhibited the highest copper concentrations and the greatest copper accumulation of all examined internal organs during exposure to 55.2 microM. Elevated biliary copper excretion was evident from measurements of gall bladder bile copper concentrations and appeared to protect partially against internal accumulation in fish exposed to 12.8 microM copper. No inhibition of Na+/K+ -ATPase activity in either gills or intestine was seen despite copper accumulation in these organs. Calculations of inorganic copper speciation suggest that Cu(CO3)(2)2- complexes which dominate in seawater and intestinal fluids are of limited availability for uptake while the low levels of ionic Cu2+, CuOH+ and CuCO3 may be the forms taken up by the gill and the intestinal epithelium.

The effect of chronic cortisol elevation on urea metabolism and excretion in the rainbow trout (Oncorhynchus mykiss).

The objective of this study was to investigate the possible involvement of cortisol in controlling urea metabolism and excretion in the ammoniotelic rainbow trout (Oncorhynchus mykiss). Trout fitted with dorsal aortic and internal urinary catheters received either no implant (control), or were implanted with coconut oil (sham), cortisol in coconut oil, RU486, a glucocorticoid receptor blocker, in coconut oil, or cortisol+RU486 in coconut oil, and monitored over 72 h. Rainbow trout treated with cortisol (+/- RU486) had similarly elevated plasma cortisol concentrations that were six fold greater than in control and sham fish. Elevated circulating cortisol concentrations caused a three-fold rise in plasma and urine urea concentrations, which was blocked by RU486. Similarly, a positive correlation between plasma cortisol and plasma urea concentrations was observed in fish treated with cortisol alone but not in fish treated with cortisol+RU486. Cortisol treatment caused an elevation in branchial (two fold higher) and urinary (three fold higher) excretion rates of urea compared to sham-implanted fish, which was prevented by treatment with RU486. However, as branchial and renal clearance were unaffected, there appears to be no stimulation or inhibition of urea excretion mechanisms in the gill or kidney separate from effects due to changes in plasma urea concentrations. Thus, cortisol and glucocorticoid receptors appear to be involved in the regulation of endogenous urea production but not in the control of urea excretory mechanisms in the ammoniotelic trout.

Branchial and renal excretion of urea and urea analogues in the plainfin midshipman, Porichthys notatus.

This study investigated whether urea transport mechanisms were present in the gills of the ammoniotelic plainfin midshipman (Porichthys notatus), similar to those recently documented in its ureotelic relative (family Batrachoididae), the gulf toadfish (Opsanus beta). Midshipmen were fitted with internal urinary and caudal artery catheters for repetitive sampling of urine and blood in experiments and radiolabeled urea analogues ([(14)C]-thiourea and [(14)C]-acetamide) were used to evaluate the handling of these substances. Isosmotically balanced infusions of urea were used to raise plasma and urine urea concentrations to levels surpassing physiological levels by 8.5-fold and 6.4-fold, respectively. Despite these high urea levels, there was no observable transport maximum in either renal or branchial urea excretion rate, a result mirrored by the total uptake of fish exposed to a range of environmental urea concentrations. Permeability to urea appeared to be symmetrical in the two directions. At comparable plasma concentrations the branchial clearance rate of acetamide was 74% that of urea while branchial clearance rate of thiourea was 55% that of urea. For influx, the comparable values were 60% and 36%, indicating the same pattern. In contrast, the secretion clearance rate of acetamide by the kidney was 56% that of urea while the rate of thiourea secretion clearance was 137% greater than that of urea, with both urea and thiourea being more concentrated in the urine than in the plasma. In addition, the secretion clearance rates of thiourea and urea were significantly greater than those of water and Cl(-), whereas acetamide, water and Cl(-) were found equally in the plasma and urine, appearing to passively equilibrate between the two fluids. Based on our findings, there appear to be two distinct transport mechanisms involved in urea excretion in the plainfin midshipmen, one in the gill (a facilitated diffusion type transporter) and one in the kidney (an active transport mechanism), each of which does not saturate even at plasma urea concentrations that greatly exceed physiological levels. These transporters appear to be similar to those in the midshipman's ureotelic relative, the gulf toadfish.

Do circulating plasma AVT and/or cortisol levels control pulsatile urea excretion in the gulf toadfish (Opsanus beta)?

Previous work has shown that pulsatile urea excretion at the gills of the gulf toadfish is due to periodic activation of a facilitated diffusion transport system with molecular and pharmacological similarity to the UT-A transport system of the mammalian kidney. In mammals, AVP and glucocorticoids are two important endocrine regulators of this system. The present study focused on the potential role of circulating AVT (the teleost homologue of AVP) and cortisol levels as possible triggers for urea pulses. Long-term (34-84 h) monitoring of plasma levels by repetitive sampling at 2-h intervals from chronic cannulae in individual toadfish demonstrated that circulating AVT concentrations are low (10(-12)-10(-11) M), and show no relationship to the occurrence of natural urea pulses. In contrast, plasma cortisol levels decline greatly prior to natural pulses and rise rapidly thereafter. AVT injections into the caudal artery or ventral aorta elicited pulse events, but these were extremely small (1-10%) relative to natural pulses, and occurred only at unphysiological dose levels (10(-9) M in the plasma). AVP was a partial agonist, but isotocin, insulin-like growth factor-1, and atrial natriuretic peptide were without effect at the same concentration. Artificially raising plasma cortisol levels by cortisol injection tended to reduce responsiveness to AVT. Pharmacological reduction of plasma cortisol levels by metyrapone injection elicited small pulses similar to those caused by AVT. Following such pulse events, AVT was ineffective in inducing pulses. We conclude that decreases in circulating cortisol play an important permissive role in urea pulsing, but that circulating AVT levels are not involved.

The hospitalist movement: wise or wishful thinking?

One-third of all health care expenditures--nearly 5% of the gross domestic product--relates to hospital care. Can hospitalists provide the financial solution?

Differential branchial and renal handling of urea, acetamide and thiourea in the gulf toadfish Opsanus beta: evidence for two transporters.

The possible presence of a urea transporter in the kidney of the gulf toadfish (Opsanus beta) and further characterization of the pulsatile facilitated transporter previously identified in its gills were investigated by comparing the extra-renal and renal handling of two urea analogues with the handling of urea. Toadfish were fitted with caudal artery and indwelling urinary ureteral catheters and injected with an iso-osmotic dose of (14)C-labelled urea analogue (acetamide or thiourea) calculated to bring plasma analogue concentrations close to plasma urea concentrations. Branchial permeabilities to urea, acetamide and thiourea were similar during non-pulsing periods and all increased during pulse events, although urea permeability was greater than analogue permeability during pulses. The incidence and magnitude of acetamide and urea pulses at the gills were significantly correlated, acetamide pulses being 35-50 % of the size of urea pulses. However, the thiourea and urea pulses at the gills were only weakly correlated, thiourea pulses being less than 16 % of the size of urea pulses. Thiourea inhibited branchial urea excretion by reducing the pulse frequency. The renal handling of thiourea and urea were similar in that both substances were more concentrated in the urine than in the plasma, whereas acetamide was found in equal concentrations in the urine and plasma. Urea and thiourea were secreted 2-3 times more effectively than Cl(-) and water, whereas acetamide was secreted at a similar relative rate. The differential handling of the urea analogues by the gills and kidney indicates the presence of a different, possibly unique, transporter in the kidney. The movement of thiourea and urea into the renal tubule against an apparent concentration gradient suggests the presence of an active transport mechanism.

Distinguishing wear and creep in clinically retrieved polyethylene inserts.

There is an increasing awareness of the clinical problems associated with ultra-high-molecular-weight polyethylene (UHMWPE) wear and failure in orthopedics. To better understand the reasons for wear and failure, methods were developed using polarized light microscopic analysis and backscattered electron (BSE) imaging with correlated elemental analysis to distinguish the contributions of wear, creep, and third-body particulate. This study determined that microscopic metal particles (< 10 microns) previously not observed with the stereomicroscope could be easily observed with the BSE technique. BSE imaging identified embedded metal in 5/5 of the tibial and 2/4 of the acetabular inserts, which were thought to be free of metal debris after stereoscopic examination. Correlated elemental analysis showed that the microscopic particles could be traced to the elements known to be present in the porous coatings of the retrieved uncemented implants. Creep was distinguished from wear in the total hip and total knee inserts by using polarized light microscopic techniques. Continued development of polarized light microscopic techniques applied in this investigation should assist biomaterials experts in the future to better distinguish wear and creep in retrieved clinical inserts. The correlated BSE and elemental analysis will assist in determining the roll of microscopic third-body particular in wear and osteolysis in total joint replacement.

HOT: the emergence of health oriented telecommunication applications.

America has benefited from decades of outstanding health services. However, the American health system now is in crisis--with runaway medical cost inflation, hospital closures, and unacceptably high and increasing numbers of uninsured people. Key solutions for bringing the health system into balance remain untapped in the potentials of health-oriented telecommunication, or HOT applications. HOT applications could rally the immense unused personal resources of the public for improving their own health, help upgrade the delivery and efficiency of healthcare and its administration, and improve public health's ability to deal with present and emerging system-level problems impacting health.