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Screening for chronic kidney disease is recommended in people at high risk, but data on the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with all-cause and cardiovascular mortality are limited. To clarify this, we performed a collaborative meta-analysis of 10 cohorts with 266,975 patients selected because of increased risk for chronic kidney disease, defined as a history of hypertension, diabetes, or cardiovascular disease. Risk for all-cause mortality was not associated with eGFR between 60-105 ml/min per 1.73 m², but increased at lower levels. Hazard ratios at eGFRs of 60, 45, and 15 ml/min per 1.73 m² were 1.03, 1.38 and 3.11, respectively, compared to an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log risk for all-cause mortality without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 10, 30 and 300 mg/g were 1.08, 1.38, and 2.16, respectively compared to a ratio of five. Albuminuria and eGFR were multiplicatively associated with all-cause mortality, without evidence for interaction. Similar associations were observed for cardiovascular mortality. Findings in cohorts with dipstick data were generally comparable to those in cohorts measuring albumin-to-creatinine ratios. Thus, lower eGFR and higher albuminuria are risk factors for all-cause and cardiovascular mortality in high-risk populations, independent of each other and of cardiovascular risk factors.

Polygyny and extra-pair paternity are generally thought to enhance sexual selection. However, the extent to which these phenomena increase variance in male reproductive success will depend on the covariance between success at these two strategies. We analysed these patterns over four breeding seasons in facultatively polygynous blue tits Cyanistes caeruleus. We found that both polygyny and extra-pair paternity increased variance in male reproductive success and that standardised variance in annual number of genetic fledglings was 2.6 times higher than standardised variance in apparent success when assuming strict monogamy. Nevertheless, male success at securing within-pair paternity was unrelated to success at gaining extra-pair paternity and, when considering the positive effect of age on extra-pair success and attracting a second female, polygynous males were no more likely to sire extra-pair fledglings. Overall, polygynous males fledged more genetic offspring than monogamous males, but first-year polygynous males lost a greater share of within-pair paternity. A literature review suggests that this adverse effect of polygyny on within-pair paternity is frequent among birds, inconsistent with the prediction that females engage in extra-pair copulation with successful males to obtain good genes. Furthermore, a male's share of paternity was repeatable between years, and among females of polygynous males within years, such that a compatibility function of extra-pair copulations was likewise unsupported. Instead, we suggest that the observed patterns are most consistent with a fertility insurance role for extra-pair copulations, which does not exclude the greater opportunity for sexual selection through differential ability of males to gain paternity.

In most monogamous bird species, circulating testosterone concentration in males is elevated around the social female's fertile period. Variation in elevated testosterone concentrations among males may have a considerable impact on fitness. For example, testosterone implants enhance behaviours important for social and extra-pair mate choice. However, little is known about the relationship between natural male testosterone concentration and sexual selection. To investigate this relationship we measured testosterone concentration and sexual signals (ventral plumage colour and tail length), and determined within and extra-pair fertilization success in male North American barn swallows (Hirundo rustica erythrogaster). Dark rusty coloured males had higher testosterone concentrations than drab males. Extra-pair paternity was common (42% and 31% of young in 2009 and 2010, respectively), but neither within- nor extra-pair fertilization success was related to male testosterone concentration. Dark rusty males were less often cuckolded, but did not have higher extra-pair or total fertilization success than drab males. Tail length did not affect within- or extra-pair fertilization success. Our findings suggest that, in North American barn swallows, male testosterone concentration does not play a significant direct role in female mate choice and sexual selection. Possibly plumage colour co-varies with a male behavioural trait, such as aggressiveness, that reduces the chance of cuckoldry. This could also explain why dark males have higher testosterone concentrations than drab males.

Background and Objectives: This study investigates whether the association between estimated GFR (eGFR) and cardiovascular (CV) outcome differs for different measures of eGFR and different age groups., Design, Setting, Participants, & Measurements: Between 1997 and 1998, 8047 participants visited our outpatient clinic for measurement of serum creatinine, serum cystatin C, urinary creatinine, and urinary albumin excretion. GFR was estimated by the Modification of Diet in Renal Disease formula, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, a cystatin C-based formula, a formula combining serum creatinine and cystatin C, and 24-hour creatinine clearance. Subjects had follow-up on CV events until 2005., Results: During follow-up, 530 subjects had a CV event. The association between eGFR and CV events was significantly modified by age, except when GFR was estimated by 24-hour creatinine clearance. In subjects <60 years of age, all measures of eGFR were independently and significantly associated with CV events, whereas in subjects ≥60 years of age only 24-hour creatinine clearance had a weak but significant association with CV events. For all measures and all levels of eGFR, subjects with elevated levels of albuminuria were at higher risk of CV events compared with subjects with normoalbuminuria., Conclusions: In the general population, all measures of eGFR are independently and significantly associated with CV events in individuals <60 years of age, but in subjects ≥60 years of age, only 24-hour creatinine clearance is. In general, the association between eGFR and risk of CV events is weaker in elderly subjects than in younger subjects.

Engagement in extra-pair copulations is an example of the abundant conflicting interests between males and females over reproduction. Potential benefits for females and the risk of cuckoldry for males are expected to have important implications on the evolution of parental care. However, whether parents adjust parental care in response to parentage remains unclear. In Eurasian penduline tits Remiz pendulinus, which are small polygamous songbirds, parental care is carried out either by the male or by the female. In addition, one third of clutches is deserted by both male and female. Desertion takes place during the egg-laying phase. Using genotypes of nine microsatellite loci of 443 offspring and 211 adults, we test whether extra-pair paternity predicts parental care. We expect males to be more likely to desert cuckolded broods, whereas we expect females, if they obtain benefits from having multiple sires, to be more likely to care for broods with multiple paternity. Our results suggest that parental care is not adjusted to parentage on an ecological timescale. Furthermore, we found that male attractiveness does not predict cuckoldry, and we found no evidence for indirect benefits for females (i.e., increased growth rates or heterozygosity of extra-pair offspring). We argue that male Eurasian penduline tits may not be able to assess the risk of cuckoldry; thus, a direct association with parental care is unlikely to evolve. However, timing of desertion (i.e., when to desert during the egg-laying phase) may be influenced by the risk of cuckoldry. Future work applying extensive gene sequencing and quantitative genetics is likely to further our understanding of how selection may influence the association between parentage and parental care.

In many socially monogamous animals, females engage in extrapair copulation (EPC), causing some broods to contain both within-pair and extrapair young (EPY). The proportion of all young that are EPY varies across populations and species. Because an EPC that does not result in EPY leaves no forensic trace, this variation in the proportion of EPY reflects both variation in the tendency to engage in EPC and variation in the extrapair fertilization (EPF) process across populations and species. We analyzed data on the distribution of EPY in broods of four passerines (blue tit, great tit, collared flycatcher, and pied flycatcher), with 18,564 genotyped nestlings from 2,346 broods in two to nine populations per species. Our Bayesian modeling approach estimated the underlying probability function of EPC (assumed to be a Poisson function) and conditional binomial EPF probability. We used an information theoretical approach to show that the expected distribution of EPC per female varies across populations but that EPF probabilities vary on the above-species level (tits vs. flycatchers). Hence, for these four passerines, our model suggests that the probability of an EPC mainly is determined by ecological (population-specific) conditions, whereas EPF probabilities reflect processes that are fixed above the species level.

Background: Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality., Methods: In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders., Findings: The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements., Interpretation: eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease., Funding: Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Species that pass repeatedly through narrow population bottlenecks (<100 individuals) are likely to have lost a large proportion of their genetic variation. Having genotyped 92 Raso larks Alauda razae, a Critically Endangered single-island endemic whose world population in the Cape Verdes over the last 100 years has fluctuated between about 15 and 130 pairs, we found variation at 7 of 21 microsatellite loci that successfully amplified, the remaining loci being monomorphic. At 6 of the polymorphic loci variation was sex-linked, despite the fact that these microsatellites were not sex-linked in the other passerine birds where they were developed. Comparative analysis strongly suggests that material from several different autosomes has been recently transferred to the sex chromosomes in larks. Sex-linkage might plausibly allow some level of heterozygosity to be maintained, even in the face of persistently small population sizes.

Using the wind-dispersed plant Mycelis muralis, we examined how landscape fragmentation affects variation in seed traits contributing to dispersal. Inverse terminal velocity (Vt(-1)) of field-collected achenes was used as a proxy for individual seed dispersal ability. We related this measure to different metrics of landscape connectivity, at two spatial scales: in a detailed analysis of eight landscapes in Spain and along a latitudinal gradient using 29 landscapes across three European regions. In the highly patchy Spanish landscapes, seed Vt(-1)increased significantly with increasing connectivity. A common garden experiment suggested that differences in Vt(-1) may be in part genetically based. The Vt(-1) was also found to increase with landscape occupancy, a coarser measure of connectivity, on a much broader (European) scale. Finally, Vt(-1)was found to increase along a south-north latitudinal gradient. Our results for M. muralis are consistent with 'Darwin's wind dispersal hypothesis' that high cost of dispersal may select for lower dispersal ability in fragmented landscapes, as well as with the 'leading edge hypothesis' that most recently colonized populations harbour more dispersive phenotypes.

The explanation for extra-pair mating in female birds remains poorly understood and contentious [1-7]. Several leading hypotheses propose that females benefit indirectly by enhancing the genetic quality of their offspring, through good genes or genetic compatibility effects [1, 8, 9]. Supporting this idea, recent studies have identified a range of fitness-related traits for which extra-pair offspring (EPO) are superior to their within-pair (WP) half-siblings [10-21]. However, such performance differences may result from nongenetic maternal effects if EPO are positioned earlier in the laying order and benefit from the advantages of earlier hatching [22, 23]. Here we show that EPO are larger, heavier, and more likely to fledge than their WP half-siblings in a population of blue tits, Cyanistes caeruleus. However, extra-pair paternity declined markedly with laying order, resulting in EPO generally hatching earlier. After correcting for variation in hatch time, none of the observed disparities between EPO and their WP half-siblings remained significant. These findings indicate that phenotypic comparisons between maternal half-siblings must consider potential hatching-order effects and suggest that the evidence for genetic benefits from extra-pair copulation may be less compelling than currently accepted. Moreover, the overrepresentation of EPO early in the laying order may help explain female extra-pair mating.

It is unknown whether screening for albuminuria in the general population identifies individuals at increased risk for renal replacement therapy (RRT) or accelerated loss of renal function. Here, in a general population-based cohort of 40,854 individuals aged 28 to 75 yr, we collected a first morning void for measurement of urinary albumin. In a subset of 6879 individuals, we measured 24-h urinary albumin excretion and estimated GFR at baseline and during 6 yr of follow-up. Linkage with the national RRT registry identified 45 individuals who started RRT during 9 yr of follow-up. The quantity of albuminuria was associated with increased renal risk: the higher the level of albuminuria, the higher the risk of need for renal replacement therapy and the more rapid renal function decline. A urinary albumin concentration of > or =20 mg/L identified individuals who started RRT during follow-up with 58% sensitivity and 92% specificity. Of the identified individuals, 39% were previously unknown to have impaired renal function, and 50% were not being medically treated. Restricting screening to high-risk groups (e.g., known hypertension, diabetes, cardiovascular disease [CVD], older age) reduced the sensitivity of the test only marginally but failed to identify 45% of individuals with micro- and macroalbuminuria. In conclusion, individuals with elevated levels of urinary albumin are at increased risk for RRT and accelerated loss of renal function. Screening for albuminuria identifies patients at increased risk for progressive renal disease, 40 to 50% of whom were previously undiagnosed or untreated.

1. An increase of competition among adults or nestlings usually negatively affects breeding output. Yet little is known about the differential effects that competition has on the offspring sexes. This could be important because it may influence parental reproductive decisions. 2. In sexual size dimorphic species, two main contradictory mechanisms are proposed regarding sex-specific effects of competition on nestling performance assuming that parents do not feed their chicks differentially: (i) the larger sex requires more resources to grow and is more sensitive to a deterioration of the rearing conditions ('costly sex hypothesis'); (ii) the larger sex has a competitive advantage in intra-brood competition and performs better under adverse conditions ('competitive advantage hypothesis'). 3. In the present study, we manipulated the level of sex-specific sibling competition in a great tit population (Parus major) by altering simultaneously the brood size and the brood sex ratio on two levels: the nest (competition for food among nestlings) and the woodlot where the parents breed (competition for food among adults). We investigated whether altered competition during the nestling phase affected nestling growth traits and survival in the nest and whether the effects differed between males, the larger sex, and females. 4. We found a strong negative and sex-specific effect of experimental brood size on all the nestling traits. In enlarged broods, sexual size dimorphism was smaller which may have resulted from biased mortality towards the less competitive individuals i.e. females of low condition. No effect of brood sex ratio on nestling growth traits was found. 5. Negative brood size effects on nestling traits were stronger in natural high-density areas but we could not confirm this experimentally. 6. Our results did not support the 'costly sex hypothesis' because males did not suffer from higher mortality under harsh conditions. The 'competitive advantage hypothesis' was also not fully supported because females did not suffer more in male-biased broods. 7. We conclude that male nestlings are not likely to be more expensive to raise, yet they have a size-related competitive advantage in large broods, leading to higher mortality of their on average lighter female nest mates.

This review discusses various screening approaches for chronic kidney disease that are used in Europe. The criterion for defining chronic kidney disease in the various programs differs but is frequently limited to estimated glomerular filtration rate, thus offering only data on chronic kidney disease stages 3 and higher; however, screening should not be limited to measuring only estimated glomerular filtration rate but should also include a measure of microalbuminuria, because this will offer identification of chronic kidney disease stages 1 and 2. Defining these earlier stages is of importance because the risk for developing end-stage renal disease that is associated with stages 1 and 2 is nearly equal to the risk that is associated with stage 3. Moreover, the risk for cardiovascular events in stages 1 and 2 is equal to that in stage 3. Various reports argue that costs of screening programs in general practitioner or outpatient offices are high and that they are cost-effective only for preventing end-stage renal disease when they are limited to target groups, such as patients with diabetes or hypertension and elderly. The benefits of screening programs, however, should not be evaluated only with respect to the prevention of renal events but should also include the benefits of preventing cardiovascular events. The use of preselection based on either an impaired estimated glomerular filtration rate or on protein-dipstick positivity or elevated albuminuria in a morning urine void has been found effective in various European countries as an alternative for targeted screening.

A consequence of gastrectomy is loss of bone mass. Several mechanisms have been proposed, such as malabsorption of vitamins and minerals. Additionally, a peptide hormone produced in the stomach has been shown to mediate a calcitropic effect on bone. The identity of this peptide has not been elucidated, but ghrelin, produced by A-like cells in the fundus of the stomach, could be a good candidate. Ghrelin stimulates growth hormone (GH) secretion both in vivo and in vitro, and could by this means have a positive effect on bone. There is also evidence for direct effects of ghrelin on bone. We discuss here the role that ghrelin may play in bone metabolism, based on the most recent literature.

Acute wounds which cannot be closed primarily are usually closed with a split skin graft. However a split skin graft has both functional (where tendons are exposed) and esthetic sequelae (contour deformity, different skin in color and texture). A novel technique is described which allows delayed primary closure of either fasciotomy wounds or full-thickness defects after harvest of a free or pedicle flap. The technique described combines the bootlace suture technique (which achieves wound closure by progressive suture tightening) with the VAC (vacuum-assisted closure) system (which reduces tissue edema, facilitating movement of tissue, and also reduces bacterial contamination of the wound). Twelve of 14 wounds (average width of wound after insertion and tightening of bootlace suture was 5 cm) were successfully closed after an average of 8 days (range, 4-23 days) in 11 patients (mean age, 45 years; range, 18-77 years) using this technique. Of the 2 patients where the technique was not successful, one patient was noncompliant and the other developed wound-edge necrosis. Other complications were self-limiting. The combined use of 2 methods of wound management facilitates delayed primary wound closure.

Background: Post-transplant diabetes (PTDM) is a common and serious complication of kidney transplantation. The implications of developing hyperglycemia of lesser severity are not well understood., Methods: In this study we used American Diabetes Association (ADA) criteria to assess the incidence of abnormal glycemia post-transplant, the variables that relate to this complication, and the relationship between hyperglycemia and cardiovascular (CV) disease. Included in the study were 490 kidney recipients, transplanted from 1998 to 2003, without a history of diabetes, and with a pretransplant fasting glucose <126 mg/dL., Results: Within one week post-transplant, 45% of recipients had impaired fasting glycemia (IFG, glucose 100-125 mg/dL), and 21% PTDM (glucose > or =126). One year post-transplant, 33% of patients had IFG, and 13% PTDM. Risk factors for hyperglycemia at one year included: older recipient, male gender, higher BMI, higher pretransplant glucose, and higher glucose one week post-transplant (all P < 0.002 by multivariable analyses). During a follow-up period of 40 +/- 14 months, 12% of recipients had CV events (cardiac, CVA, and/or peripheral). Increasing fasting glucose levels at one, four, and/or 12 months post-transplant were significantly related to CV events. Furthermore, these relationships were independent of other CV risk factors, including: older age, CV events pretransplant, male gender, dyslipidemia, and transplant year. Fasting glucose levels >100 mg/dL were associated with higher incidence of post-transplant cardiac (P= 0.001) and peripheral vascular disease events (P= 0.003)., Conclusion: The incidence of post-transplant hyperglycemia and its CV impact have been underestimated. Pretransplant characteristics and, particularly, the glycemia during the first month post-transplant identified patients at risk of PTDM. Increasing glucose levels greater than 100 mg/dL, any time after the first month post-transplant, are associated with increasing CV risk. We postulate that aggressive detection and treatment of post-transplant hyperglycemia may significantly reduce CV morbidity and mortality after kidney transplantation.

Background: In patients with interrupted aortic arch echocardiography provides detailed information about the anatomy of the aortic arch and the associated cardiac anomalies. Only a few reports have evaluated the reliability of this non-invasive diagnostic procedure by correlation with angiographic and surgical findings., Methods: From 1988 through 1993, 45 infants with interrupted arch underwent surgical repair (mean age 13.02 days). Of the patients, 33 had interruption of the arch between the left common carotid and subclavian arteries; 25 patients had a ventricular septal defect, and the remaining 20 had coexisting complex congenital heart defects. Preoperative diagnosis was made exclusively by echocardiography in 25 of the patients. Accuracy of echocardiographic diagnosis was evaluated retrospectively by comparing preoperative studies with angiography and surgical reports. We then investigated whether the morphologic features of the interrupted arch might influence surgical procedure or outcome., Results: Intracardiac anatomy was accurately diagnosed by echocardiography in all cases; in 2 patients angiography provided additional information concerning the morphology of the aortic arch. Operative notes described differences in morphology of the arch in 7 patients, but these did not influence the surgical procedure. Direct anastomosis of the interrupted segments was possible in 38 patients, and 36 patients underwent primary intracardiac repair. Echocardiographic measurements revealed that the diameter of the ascending aorta was related to the number of vessels originating from the proximal aortic arch. The distance between the interrupted segments was significantly different according to the site of interruption, but not between cases with an isolated ventricular septal defect versus those with complex heart disease. It did not influence the method of arch repair, nor was it related to recurrent or residual obstruction., Conclusion: Preoperative echocardiography offers accurate and complete diagnosis in the critically ill neonate with interrupted aortic arch and associated intracardiac abnormalities.

Background: Although most neonates with d-transposition of the great arteries (TGA) have an uncomplicated preoperative course, some with a restrictive foramen ovale (FO), ductus arteriosus (DA) constriction, or pulmonary hypertension may be severely hypoxemic and even die shortly after birth. Our goal was to determine whether prenatal echocardiography can identify these high-risk fetuses with TGA., Methods and Results: We reviewed the prenatal and postnatal echocardiograms and outcomes of 16 fetuses with TGA/intact ventricular septum or small ventricular septal defect. Of the 16 fetuses, 6 prenatally had an abnormal FO (fixed position, flat, and/or redundant septum primum). Five of the 6 had restrictive FO at birth. Five fetuses had DA narrowing at the pulmonary artery end in utero, and 6 had a small DA (diameter z score of <-2.0). Of 4 fetuses with the most diminutive DA, 2 also had an abnormal appearance of the FO, and both died immediately after birth. One other fetus had persistent pulmonary hypertension. Eight fetuses had abnormal Doppler flow pattern in the DA (continuous high-velocity flow, n=1; retrograde diastolic flow, n=7)., Conclusions: Abnormal features of the FO, DA, or both are present in fetuses with TGA at high risk for postnatal hypoxemia. These features may result from the abnormal intrauterine hemodynamics in TGA. A combination of restrictive FO and DA constriction in TGA may be associated with early neonatal death.

We describe two families with Adams-Oliver syndrome (AOS), an autosomal dominant malformation syndrome (MIM No. 10030), in which cardiovascular malformations (CVMs) have been reported previously. In the first family, twin boys and their mother had the typical digital and scalp defects of AOS with various obstructive CVMs of the left heart (bicuspid aortic valve, Shone's complex). At least three other relatives not examined personally are reported to have related CVMs (aortic valve stenosis, hypoplastic left heart syndrome). In the second family, a girl had typical AOS digital and scalp defects and a bicuspid aortic valve. At least three other relatives are reported to be mildly affected. Tetralogy of Fallot had been previously reported as the most common CVM in AOS [Zapata HH, Sletten LJ, Pierport MEM (1995). J Med Genet 47:80-84.]. However, with the addition of these new patients and two other literature reports, we emphasize that approximately 20% have a CVM, frequently obstructive lesions of the left heart. Cardiology consultation should be offered to most patients with AOS.

A newborn female infant was found to have a unique and previously unreported group of anomalies: (1) mitral and aortic atresia with a highly obstructive atrial septum; (2) hypoplasia of the right lung with a crossover segment involving the right lower lobe; (3) normally connected pulmonary veins, two from the left lung and one from the right; and (4) a large anomalous branch of the right pulmonary vein of scimitar configuration that anastomosed with the normally connected right pulmonary vein and with the inferior vena cava (IVC). The scimitar vein appeared obstructed at its junction with the right pulmonary vein and at its junction with the inferior vena cava within the hepatic parenchyma. To our knowledge, this is the first report of a scimitar-like vein coexisting with mitral and aortic atresia and connecting both with the right pulmonary vein and with the inferior vena cava. The highly obstructed left atrium was partially decompressed by retrograde blood flow via the normally connected right pulmonary vein to the anomalous scimitar venous pathway and thence to the inferior vena cava via a pulmonary-to-IVC collateral vein.

To investigate the accuracy of immediate postbypass transesophageal echocardiography in the assessment of residual cardiac defects, we compared intraoperative transesophageal echocardiograms with intra/postoperative data in 86 patients, aged 4 days to 30.7 years (median = 1.4 years), at risk for a total of 174 postoperative lesions: right (n = 55) or left (n = 26) ventricular outflow tract obstruction, ventricular septal defect (n = 65), aortic (n = 12) or mitral regurgitation (n = 8), or mitral stenosis (n = 8). Accuracy of intraoperative transesophageal echocardiography was evaluated based on comparison with (1) immediate post-bypass left (n = 4) or right (n = 9) ventricular outflow tract pressure gradients by pullback in the operating room, (2) direct surgical inspection of residual ventricular septal defects (n = 3), (3) pulmonary artery oxygen saturation (n = 49), (4) right ventricular outflow tract pullback gradient (n = 24), and (5) transthoracic echocardiogram (n = 51) performed within 40 days of surgery. The results indicate that intraoperative transesophageal echocardiography agreed with intra/postoperative data in 87% of patients at risk for right ventricular outflow tract obstruction, 96% at risk for left ventricular outflow tract obstruction, 97% at risk for ventricular septal defect, and 100% at risk for aortic regurgitation, mitral regurgitation, or mitral stenosis. Significant residual lesions led to immediate surgical revision in 11 cases: 3 ventricular septal defects, 6 right and 2 left ventricular outflow tract obstructions. Of these, intraoperative transesophageal echocardiography confirmed and quantified suspected residual lesions in 7 and identified unsuspected lesions in 4 cases. Immediate postbypass transesophageal echocardiography proved reliable for assessing residual ventricular septal defect, mitral stenosis, and mitral or aortic regurgitation. Although accurate for assessment of the left and right ventricular outflow tracts in most patients, transesophageal echocardiography may not reliably reflect the severity of obstruction in all cases.

Background: Cardiovascular stability is an important prerequisite for any new volatile anesthetic. We compared echocardiographically derived indices of myocardial contractility during inhalation induction with sevoflurane and halothane in children., Methods: Twenty children were randomized to receive either halothane or sevoflurane for inhalation induction of anesthesia. No preoperative medications were given. Myocardial contractility was evaluated at baseline and at sevoflurane and halothane end-tidal concentrations of 1.0 minimum alveolar concentration (MAC) and 1.5 MAC., Results: There were no differences between groups in patient age, sex, physical status, weight, or height. Equilibration times and MAC multiples of sevoflurane and halothane were comparable. Vital signs remained stable throughout the study. Left ventricular end-systolic meridional wall stress increased with halothane but remained unchanged with sevoflurane. Systemic vascular resistance decreased from baseline to 1 MAC and 1.5 MAC with sevoflurane. Halothane depressed contractility as assessed by the stress-velocity index and stress-shortening index, whereas contractility remained within normal limits with sevoflurane. Total minute stress and normalized total mechanical energy expenditure, measures of myocardial oxygen consumption, did not change with either agent., Conclusions: Myocardial contractility was decreased less during inhalation induction of anesthesia with sevoflurane compared with halothane in children. Although the induction of anesthesia with sevoflurane or halothane was equally well tolerated, the preservation of myocardial contractility with sevoflurane makes it an attractive alternative for inducing anesthesia in children.

Objectives: This study sought to determine risks and outcome of pregnancy and delivery after the modified Fontan operation., Background: Increasingly, female Fontan patients reaching child-bearing years are interested in having children. To date, the number of reported pregnancies is small, and pregnancy has therefore been discouraged., Methods: One hundred ten of 126 female patients from the Fontan registries of the Mayo Clinic and University of California Los Angeles Medical Center responded to a mailed questionnaire. An additional six patients with a reported pregnancy from other centers were identified and reviewed to assess pregnancy outcomes., Results: Among the participating centers, a total of 33 pregnancies after Fontan operation for various types of univentricular heart disease were reported. There were 15 (45%) live births from 14 mothers, with 13 spontaneous abortions and 5 elective terminations. In the 14 women with live births, the median number of years between operation and pregnancy was 4 (range 2 to 14). Reported prepregnancy problems in these gravidas included atrial flutter in one patient and ventricular dysfunction, aortic regurgitation and atrioventricular valve regurgitation in another. One patient developed supraventricular tachycardia during pregnancy and had conversion to sinus rhythm. No maternal cardiac complications were reported during labor, delivery or the immediate puerperium. There were six female and nine male infants (mean gestational age 36.5 weeks; median weight 2,344 g). One infant had an atrial septal defect. At follow-up, mothers and infants were alive and well., Conclusions: Pregnancy after the Fontan operation appears to have been well tolerated in 13 to 14 gravidas. There does appear to be an increased risk of miscarriage. The tendency to routinely discourage pregnancy may need to be reconsidered.

We reviewed pre-closure echocardiograms on all patients undergoing transcatheter atrial septal defect (ASD) closure with the Bard double-umbrella occluder device aided by simultaneous transesophageal echocardiography to determine precatheterization predictors of outcome. Transesophageal echocardiograms were performed on 28 of 132 patients (22%) undergoing device closure (age = 3-72 years, mean = 14 years; weight = 15-68 kg, mean = 35 kg). Three devices were removed because of unstable position. Of the remaining 25 patients, 21 had effective closure (residual flow diameter < or = 3 mm) and 18 had favorable arm position (device arm on proper side of the septum and not in contact with an atrioventricular valve leaflet). Only ASD size predicted effective closure. All patients with a maximum defect size of < 13 mm had effective closure. Among the 17 patients with defects > or = 13 mm, 10 had effective closure, 4 had significant residual flow, and 3 had devices removed for unstable position. Atrial dimensions and rim size did not predict effective closure. There were no pre-closure predictors of favorable arm position which was associated only with the size of the device implanted.

Recent development of prototype pediatric biplane transducers has extended the use of biplane TEE imaging to the neonate. One such TEE probe with 64 imaging elements in each pallet was used perioperatively in 46 infants and children (weight 2.9 to 32 kg) undergoing surgery for complex congenital heart disease. The success rate for passing the transducer, complications of the procedure, and the number of cases in which the vertical plane provided information that was not available from the horizontal plane were determined. Probe insertion was successful in all patients. Imaging was discontinued in one neonate because of possible airway compression by the probe. Image quality was excellent in the other 45 patients. The vertical plane added information over that obtained from the horizontal plane in 58 (44%) of the 132 anomalies identified. The addition of the vertical plane was especially useful in imaging abnormalities of the ventricular outflow tracts.

Objectives: The reliability of two-dimensional echocardiography for determining the proximal coronary artery anatomy in d-loop transposition of the great arteries was investigated in 406 infants who underwent surgical repair at one institution., Background: The origin and proximal course of the main coronary arteries can affect the surgical results of the arterial switch operation. Preoperative determination of the coronary artery anatomy appears to be advantageous for the surgeon., Methods: All infants with d-loop transposition who underwent a two-dimensional echocardiogram and primary surgical repair at our institution between 1987 and 1992 were identified, and the echocardiographic, operative and, when available, autopsy reports were reviewed for coronary artery anatomy, presence of a ventricular septal defect and the spatial relation between the arterial roots. The two-dimensional echocardiographic findings were compared with surgical or autopsy findings. The relation between proximal coronary artery anatomy and 1) a ventricular septal defect, and 2) the spatial orientation of the arterial roots was investigated. Twenty-seven infants diagnosed with an intramural coronary artery were not included because they are the subjects of another report., Results: Excluding intramural coronary artery patterns, 10 different types of coronary artery anatomy were seen in these 406 patients. The coronary arteries were imaged adequately in 387 (95%) of the 406 patients. The coronary artery anatomy was determined correctly by two-dimensional echocardiography in 369 (95.4%) of the 387 patients, with 18 errors in diagnosis. During the most recent 2.5 years, 193 (98.5%) of 196 patients were diagnosed correctly, with three diagnostic errors. Patients with a ventricular septal defect or side-by-side great arteries are more likely to have an unusual coronary pattern., Conclusions: Echocardiography appears to be highly reliable for determining proximal coronary artery anatomy in d-loop transposition of the great arteries. An unusual coronary artery pattern is more likely in patients with side-by-side great arteries or posterior aorta or a ventricular septal defect, or both.

Objectives: This report describes transesophageal echocardiographic guidance of transcatheter closure of ventricular septal defects and its value as an adjunct to fluoroscopy and angiography in this procedure., Background: Experience with transcatheter closure of ventricular septal defects has identified a diverse group of patients in whom it may be the procedure of choice. Although facilitating other interventional procedures, such as transcatheter closure of atrial septal defects, the value of transesophageal echocardiographic guidance for transcatheter ventricular septal defect closure has not been documented., Methods: All patients who underwent ventricular septal defect closure with transesophageal echocardiographic guidance before November 1992 were included. Angiograms and echocardiograms were reviewed to evaluate device position and relation to valve tissue during placement and to assess residual flow after device implantation. The ability of transesophageal echocardiography to assess these variables was compared with fluoroscopy and angiography., Results: Transesophageal echocardiographic guidance was used in 31 of the 83 catheterizations involving transcatheter ventricular septal defect closure performed between February 1990 and November 1992. Under transesophageal echocardiographic guidance, 45 devices were implanted: 23 in muscular ventricular septal defects, 17 in residual postoperative patch margin defects and 5 in other ventricular septal defects. Transesophageal echocardiographic guidance enhanced assessment of device position and proximity to valve structures and markedly improved assessment of residual flow. Assessment of residual flow with transesophageal echocardiography eliminated the need for multiple angiograms in some patients. Combining transesophageal echocardiography with fluoroscopy and angiography provided the most information., Conclusions: Transesophageal echocardiography facilitates transcatheter closure of ventricular septal defects by improving assessment of device position and effectiveness of closure. It is indicated when device placement is likely to be difficult or may interfere with valve structures or when multiple interventional procedures are anticipated.

The purpose of this study was to compare Doppler color flow mapping with angiography and surgical observation for detection of multiple ventricular septal defects (VSDs). Only patients with elevated pulmonary ventricular pressure were included. Among 137 patients with VSDs, 38 multiple defects were identified in 25 patients echocardiographically, 34 multiple defects in 24 patients angiographically, and 21 multiple defects in 17 patients surgically. Using surgical observation as the reference standard, the sensitivity of echocardiography for identifying patients with multiple VSDs was 17 of 17 (100%) and for angiography 15 of 17 (88%). The sensitivity of echocardiography for identifying all multiple VSDs seen at operation was 19 of 21 (90%) and of angiography was also 19 of 21 (90%). In many patients, use of both techniques may no longer be necessary.

The clamshell double umbrella (Bard Clamshell Septal Umbrella, USCI Division, C. R. Bard, Billerica, MA) was developed to allow closure of septal defects, both atrial and ventricular. The device and delivery system and the techniques for implanting the device in atrial and ventricular defects are described in detail. Although fractures of the arms supporting the umbrellas in some patients have lead to modification of the device, the early experience in clinical trails are encouraging.

Background: Anomalous origin of the left coronary artery from the pulmonary trunk is difficult to diagnose reliably by two-dimensional echocardiography. Therefore, Doppler color flow mapping was tested in 29 patients with dilated cardiomyopathy or anomalous left coronary artery, or both., Methods and Results: All patients with anomalous left coronary artery (10 patients) or dilated cardiomyopathy (27 patients) (excluding those with other known causes for cardiomyopathy) examined between January 1988 and May 1991 were identified. The direction of flow in the three main segments of the left coronary system was determined by Doppler color flow mapping. In all 10 patients with anomalous left coronary artery, flow mapping demonstrated an abnormal jet from the left coronary artery into the pulmonary trunk and retrograde flow in at least two segments of the left coronary system. The diagnosis was confirmed in all 10 patients at operation. Doppler color flow mapping, performed in 19 of the 27 patients with dilated cardiomyopathy, demonstrated anterograde flow in at least one segment of the left coronary system in 16 of the 19 patients; flow direction was not determined in the other 3 patients. Coronary artery anatomy was confirmed by aortic root or left ventricular angiography in 14 patients and at autopsy in 1 patient and was not directly confirmed in 4 patients. Left ventricular function spontaneously improved to normal in three of the latter four patients, a clinical course not consistent with anomalous left coronary artery. The left coronary artery appeared to arise from the aortic root by two-dimensional echocardiographic imaging alone in all patients with dilated cardiomyopathy and in 5 of 10 patients with anomalous left coronary artery (50% false negative diagnoses)., Conclusions: Detection of an abnormal jet into the pulmonary trunk and retrograde flow in the left coronary system by Doppler color flow mapping is reliable for diagnosing anomalous left coronary artery whereas two-dimensional echocardiographic imaging alone is often inconclusive or misleading. Determining flow direction in the left coronary system in patients with dilated cardiomyopathy is useful for excluding anomalous left coronary artery but is technically more difficult to document in this condition than in anomalous left coronary artery.

Bulboventricular foramen obstruction may complicate the management of patients with single left ventricle. Bulboventricular foramen size was measured in 28 neonates and infants greater than 5 months old and followed up for 2 to 5 years in those patients whose only systemic outflow was through the foramen. The bulboventricular foramen was measured in two planes by two-dimensional echocardiography, its area calculated and indexed to body surface area. One patient died before surgical treatment. The mean initial bulboventricular foramen area index was 0.94 cm2/m2 in 12 patients (Group A) in whom the foramen was bypassed as the first procedure in early infancy. The remaining 15 patients underwent other palliative operations but the bulboventricular foramen continued to serve as the systemic outflow tract. There was one surgical death. Six (Group B) of the 14 survivors developed bulboventricular foramen obstruction during follow-up (mean initial bulboventricular foramen area index 1.75 cm2/m2). The remaining eight patients (Group C) did not develop obstruction during follow-up and had an initial bulboventricular foramen larger than that in the other two groups (mean initial bulboventricular foramen area index 3.95 cm2/m2). All patients with an initial bulboventricular foramen area index less than 2 cm2/m2 who did not undergo early bulboventricular foramen bypass developed late obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

The records of 23 infants who underwent surgical repair of isolated totally anomalous pulmonary venous connection were reviewed to assess the accuracy of pre- and postoperative echocardiographic diagnoses. Preoperative echocardiographic diagnoses were accurate in 22 of 23 patients, including the sites of connection of the individual pulmonary veins. Cardiac catheterization in 13 patients confirmed the echocardiographic findings. Analysis of multiple pre- and postoperative variables revealed no statistically significant difference between the infants with and without catheterization, although there was a tendency toward a higher mortality rate in the catheterized group. Postoperative echocardiographic examination revealed obstruction to pulmonary venous return in 7 of 19 patients. Catheterization confirmed the echocardiographic findings, localizing the obstruction in one patient. The size of the venoatrial anastomosis was measured on postoperative echocardiograms performed on 14 patients. The cross-sectional area of the anastomosis was less than 0.3 cm2/m2 of body surface area in the four patients with obstruction of the anastomosis, and greater than 0.95 cm2/m2 in all long-term survivors examined. Two-dimensional echocardiography with pulsed Doppler examination and Doppler color flow mapping is an excellent means of diagnosing totally anomalous pulmonary venous connection. The connections of the individual pulmonary veins can be identified in nearly all cases. Surgical repair can usually be undertaken on the basis of echocardiographic diagnosis alone. Echocardiography also provides an extremely accurate method of evaluating surgical repair and of identifying and localizing postoperative obstruction to pulmonary venous return.

Echocardiography has been used during interventional cardiac catheterization for guidance of the procedure and assessment of results. However, limited echocardiographic windows and logistical difficulties make conventional echocardiography during interventional catheterization impractical and of limited value. Transesophageal echocardiography (TEE) with Doppler color flow mapping is more useful than conventional echocardiography for guidance of interventional catheterizations. Device closure of congenital atrial and ventricular septal defects (ASDs and VSDs) and of postoperative residual interatrial and interventricular communications, balloon valvuloplasty, and Brockenbrough atrial septal puncture with ASD creation have been performed under combined fluoroscopic and TEE guidance. Transesophageal echocardiography can be performed continuously throughout the procedure, allowing simultaneous fluoroscopic and echocardiographic assessment of catheter position. Localization of individual device arms during transcatheter device closure of ASDs and VSDs is easier and more accurate when TEE is used, resulting in a lower incidence of incorrect device positioning. Doppler color flow mapping is used to determine number, location, and size of defects, to detect residual shunts after device closure, and to assess valve insufficiency after balloon valvuloplasty and other procedures. Combined TEE and fluoroscopic guidance of interventional procedures, with echocardiographic assessment of results, reduces the amount of radiation and contrast used during the procedure, allowing performance of additional interventional procedures during the same catheterization. Transesophageal echocardiography is indicated during interventional procedures in which simultaneous Doppler color flow mapping and precise localization of catheter, balloon and/or device position will result in a higher success rate and decreased morbidity.

Lactoferrin is a metal binding protein, which is present in high concentrations in human tears. Little is known concerning the exact molecular shape of lactoferrin in tears. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting experiments showed that this protein is present in multiple forms in tear fluid. SDS-PAGE analysis of human tears under non reducing conditions and pretreatment of tears in sample buffer at room temperature revealed lactoferrin in a major form of 60 kD, a minor form of 64 kD and a third form of 52 kD. Pretreatment of tears at elevated temperatures prior to sample application resulted in the loss of this third form. Disruption of intrachain disulfide bridges prior to SDS-PAGE analysis resulted in a shift in the apparent molecular weight of lactoferrin to 78 kD and 83 kD for the major and minor form, respectively. Chromatography of human tears on ConA-Sepharose as well as enzymatic deglycosylation showed that the difference in molecular weight of the major and minor lactoferrin form was not due to a variation in the carbohydrate side chains. The presence of the minor form could also not be ascribed to iron saturation. Instead we found that addition of iron ions to human tears resulted in a shift of tear lactoferrin to a lower molecular weight species of about 52 kD, coinciding with the third lactoferrin form mentioned above and a small protein band of approximately 57 kD, representing the iron saturated minor lactoferrin form. Similar findings were observed using purified milk lactoferrin. Increasing the temperature prior to sample application or disruption of disulfide bridges dissociated the iron-lactoferrin complex.(ABSTRACT TRUNCATED AT 250 WORDS)

At a corrected age of 3 months, 80 low birth-weight infants were assigned to normal or at-risk groups on the basis of a neurodevelopmental assessment scale. Both groups were further divided into intervention and non-intervention sub-groups (20 infants in each). Intervention consisted of monthly hospital-based neurodevelopmental therapy in addition to a home exercise programme. Infants were re-assessed by a physiotherapist at 6, 9, and 12 months, and were tested at 12 months by an independent psychologist blinded for infant group. Mean birthweight and gestational age were similar for normal and at-risk groups. At-risk infants had higher mean neurodevelopmental scores throughout the study period and lower 1-year development quotients (DQ) than normals. In neither normal nor at-risk groups did neurodevelopmental therapy alter the pattern of development or the outcome.