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CD39 (ENTPD1) is a key enzyme responsible for degradation of extracellular ATP and is upregulated in the tumor microenvironment (TME). Extracellular ATP accumulates in the TME from tissue damage and immunogenic cell death, potentially initiating proinflammatory responses that are reduced by the enzymatic activity of CD39. Degradation of ATP by CD39 and other ectonucleotidases (e.g., CD73) results in extracellular adenosine accumulation, constituting an important mechanism for tumor immune escape, angiogenesis induction, and metastasis. Thus, inhibiting CD39 enzymatic activity can inhibit tumor growth by converting a suppressive TME to a proinflammatory environment. SRF617 is an investigational, anti-CD39, fully human IgG4 Ab that binds to human CD39 with nanomolar affinity and potently inhibits its ATPase activity. In vitro functional assays using primary human immune cells demonstrate that inhibiting CD39 enhances T-cell proliferation, dendritic cell maturation/activation, and release of IL-1β and IL-18 from macrophages. In vivo, SRF617 has significant single-agent antitumor activity in human cell line–derived xenograft models that express CD39. Pharmacodynamic studies demonstrate that target engagement of CD39 by SRF617 in the TME inhibits ATPase activity, inducing proinflammatory mechanistic changes in tumor-infiltrating leukocytes. Syngeneic tumor studies using human CD39 knock-in mice show that SRF617 can modulate CD39 levels on immune cells in vivo and can penetrate the TME of an orthotopic tumor, leading to increased CD8+ T-cell infiltration. Targeting CD39 is an attractive approach for treating cancer, and, as such, the properties of SRF617 make it an excellent drug development candidate.

Models predicting disease transmission are vital tools for long-term planning of malaria reduction efforts, particularly for mitigating impacts of climate change. We compared temperature-dependent malaria transmission models when mosquito life-history traits were estimated from a truncated portion of the lifespan (a common practice) versus traits measured across the full lifespan. We conducted an experiment on adult female Anopheles stephensi, the Asian urban malaria mosquito, to generate daily per capita values for mortality, egg production and biting rate at six constant temperatures. Both temperature and age significantly affected trait values. Further, we found quantitative and qualitative differences between temperature–trait relationships estimated from truncated data versus observed lifetime values. Incorporating these temperature–trait relationships into an expression governing the thermal suitability of transmission, relative R0(T), resulted in minor differences in the breadth of suitable temperatures for Plasmodium falciparum transmission between the two models constructed from only An. stephensi trait data. However, we found a substantial increase in thermal niche breadth compared with a previously published model consisting of trait data from multiple Anopheles mosquito species. Overall, this work highlights the importance of considering how mosquito trait values vary with mosquito age and mosquito species when generating temperature-based suitability predictions of transmission.

Methods, Results, Discussion

Monte Carlo simulations using MCNP6.1 were performed to study the effect of neutron activation in Ar/CO

An interspecies deer hybrid resource population developed from a cross of Pere David's and red deer was used to detect QTL that account for species differences. A genome scan, coupled with composite interval mapping, was conducted to search for QTL controlling body measurements at pre-pubescent age (6 months of age) and puberty (15 months of age) in this interspecies hybrid. Five linkage groups that harbour QTL affecting morphology were identified. A joint-traits analysis was used to search for putative pleiotropic QTL on four of these linkage groups, and three were significantly associated with pleiotropic QTL for nose width and foot length (metacarpal and phalanges), which collectively accounted for 29-58% of the phenotypic difference between the two deer species. This study suggests that a few loci with large pleiotropic effects may be responsible for species-specific differences in growth and structure-related traits.

The effect on nisin production of increasing nisin immunity/resistance genes in Lactococcus lactis subsp. lactis MG1363 was investigated. The 60-kb nisin immunity/resistance plasmid pND300, which was isolated from a non-nisin-producing strain, encodes five genes involved in nisin immunity/resistance, which are very similar to those of the immunity/resistance system encoded by the nisin-production transposon. The introduction of pND300 into MG1363(TnNip) resulted in the construct being able to produce significantly more nisin than the parent MG1363(TnNip). The introduction of pND314, which contains the nisin immunity/resistance genes subcloned into pSA3, into MG1363(TnNip) allowed the strain to grow more rapidly than the parent MG1363(TnNip) with a concomitant increase in the rate of nisin production. This work illustrates that introduction of pND300 and a derivative containing the nisin immunity/resistance system of pND300 into MG1363 (TnNip) can result in significant alterations to the kinetics of nisin production. These observations indicate approaches that may be used successfully to improve the economics of nisin production.

The occurrence and spatial distribution of top kill 1 year following a jack pine budworm (Choristoneura pinus pinus Freeman) outbreak were examined for possible associations with forest stand characteristics derived from resource inventory maps. Associations were computed between top-kill severity and jack pine (Pinus banksiana Lamb.) maturity, stand height, crown closure, and site quality. Three different measures of association with data from a geographic information system (GIS) (Cramer's V, Spearman's nonparametric rank correlation, and Minnick's coefficient of areal determination) were used to assess the strength of these associations. There were no statistical differences among average top-kill lengths, which averaged 2 m, among the light, moderate, and severe top-kill categories. The proportion of trees that experienced top kill ranged from 55% in the light to 61% in the severe top-kill classes. Site quality and stand maturity were more highly associated with top kill than stand height and crown closure. Jack pine areas that sustained moderate and severe top kill were those on poor sites that were overmature (> 85 years), 15-20 m tall with 30-55% crown closure. The GIS approach can be a useful tool for identifying vulnerable stands, and increasingly so as forest inventory classification systems become more detailed.

The kinetics of nisin production was studied in batch cultures using a construct of Lactococcus lactis subsp. lactis C2SmPrt-, containing a transposon (TnNip) that encodes nisin production. The introduction of TnNip into C2SmPrt- significantly lowered the specific growth rate and the maximum A620 reached was reduced from 15.2 to 11.0. The effect of nisin concentration and nutrient depletion on nisin production of the construct, C2SmPrt-(TnNip), was examined. Nisin production was found to be inhibited by high concentrations of nisin, when grown in excess nutrient, even though growth of the culture continued because nutrient limitation was not operating. However, in low nutrient concentrations nisin production was limited by nutrient depletion. The specific growth rate of C2SmPrt-(TnNip) was altered, by using different nutrient concentrations and different sugars, in order to examine the relationship between nisin production and growth. Nisin production was shown to be growth-associated for most of growth, but near the end of growth, when the specific growth rate was 0.05 h-1 or less, the production ceased.

Kinetics of nisin production have been investigated in terms of endogenous features of the producer organism, Lactococcus lactis. Nisin-producing transposons (Tn Nip) were transferred to different hosts by conjugation. Constructs were cultivated in batch cultures and nisin produced was measured. The proteinase function of C2Prt (Tn Nip)-1 was eliminated by plasmid curing, resulting in the construct C2Prt - (Tn Nip)-1. C2Prt - (Tn Nip)-1 produced nisin to a higher concentration compared to C2Prt (Tn Nip)-1 and was able to maintain the maximum concentration till the end of cultivation. The final concentration of nisin produced was host-specific, because when different constructs carrying the same Tn Nip were cultivated they produced nisin to different concentrations. However, when the same host carried Tn Nip transposons derived from different donors the concentration of nisin produced was similar, suggesting that the two Tn Nip transposons may be similar.

Nous avons effectue une etude en laboratoire pour mesurer l'efficacite d'assimilation du chlorure de methyl[ 203 Hg]mercure (CH 3 203 HgCl) present dans la nourriture des ecrevisses (Orconectes virilis) et le taux subsequent de depuration du CH 3 203 HgCl assimile. L'efficacite moyenne d'assimilation du CH 3 203 HgCl chez les tetards etait de 96%. Chez la majorite des 50 ecrevisses de l'experience (trois classes de taille de mâles et de femelles designees comme petite, moyenne et grande), on n'a observe sur la periode d'etude de 166 jours aucune disparition significative du CH 3 203 HgCl assimile. Quand une disparition significative du CH 3 203 HgCl etait detectee, les demi-vies observees tombaient generalement entre 1000 et 2000 jours (3-5 ans). La forte efficience d'assimilation et le faible taux de depuration permettent de penser que les ecrevisses peuvent bioamplifier le CH 3 Hg a partir de leur nourriture.

Studies on emergence of insect communities conducted in Mud Creek and Costello Creek in Algonquin Park, Ontario, Canada, over a period of 50 yr were analyzed to assess the changes that have occurred in blackfly populations in streams receiving long-term anthropogenic acidification. The headwaters of Mud Creek are currently experiencing pH depressions to 5.1–4.9 during snowmelt whereas pH depressions downstream in Mud Creek and throughout Costello Creek are less severe (to pH 5.6–5.8) compared with summer and autumn values of about 6.4. Since the time of the earliest collections, the total number of blackflies emerging has increased at the most severely acidified sites at the headwaters of Mud Creek, while emergence remains unchanged at all the less acidified sites. Large fluctuations from year to year in the emergence densities of many individual species were observed at all sites, making it difficult to determine which species may increase or decrease concurrent with elevated acidity.

An investigation to determine the responses of immature blackflies to experimental pulses of acidity simulating snowmelt episodes was conducted. Five species of mature blackfly larvae were subjected to 3- or 4-d experimental pH depressions to approximately 4.0 or 3.5 in stream channels. Differences among species in response to acidity were observed. All species except Simulium vittatum and possibly S. venustum were able to tolerate pH depressions to approximately 4.0, while only Cnephia dacotensis and possibly S. decorum were able to tolerate pH depressions to approximately 3.5. The survival of the larvae (only late instars were tested) was significantly affected by the acidity, while pupal survival generally was not. The rate of pupation, however, was decreased in the acidified channels, resulting in decreased emergence there also. More abnormally formed pupae developed in the acidified channels, suggesting that pupation following snowmelt ensures survival of these species.

The operational feasibility of using large-scale aerial photographs to quantify coniferous forest stocking and regeneration density, was assessed over 6 cutovers with a 1,700 ha total area. The project involved two stages: one to pre-stratify cutover stocking levels using 1:10,000 general-coverage, colour photos; and the second to sample intensively, stocking and density using 1:500 large-scale photos. The accuracy, cost and practical problems in using large-scale sampling photos for regeneration assessment were determined. Accuracy assessment included detectability of young trees, species interpretation, and reliability of stocking and density measurements. Stocking estimates were on average, only five percent lower than field survey results but could be calibrated using regression techniques. Large differences between field survey and photo estimates of density in stems/ha suggested such counts should not be made from large-scale photos. Density count differences were attributable to seedlings occurring in dense patches or clumps where field counts were also difficult. If survey objectives and methods are carefully planned, large-scale photos can be a suitable tool for assessing and monitoring the stocking and survival rates of coniferous forest regeneration. Key words: Forest regeneration appraisal, silviculture, inventory, sampling, large-scale photography.

Bacteraemia is common following some forms of gastrointestinal endoscopic therapy, such as dilatation or injection sclerotherapy, and can occur with diagnostic endoscopy alone. Fortunately complications resulting from dissemination of endogenous bacteria are uncommon, and infective endocarditis is an extremely rare complication. Furthermore, for most diagnostic and therapeutic procedures there is scant evidence that antibiotic prophylaxis can reduce the incidence of infective complications. The area that has attracted the most controversy in recent years has been the use of antibiotics to prevent infective endocarditis. The recommendations by the American Heart Association (AHA)1 have traditionally guided the advice of the national bodies representing endoscopic practice,2 3 including the British Society of Gastroenterology (BSG).4 The traditional guidance has been that patients at high risk of endocarditis, such as those with a prosthetic (ie, tissue or mechanical) valve and/or a past history of endocarditis should receive antibiotics for all endoscopic procedures. More recently the European Society of Cardiology recommended antibiotic prophylaxis to cover therapeutic endoscopy in patients with acquired valvular heart disease,5 and the British Cardiovascular Society went even further, advising antibiotic prophylaxis for patients at moderate risk of endocarditis undergoing any endoscopic procedure.6 The Endoscopy Committee of the BSG recognised the need for consensus on this issue, and convened a Working Party in the spring of 2006. The membership, comprised doctors with a special interest in gastroenterology, gastroenterologists, cardiologists and microbiologists. The gastroenterologists and microbiologists from this Working Party also took the opportunity to review the evidence underpinning the use of antibiotic prophylaxis in other areas of endoscopic practice, in particular endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous endoscopic gastrostomy (PEG). In view of new guidance from the AHA, and from the National Institute for Health and Clinical Excellence (NICE), the Working Party reconvened in 2008 to reconsider, in …

An interspecies deer hybrid resource population developed from a cross of Père David's and red deer was used to detect QTL that account for species differences. A genome scan, coupled with composite interval mapping, was conducted to search for QTL controlling body measurements at pre-pubescent age (6 months of age) and puberty (15 months of age) in this interspecies hybrid. Five linkage groups that harbour QTL affecting morphology were identified. A joint-traits analysis was used to search for putative pleiotropic QTL on four of these linkage groups, and three were significantly associated with pleiotropic QTL for nose width and foot length (metacarpal and phalanges), which collectively accounted for 29-58% of the phenotypic difference between the two deer species. This study suggests that a few loci with large pleiotropic effects may be responsible for species-specific differences in growth and structure-related traits.

This report describes a technique for removal of a segmental broken intramedullary femoral rod. Using a closed, stacked wire technique, removal of the broken hardware can be accomplished in a relatively easy and expeditious manner.

Satellite-based mapping can provide a timely and efficient means of identifying burned vegetation at continental scales for estimating greenhouse gas emissions and its effects on the terrestrial carbon budget. In this study, we used a sample of 55 Landsat Thematic Mapper (TM) scenes distributed across Canada to validate and calibrate 1998 and 1999 national-level burned areas maps produced using coarse resolution (~ 1-km) SPOT VEGETATION and NOAA AVHRR imagery. Commission and omissions errors, based on fire events > 200 ha, were found to be small in the coarse resolution maps (4% and 1%, respectively). However, the coarse resolution burned area estimates were 72 percent larger than the crown fire burned area mapped at 30 m using Landsat TM (11,039 vs. 6,403 ha average area). This bias was attributed to spatial aggregation effects in which the coarse resolution product included the tree crown fire, partial burn, and unburned fractions of a pixel. A regression calibration model (R2=0.95, p< 0.0005, RMS=3,015 ha, n=155) based on a VGT/TM double sampling approach was derived to correct for the aggregation bias and to provide Canada-wide estimates of crown fire burned area.

Several theories have suggested that age-related declines in cognitive processing are due to a pervasive unitary mechanism, such as a decline in processing speed. Structural equation model tests have shown some support for such common factor explanations. These results, however, may not be as conclusive as previously claimed. A further analysis of 4 cross-sectional data sets described in Salthouse, Hambrick, and McGuthry (1998) and Salthouse and Czaja (2000) found that although the best fitting model included a common factor in 3 of the data sets, additional direct age paths were significant, indicating the presence of specific age effects. For the remaining data set, a factor-specific model fit at least as well as the best fitting common factor model. Three simulated data sets with known structure were then tested with a sequence of structural equation models. Common factor models could not always be falsified--even when they were false. In contrast, factor-specific models were more easily falsified when the true model included a unitary common factor. These results suggest that it is premature to conclude that all age-related cognitive declines are due to a single mechanism. Common factor models may be particularly difficult to falsify with current analytic procedures.

Primary cultures of bovine ZF cells were incubated for 1 h or 6h with the agonists 8-bromo-cyclic AMP (8-Br-cAMP) an activator of protein kinase A (PKA), the phorbol ester phorbol 12-myristate 13-acetate (PMA) a protein kinase C (PKC) activator, the Ca2+ ionophore, A23187, or the L-type Ca2+ channel agonist Bay K8644. Both cortisol secretion (determined by radioimmunoassay of cell medium) and cellular StAR protein levels (quantified by western blotting) were significantly increased at 6h, by all agonists. However, while all agonists stimulated cortisol secretion at 1h, StAR protein levels remained unchanged by these treatments. We conclude that in bovine ZF cells, StAR protein synthesis can be regulated by mechanisms involving activation of PKA, PKC and Ca2+ influx. However, a net increase in cellular StAR protein does not appear to be essential for the initiation for the first stage of acute steroidogenesis.

Teneurin-2 is a member of a novel family of transmembrane proteins characterized to date in fish, birds, mammals, and Drosophila (e.g., the pair-rule gene product Ten-m). We have shown that teneurin-2 is expressed by neurons in the developing avian visual system in a pattern complementary to the expression of teneurin-1 and that recombinant teneurin-2 induces morphologic changes in neuronal cells in culture (Rubin et al., 1999). Here we have used cRNA probes to two newly identified splice variants and a teneurin-2-specific antibody to determine whether teneurin-2 is also expressed outside the nervous system. Both reverse transcriptase-polymerase chain reaction and in situ hybridization indicate that the three splice variants known so far are coexpressed at sites of pattern formation during development. Teneurin-2 mRNAs and protein are found in the developing limbs, somites, and craniofacial mesenchyme. In addition to expression of teneurin-2 by the apical ectodermal ridge, teneurin-2 transcripts also appear transiently at sites of tendon development. Teneurin-2 expression patterns were strikingly similar to those of fibroblast growth factor 8 (FGF8). In agreement with the overlapping expression pattern, FGF8-coated beads implanted into chicken limb buds induced the ectopic expression of teneurin-2 and soluble FGF8 induced teneurin-2 in limb explant cultures. Thus, teneurin-2 could act downstream of FGF8 during morphogenesis.

Using a monoclonal antibody raised against human platelet thrombospondin, we found anti-thrombospondin immunoreactivity in the extracellular matrix of avian embryos, coincident with the ventral pathways followed by trunk neural crest cells. To confirm that the antibody recognized thrombospondin-1 and to determine the tissue of origin of the thrombospondin matrix, a thrombospondin-1 cRNA probe was used for whole mount in situ hybridization. This probe revealed thrombospondin-1 mRNAs in the developing myotome before and during neural crest cell migration. The effect of thrombospondin-1 on neural crest cell migration, morphology, and adhesion was assayed in vitro. Quail trunk neural crest cells cultured on 4 microg/ml of thrombospondin-1 migrate at 1.14 +/- 0.54 microm/min, which is significantly greater than the rate of cell migration on tissue culture plastic. Using a shaker-based adhesion assay, a significantly greater number of neural crest cells remain attached to dishes coated with 4 microg/ml of thrombospondin-1 than to tissue culture plastic alone. The number of neural crest cells that remain attached to 4 microg/ml of thrombospondin-1 is similar to the number that remain attached to dishes coated with 10 microg/ml of fibronectin. These observations indicate that neural crest cells migrate through a thrombospondin-filled extracellular matrix, and that thrombospondin-1 promotes neural crest cell migration and adhesion. Thus, thrombospondin-1 is the first somite-derived extracellular matrix molecule with properties consistent with a role in the promotion of migration into the anterior somite, as opposed to the repulsion of neural crest cells from the posterior half of the somite.

An unusual case of dislocation of the midfoot through the calcaneocuboid and naviculocuneiform joints is presented. The prognosis is excellent for most midfoot dislocations, as long as they are recognized and treated early.

We conducted a retrospective review of Egyptian patients who underwent coronary artery bypass graft surgery at our institution between 1980 and 1995. We examined the prevalence of coronary artery disease risk factors and evaluated the early postoperative results. We then compared these results with the corresponding data in a subset of American patients who underwent coronary artery bypass grafting at our institution in 1993. There were 290 Egyptian patients: 275 men and 15 women. The mean age was 54.5 years (range, 30 to 70 years). Angina was present in 258 (89%) of the Egyptian patients; of these, 186 (72.1%) were in Canadian Cardiovascular Society class 3 or 4. Risk factor analysis revealed a high prevalence of hyperlipidemia (69.7%), cigarette-smoking (66.6%), family history of coronary artery disease (53.1%), hypertension (46.9%), obesity (46.2%), and diabetes mellitus (32.4%). Comparisons between the 2 groups showed that the risk factors, except for hypertension, were significantly higher in the Egyptian patients, despite the older age of the Americans (mean, 65.5 years; range, 22 to 88 years). The prevalence of triple-vessel disease was 86.6% in the Egyptian patients and 51.0% in the American patients (p < 0.001). The operative morbidity rates in the Egyptian patients were low: these included arrhythmias (13.8%), bleeding (13.4%), infection (7.6%), low cardiac output (3.4%), myocardial infarction (3.4%), and cerebrovascular accident (1.4%). The hospital mortality rate was 1.4% for the Egyptians and 1.7% for the Americans (NS). These results show that, despite the high prevalence of risk factors among Egyptian patients with coronary artery disease, coronary artery bypass grafting can be performed with low operative morbidity and mortality rates.

Hibernating myocardium is a potentially reversible form of left ventricular (LV) dysfunction the treatment of which improves function and prognosis. The identification of viable myocardium is critical in deciding which patients undergo revascularisation. Stunning is a clinically relevant phenomenon and it has been suggested that repeated episodes of stunning may cause chronic LV dysfunction. If this is the case then pharmacological agents which prevent stunning could represent a potential treatment of chronic LV dysfunction in patients with CAD.

This report describes a technique for removal of a segmental broken intramedullary femoral rod. Using a closed, stacked wire technique, removal of the broken hardware can be accomplished in a relatively easy and expeditious manner.

Transesophageal echocardiography and 2-dimensional transthoracic echocardiography have proved to be extremely valuable in the diagnosis of cardiac masses. In this report, we review the echocardiographic findings, clinical history, and histopathologic findings in 21 patients with intracardiac masses who underwent transthoracic echocardiography, transesophageal echocardiography, or both, at our institution. Of these patients, 14 had benign masses and 7 had malignant tumors. The potential role of transesophageal echocardiography in the diagnosis and treatment of patients with intracardiac masses is discussed. We believe that transesophageal echocardiography offers the cardiologist and cardiovascular surgeon the capability of more accurate preoperative and intraoperative assessment of cardiac masses.

Summary A 40 year old woman presented with dysphagia which was due to one of the forms of vascular ring. Her symptoms were relieved by relatively conservative surgery. The means of diagnosis and the surgical approach are discussed.

Acute gastric volvulus occurred in nine infants and one older child during the past 19 years; all patients had an associated left diaphragmatic anomaly. There were seven examples of eventration of the diaphragm, two of giant hiatal hernia and one Bochdalek hernia. Nine of the ten patients presented with vomiting and one with acute respiratory distress. The gastric volvulus was mesenteroaxial in eight patients and organoaxial in two. Operative treatment consisted of repair of the diaphragmatic anomaly and gastric fixation in eight patients. Gastric fixation alone was performed in one patient. A single patient died preoperatively and had gastric necrosis at postmortem examination. Of the nine patients treated operatively, all remain alive and well without recurrence. Acute gastric volvulus should be considered in any infant presenting with unexplained vomiting in association with a left diaphragm anomaly, and once diagnosed, immediate operation is mandatory.

Forty percent of 7.4 million Americans aged 80 years and older have symptomatic heart disease. Controversy exists as to whether the health care resources allotted to this patient subset represent a cost-effective approach to attaining a meaningful quality of life. Although aortic valve surgery carries greater risks in older than in younger patients, published studies reveal that the elderly should not be denied this procedure.To determine the results of aortic valve replacement (AVR) in an elderly population, we retrospectively analyzed 171 consecutive patients aged 80 to 91 years (mean, 82.6 years; 86 men and 85 women) who underwent AVR at the Texas Heart Institute between 1975 and 1991. Seventy-seven patients had AVR only, and 94 patients had concomitant surgical procedures (coronary artery bypass graft surgery, 75 patients; mitral valve replacement, mitral valve repair, aneurysm repair, 19 patients). The overall 30-day early mortality was 17.5%. The early mortality was 5.2% for patients with AVR only and 27.7% for those with concomitant surgical procedures. Statistical analysis of 17 perioperative variables revealed that left ventricular ejection fraction of less than 45%, hypertension, congestive heart failure, angina, and concomitant surgical procedures were significant univariate predictors of early mortality. Multivariate analysis revealed that left ventricular ejection fraction of less than 45%, hypertension, and concomitant surgical procedures were independent predictors of operative mortality. Mean follow-up of survivors was 39 months. The overall actuarial survival at 1, 3, and 5 years was 90.8%, 84.2%, and 76.0%, respectively.These results show that AVR can be performed with acceptable operative risks in the elderly. This study further shows that isolated AVR can be done with low operative mortality and that the performance of concomitant surgical procedures exposes elderly patients to higher operative risks.

The development of late tricuspid regurgitation following mitral valve replacement is accompanied by a severe reduction in exercise capacity and a poor functional outcome. In this study, we compared the clinical and echocardiographic characteristics of two matched groups with (n = 13) and without (n = 13) clinically significant tricuspid regurgitation. The preoperative pulmonary artery pressures and symptom durations were similar, but tricuspid regurgitation at palpation was detected only in patients who later developed severe tricuspid regurgitation (5/13 vs. 0/13; p0.02). None of the patients had echocardiographic evidence of rheumatic tricuspid valve disease at the time of the study, but the tricuspid annular diameter (3.7 +/- 0.5 cm vs. 3.2 +/- 0.4 cm; p0.05) and right ventricular diameter (4.9 +/- 0.4 cm vs. 4.0 +/- 0.8 cm; p0.01) were greater in patients who had developed severe late tricuspid regurgitation. Echocardiographic parameters of left ventricular function and Doppler estimated pulmonary artery systolic pressures were similar in the two groups, and no evidence of prosthetic dysfunction or aortic valve disease was found. These results imply that late tricuspid regurgitation following mitral valve replacement develops as a result of dilation of the tricuspid annulus associated with right ventricular decompensation. The persistence of uncorrected tricuspid incompetence would seem to be an important contributory factor, and its accurate detection and correction at the time of initial surgery may prove to be the most effective means of preventing the development of this important complication of mitral valve replacement.

The development of late tricuspid regurgitation is an important complication of mitral valve surgery, as it is associated with a severe impairment of exercise capacity and a poor symptomatic outcome. The pathogenesis of this condition remains poorly defined, but it is usually attributable to a functional abnormality of the tricuspid valve. Whilst its development may indicate an increased afterload on the right heart as a consequence of persistent pulmonary hypertension, mitral prosthetic dysfunction, progressive aortic valve disease or left ventricular failure, late tricuspid regurgitation may also develop in the absence of these factors and then may reflect right ventricular dysfunction and/or a localized abnormality of the tricuspid anulus. Failure to recognize and correct tricuspid regurgitation at the time of initial surgery may also account for many cases of tricuspid regurgitation but its re-appearance following tricuspid annuloplasty is uncommon and usually reflects a failure of the mitral prosthesis. A reduction in the prevalence of late tricuspid regurgitation is an important objective in view of the high operative mortality and disappointing long term results associated with reoperation for tricuspid regurgitation. This may be best achieved through combining earlier mitral valve surgery with the accurate detection and liberal correction of accompanying tricuspid incompetence at the time of initial surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Limited Doppler echocardiographic data are available regarding velocities and gradients across normally functioning St. Jude Medical valves in the aortic position. To establish a standard reference for Doppler characteristics of normal aortic St. Jude Medical prostheses, we recorded continuous-wave Doppler measurements of peak and mean velocities and peak and mean gradients in 180 patients with normally functioning St. Jude aortic valves. There were 119 men and 61 women in the study; the mean age was 57 years. Minimal valvular regurgitation was present in 56 patients (31 percent). Velocities and gradients were reported in five patient groups according to valve sizes of 19 mm, 21 mm, 23 mm, 25 mm, and 27 mm; the mean gradients were 16 +/- 6, 16 +/- 6, 14 +/- 5, 12 +/- 5, and 12 +/- 6, respectively. Differences in velocities and gradients among the five valve sizes were not statistically significant (p = 0.05). Velocities and gradients were also analyzed in three patient groups according to time intervals after valve replacement. The first group (n = 64) underwent Doppler evaluation one to seven days postoperatively (mean, six days); the second group (n = 60) was evaluated after 8 to 30 days postoperatively (mean, 12 days); and the third group (n = 56) was evaluated after more than 30 days postoperatively (mean, 691 days). There were no significant differences in measurements for the three groups.