Plant traits controlling growth change in response to a drier climate.

Plant traits are increasingly being used to improve prediction of plant function, including plant demography. However, the capability of plant traits to predict demographic rates remains uncertain, particularly in the context of trees experiencing a changing climate. Here we present data combining 17 plant traits associated with plant structure, metabolism and hydraulic status, with measurements of long-term mean, maximum and relative growth rates for 176 trees from the world's longest running tropical forest drought experiment. We demonstrate that plant traits can predict mean annual tree growth rates with moderate explanatory power. However, only combinations of traits associated more directly with plant functional processes, rather than more commonly employed traits like wood density or leaf mass per area, yield the power to predict growth. Critically, we observe a shift from growth being controlled by traits related to carbon cycling (assimilation and respiration) in well-watered trees, to traits relating to plant hydraulic stress in drought-stressed trees. We also demonstrate that even with a very comprehensive set of plant traits and growth data on large numbers of tropical trees, considerable uncertainty remains in directly interpreting the mechanisms through which traits influence performance in tropical forests.

Amazonia trees have limited capacity to acclimate plant hydraulic properties in response to long-term drought.

The fate of tropical forests under future climate change is dependent on the capacity of their trees to adjust to drier conditions. The capacity of trees to withstand drought is likely to be determined by traits associated with their hydraulic systems. However, data on whether tropical trees can adjust hydraulic traits when experiencing drought remain rare. We measured plant hydraulic traits (e.g. hydraulic conductivity and embolism resistance) and plant hydraulic system status (e.g. leaf water potential, native embolism and safety margin) on >150 trees from 12 genera (36 species) and spanning a stem size range from 14 to 68 cm diameter at breast height at the world's only long-running tropical forest drought experiment. Hydraulic traits showed no adjustment following 15 years of experimentally imposed moisture deficit. This failure to adjust resulted in these drought-stressed trees experiencing significantly lower leaf water potentials, and higher, but variable, levels of native embolism in the branches. This result suggests that hydraulic damage caused by elevated levels of embolism is likely to be one of the key drivers of drought-induced mortality following long-term soil moisture deficit. We demonstrate that some hydraulic traits changed with tree size, however, the direction and magnitude of the change was controlled by taxonomic identity. Our results suggest that Amazonian trees, both small and large, have limited capacity to acclimate their hydraulic systems to future droughts, potentially making them more at risk of drought-induced mortality.

Drought stress and tree size determine stem CO2 efflux in a tropical forest.

CO2 efflux from stems (CO2_stem ) accounts for a substantial fraction of tropical forest gross primary productivity, but the climate sensitivity of this flux remains poorly understood. We present a study of tropical forest CO2_stem from 215 trees across wet and dry seasons, at the world's longest running tropical forest drought experiment site. We show a 27% increase in wet season CO2_stem in the droughted forest relative to a control forest. This was driven by increasing CO2_stem in trees 10-40 cm diameter. Furthermore, we show that drought increases the proportion of maintenance to growth respiration in trees > 20 cm diameter, including large increases in maintenance respiration in the largest droughted trees, > 40 cm diameter. However, we found no clear taxonomic influence on CO2_stem and were unable to accurately predict how drought sensitivity altered ecosystem scale CO2_stem , due to substantial uncertainty introduced by contrasting methods previously employed to scale CO2_stem fluxes. Our findings indicate that under future scenarios of elevated drought, increases in CO2_stem may augment carbon losses, weakening or potentially reversing the tropical forest carbon sink. However, due to substantial uncertainties in scaling CO2_stem fluxes, stand-scale future estimates of changes in stem CO2 emissions remain highly uncertain.

Stand dynamics modulate water cycling and mortality risk in droughted tropical forest.

Transpiration from the Amazon rainforest generates an essential water source at a global and local scale. However, changes in rainforest function with climate change can disrupt this process, causing significant reductions in precipitation across Amazonia, and potentially at a global scale. We report the only study of forest transpiration following a long-term (>10 year) experimental drought treatment in Amazonian forest. After 15 years of receiving half the normal rainfall, drought-related tree mortality caused total forest transpiration to decrease by 30%. However, the surviving droughted trees maintained or increased transpiration because of reduced competition for water and increased light availability, which is consistent with increased growth rates. Consequently, the amount of water supplied as rainfall reaching the soil and directly recycled as transpiration increased to 100%. This value was 25% greater than for adjacent nondroughted forest. If these drought conditions were accompanied by a modest increase in temperature (e.g., 1.5°C), water demand would exceed supply, making the forest more prone to increased tree mortality.

After more than a decade of soil moisture deficit, tropical rainforest trees maintain photosynthetic capacity, despite increased leaf respiration.

Determining climate change feedbacks from tropical rainforests requires an understanding of how carbon gain through photosynthesis and loss through respiration will be altered. One of the key changes that tropical rainforests may experience under future climate change scenarios is reduced soil moisture availability. In this study we examine if and how both leaf photosynthesis and leaf dark respiration acclimate following more than 12 years of experimental soil moisture deficit, via a through-fall exclusion experiment (TFE) in an eastern Amazonian rainforest. We find that experimentally drought-stressed trees and taxa maintain the same maximum leaf photosynthetic capacity as trees in corresponding control forest, independent of their susceptibility to drought-induced mortality. We hypothesize that photosynthetic capacity is maintained across all treatments and taxa to take advantage of short-lived periods of high moisture availability, when stomatal conductance (gs ) and photosynthesis can increase rapidly, potentially compensating for reduced assimilate supply at other times. Average leaf dark respiration (Rd ) was elevated in the TFE-treated forest trees relative to the control by 28.2 ± 2.8% (mean ± one standard error). This mean Rd value was dominated by a 48.5 ± 3.6% increase in the Rd of drought-sensitive taxa, and likely reflects the need for additional metabolic support required for stress-related repair, and hydraulic or osmotic maintenance processes. Following soil moisture deficit that is maintained for several years, our data suggest that changes in respiration drive greater shifts in the canopy carbon balance, than changes in photosynthetic capacity.

Detection and targeting of splicing deregulation in pediatric acute myeloid leukemia stem cells.

Pediatric acute myeloid leukemia (pAML) is typified by high relapse rates and a relative paucity of somatic DNA mutations. Although seminal studies show that splicing factor mutations and mis-splicing fuel therapy-resistant leukemia stem cell (LSC) generation in adults, splicing deregulation has not been extensively studied in pAML. Herein, we describe single-cell proteogenomics analyses, transcriptome-wide analyses of FACS-purified hematopoietic stem and progenitor cells followed by differential splicing analyses, dual-fluorescence lentiviral splicing reporter assays, and the potential of a selective splicing modulator, Rebecsinib, in pAML. Using these methods, we discover transcriptomic splicing deregulation typified by differential exon usage. In addition, we discover downregulation of splicing regulator RBFOX2 and CD47 splice isoform upregulation. Importantly, splicing deregulation in pAML induces a therapeutic vulnerability to Rebecsinib in survival, self-renewal, and lentiviral splicing reporter assays. Taken together, the detection and targeting of splicing deregulation represent a potentially clinically tractable strategy for pAML therapy.

Reversal of malignant ADAR1 splice isoform switching with Rebecsinib.

Adenosine deaminase acting on RNA1 (ADAR1) preserves genomic integrity by preventing retroviral integration and retrotransposition during stress responses. However, inflammatory-microenvironment-induced ADAR1p110 to p150 splice isoform switching drives cancer stem cell (CSC) generation and therapeutic resistance in 20 malignancies. Previously, predicting and preventing ADAR1p150-mediated malignant RNA editing represented a significant challenge. Thus, we developed lentiviral ADAR1 and splicing reporters for non-invasive detection of splicing-mediated ADAR1 adenosine-to-inosine (A-to-I) RNA editing activation; a quantitative ADAR1p150 intracellular flow cytometric assay; a selective small-molecule inhibitor of splicing-mediated ADAR1 activation, Rebecsinib, which inhibits leukemia stem cell (LSC) self-renewal and prolongs humanized LSC mouse model survival at doses that spare normal hematopoietic stem and progenitor cells (HSPCs); and pre-IND studies showing favorable Rebecsinib toxicokinetic and pharmacodynamic (TK/PD) properties. Together, these results lay the foundation for developing Rebecsinib as a clinical ADAR1p150 antagonist aimed at obviating malignant microenvironment-driven LSC generation.

The effect of prior bisphosphonate therapy on the subsequent therapeutic effects of strontium ranelate over 2 years.

UNLABELLED: Many osteoporotic women prescribed strontium ranelate have previously received bisphosphonates. Prior bisphosphonate use blunted the spinal bone mineral density (BMD) response for 6 months. Hip BMD was blunted to a degree for 2 years, although there was an overall increase in hip BMD in contrast to the heel where BMD did not increase. INTRODUCTION: Many osteoporotic women commenced on strontium ranelate have already received treatment with bisphosphonates. This study investigates whether prior bisphosphonate use impairs the subsequent therapeutic response to strontium ranelate. METHODS: Women were recruited who were either bisphosphonate naïve or currently receiving a bisphosphonate. All women received strontium ranelate and were followed up for 2 years. RESULTS: One hundred and twenty women were recruited. After 2 years, the bisphosphonate-naïve group had significant BMD increases of 8.9%, 6.0% and 6.4% at the spine, hip and heel, respectively. In the prior bisphosphonate group, BMD increased significantly at the spine (4.0%) and hip (2.5%) but not at the heel. At all time points at all sites, the BMD increase was greater in the bisphosphonate-naïve group. BMD at the spine did not increase during the first 6 months in the prior bisphosphonate group but then increased in parallel with the bisphosphonate-naïve group. In contrast, the difference between the two groups in hip BMD continued to increase throughout the 2 years. P1NP was suppressed in the prior bisphosphonate group for the first 6 months. CONCLUSIONS: After bisphosphonate exposure, the BMD response to strontium ranelate is blunted for only 6 months at the spine. At the hip, a degree of blunting was observed over 2 years, although there was an overall increase in hip BMD in contrast to the heel where no increase in BMD was observed.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

SUMMARY: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). CONCLUSION: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

The relationship between the pH value of a hydration solution and the biomechanical properties of Crosado-embalmed human iliotibial bands.

Determining the biomechanical properties of human tissues commonly involves the immersion or spraying of the tissues to maintain them in a hydrated state. However, the influence of the pH value of these solutions on the biomechanical properties of the tissues is not well understood. This study investigated the effects of the pH value on the biomechanical properties of the collagen-rich human iliotibial band (ITB). A total of 124 samples were allocated to polyethylene glycol (PEG) solutions of pH values between 3 and 13 for 24 h, which is a frequently used immersion time prior to biomechanical tests. After this, the samples were biomechanically tested in a uniaxial tensile testing setup using an established testing routine. Similarly, 69 samples were allocated to pH groups of 6, 7 and 8 and biomechanically tested after 1, 2 and 3 weeks. The cross-sectional area of all samples was determined after immersion into the PEG solutions for the specified time frames. In the 24-h experiment, the elastic modulus (pH 12: p ≤ 0.045; pH 13: p ≤ 0.020) and the ultimate tensile strength (pH 12: p ≤ 0.031; pH 13: p ≤ 0.026) of the pH groups 12 and 13 were significantly lower and their cross-sectional areas were higher (pH 12: p ≤ 0.005; pH 13: p ≤ 0.003) compared to several groups of acidic to alkaline pH values. There was no difference in the maximum forces between the different groups within a 24-h immersion time (p > 0.999). In the 3-week-test, a decrease of the ultimate tensile strength was noted between the 24-h and 3 week values for the pH groups 7 (p = 0.034) and 8 (p = 0.029). It is concluded that pH-dependent tissue swelling influences the cross-sectional area-dependent biomechanical properties of the human ITB. Therefore, the pH value of storage and hydration solutions for the preparation of biomechanical tests should be recorded. From a biomechanical perspective, the collagen stability of the human ITB is largely unaltered in PEG solutions with pH values between 3 and 13 over 24 h.

Obstetric and perinatal outcomes in pregnancies complicated by Type 1 and Type 2 diabetes: influences of glycaemic control, obesity and social disadvantage.

AIMS: To compare obstetric and perinatal outcomes in women with Type 1 and Type 2 diabetes and relate these to maternal risk factors. METHODS: Prospective cohort study of 682 consecutive diabetic pregnancies in East Anglia during 2006-2009. Relationships between congenital malformation, perinatal mortality and perinatal morbidity (large for gestational age, preterm delivery, neonatal care) with maternal age, parity, ethnicity, glycaemic control, obesity and social disadvantage were examined using bivariable and multivariate models. RESULTS: There were 408 (59.8%) Type 1 and 274 (40.2%) Type 2 diabetes pregnancies. Women with Type 2 diabetes were older (P < 0.001), heavier (P < 0.0001), more frequently multiparous (P < 0.001), more ethnically diverse (p < 0.0001) and more socially disadvantaged (P = 0.0004). Although women with Type 2 diabetes had shorter duration of diabetes (P < 0.0001) and better pre-conception glycaemic control [HbA(1c) 52 mmol/mol (6.9%) Type 2 diabetes vs. 63 mmol/l (7.9%) Type 1 diabetes; p < 0.0001), rates of congenital malformation and perinatal mortality were comparable. Women with Type 2 diabetes had fewer large-for-gestational-age infants (37.6 vs. 52.9%, P < 0.0008), fewer preterm deliveries (17.5 vs. 37.1%, P < 0.0001) and their offspring had fewer neonatal care admissions (29.8 vs. 43.2%, P = 0.001). Third trimester HbA(1c) (OR 1.35, 95% CI 1.09-1.67, P = 0.006) and social disadvantage (OR 0.80, 95% CI 0.67-0.98; P = 0.03) were risk factors for large for gestational age. CONCLUSIONS: Despite increased age, parity, obesity and social disadvantage, women with Type 2 diabetes had better glycaemic control, fewer large-for-gestational-age infants, fewer preterm deliveries and fewer neonatal care admissions. Better tools are needed to improve glycaemic control and reduce the rates of large for gestational age, particularly in Type 1 diabetes.

Personal experiences of women with diabetes who do not attend pre-pregnancy care.

AIMS: To explore the views of women who did not attend pre-pregnancy care (PPC), in particular their accounts of contraception, previous pregnancies and the influence of healthcare advice. METHODS: We conducted semi-structured interviews with 29 pregnant women (21 with Type 1 diabetes, eight with Type 2 diabetes) at three UK specialist diabetes antenatal clinics. Interviews explored women's journeys to becoming pregnant, including use of contraception, their views regarding diabetes and pregnancy and the factors which encouraged and discouraged them from attending PPC. RESULTS: All women had some understanding of the issues concerning diabetes during pregnancy, predominantly regarding the benefits of PPC (90%) and optimal glycaemic control (80%) and risks of malformation (48%) and macrosomia (35%). Most were not regularly using contraception (70%), having stopped deliberately (45%), become unintentionally less rigorous (28%) or experienced side effects/contraindications (14%). Knowledge concerning the risks of pregnancy (90%) and past pre-conception counselling (38%) did not encourage women to attend PPC, and neither did personal experience of miscarriage, malformation or stillbirth in women with previous poor pregnancy outcome (41%). Barriers included conceiving faster than anticipated (45%), fertility concerns (31%), negative experiences with health professionals (21%), desire for a 'normal' pregnancy (17%) and the logistics of attending (10%). CONCLUSIONS: More integrated diabetes and reproductive health/contraceptive advice, increased awareness of the potentially short time between stopping contraception and conception and more intensive support between pregnancies are required, particularly for women with previously poor outcomes. Research is also needed into how communication between health professionals and women with diabetes can be improved.

Altered resource availability and the population dynamics of tree species in Amazonian secondary forests.

Despite research demonstrating that water and nutrient availability exert strong effects on multiple ecosystem processes in tropical forests, little is known about the effect of these factors on the demography and population dynamics of tropical trees. Over the course of 5 years, we monitored two common Amazonian secondary forest species-Lacistema pubescens and Myrcia sylvatica-in dry-season irrigation, litter-removal and control plots. We then evaluated the effects of altered water and nutrient availability on population demography and dynamics using matrix models and life table response experiments. Our results show that despite prolonged experimental manipulation of water and nutrient availability, there were nearly no consistent and unidirectional treatment effects on the demography of either species. The patterns and significance of observed treatment effects were largely dependent on cross-year variability not related to rainfall patterns, and disappeared once we pooled data across years. Furthermore, most of these transient treatment effects had little effect on population growth rates. Our results suggest that despite major experimental manipulations of water and nutrient availability-factors considered critical to the ecology of tropical pioneer tree species-autogenic light limitation appears to be the primary regulator of tree demography at early/mid successional stages. Indeed, the effects of light availability may completely override those of other factors thought to influence the successional development of Amazonian secondary forests.

The DXL Calscan heel densitometer: evaluation and diagnostic thresholds.

The DXL Calscan (Demetech AB) is a new dual energy X-ray absorptiometry device for determining heel bone mineral density (BMD). The system is based on the standard technique of dual energy X-ray absorptiometry (DXA), using a fan beam configuration, but introduces an additional laser measurement of heel thickness intended to improve accuracy. We have examined the utility, in vitro and in vivo performance of the DXL Calscan and established triage thresholds based on the UK's National Osteoporosis Society guidelines on peripheral densitometry. The Calscan proved convenient, easy to use and was stable over time and within a range of operating temperatures. Short-term in vitro precision as %CV, with phantom repositioning, was 0.75% and long term precision 0.73%. Precision in vivo, determined from duplicate right heel scans of 67 subjects, was 1.19%. Effective radiation dose to the patient was <0.1 microSv per scan. 140 white females (70 osteoporotic and 70 non-osteoporotic), aged 55-70 years underwent scans of both heels. Subjects were defined as osteoporotic or non-osteoporotic on the basis of axial DXA (spine L2-L4 and total hip). Triage thresholds for reassurance-referral or referral-treatment were 0.391 g cm(-2) and 0.306 g cm(-2) for non-dominant and 0.395 g cm(-2), 0.294 g cm(-2) for dominant heel, respectively. The non-dominant heel proved slightly superior to the dominant for triage purposes. Of the seven non-osteoporotic subjects misclassified as osteoporotic by Calscan of either heel, six had severe axial osteopenia. If operated by trained personnel and used in appropriate populations exhibiting risk factors, the Calscan is well suited for use in the management of post-menopausal osteoporosis.

Malocclusion model of temporomandibular joint osteoarthritis in mice with and without receptor for advanced glycation end products.

OBJECTIVE: This study has two aims: 1. Validate a non-invasive malocclusion model of mouse temporomandibular joint (TMJ) osteoarthritis (OA) that we developed and 2. Confirm role of inflammation in TMJ OA by comparing the disease in the presence and absence of the receptor for advanced glycation end products (RAGE). DESIGN: The malocclusion procedure was performed on eight week old mice, either wild type (WT) or without RAGE. RESULTS: We observed TMJ OA at two weeks post-misalignment/malocclusion. The modified Mankin score used for the semi-quantitative assessment of OA showed an overall significantly higher score in mice with malocclusion compared to control mice at all times points (2, 4, 6 and 8 weeks). Mice with malocclusion showed a decrease in body weight by the first week after misalignment but returned to normal weight for their ages during the following weeks. The RAGE knock out (KO) mice had statistically lower modified Mankin scores compared to WT mice of the same age. The RAGE KO mice had statistically lower levels of Mmp-13 and HtrA1 but higher Tgf-ß1, as measured by immunohistochemistry, compared to WT mice at eight weeks post malocclusion. CONCLUSIONS: We demonstrate an inexpensive, efficient, highly reproducible and non-invasive model of mouse TMJ OA. The mechanical nature of the malocclusion resembles the natural development of TMJ OA in humans, making this an ideal model in future studies that aim to elucidate the pathogenesis of the disease leading to the discovery of a treatment. The RAGE plays a role in mouse TMJ OA.

Effect of intermittent compression therapy on bone mineral density in women with low bone mass.

Intermittent pneumatic compression has been shown to increase blood flow in the leg which, in turn, may improve BMD. We performed a pilot study to assess whether intermittent compression of the leg could improve BMD at the femoral neck. 37 postmenopausal women with low bone density T score < -1 at either hip or spine were recruited into the study of whom 24 completed. Women applied intermittent compression for 2 h a day for 6 months to each leg in turn. The study lasted 1 year. Women were also given daily 1 g of Calcium and 800 IU of vitamin D (Calcichew D 3 forte Shire, UK). Lumbar spine BMD decreased by 0.5% at 12 months compared with baseline (mean difference 0.005 g/cm(2), 95% C.I -0.2287 to 0.03459, P = 0.28). At 12 months the right femoral neck BMD increased by 3% compared with baseline (mean 0.811 +/- 0.08, P = 0.22), while the left increased 2% (0.783 +/- 0.06, P = 0.16). There was no change in BMD at the distal tibia or heels and no site effect of the compression. The fat mass decreased by 4.6% in the right leg and 5% in the left leg (P = 0.005 and 0.003, respectively). Tissue thickness did not change. The analysis of the interaction between the degree of exercise and change in BMD showed a statistically significant increase in right femoral neck BMD following 6 months of right leg intermittent compression, but only in women whose exercise was minimal (P = 0.029). This effect was not seen in the left femur possibly due to the reduced number of patients who completed the study in this group. These preliminary results indicate that intermittent pneumatic leg compression may have a role in osteoporosis prevention. It may provide a mean of inhibiting decline in femoral neck BMD, particularly in sedentary women.

A phantom based study on the effect of subject positioning on morphometric X-ray absorptiometry using the Lunar Expert-XL.

Morphometric X-ray absorptiometry (MXA) relies on accurate measurement of vertical dimensions of vertebrae from a lateral perspective. Deviations resulting from scoliotic curvature or poor patient positioning produce distortions of visible vertebral dimensions and may lead to analysis error. This study utilized a phantom developed at this centre to assess the effect of vertebral malalignment on the accuracy of the MXA technique on the Lunar Expert-XL. Measured vertebral heights were found to be consistently underestimated by an average of 3.7%. Precision ranged from 0.79% for anterior height measurement to 1.03% for middle height measurement. Vertebral malalignment was investigated as the effect of rotation around the anteroposterior, lateral and superoinferior axes. Rotation around the lateral axis produced little discernible effect. However, superoinferior axial rotation showed a change of more than two standard deviations in the mid/posterior ratios of biconcave vertebrae at comparatively small angles of rotation. Anteroposterior axial rotation produced an increase in observed height at small angles of rotation, and a rapid decrease in vertebral height as rotation increased. The results suggest that whilst kyphosis or lordosis of up to at least 5.8 degrees has a minimal effect on MXA, scoliosis of 4.6 degrees or above produces a distinctive effect on the defining crush height ratios.

Evaluation of coronary subclavian steal syndrome using sestamibi imaging and duplex scanning with observed vertebral subclavian steal.

Coronary subclavian steal is defined as retrograde blood flow from the myocardium through the internal mammary artery graft, secondary to a proximal subclavian artery stenosis. The incidence of this syndrome in patients undergoing internal mammary artery grafts for coronary artery bypass is estimated to be 0.44%. Angiography remains the definitive diagnostic test for confirming this condition. We describe a noninvasive method for evaluating coronary subclavian steal syndrome in a 57-year-old man, with a 50-55% subclavian stenosis confirmed by angiography. Noninvasive evaluation using duplex scanning demonstrated normal vertebral artery blood flow. Technetium 99m-sestamibi (99mTc) imaging confirmed a fixed anterolateral defect. When left-arm isometric exercise was employed, retrograde vertebral artery blood flow was observed by Doppler imaging. A repeat 99mTc-sestamibi study documented an increase in tracer distribution in the anterolateral defect confirming reperfusion of the myocardium through the left internal mammary artery graft. The use of duplex scanning and 99mTc-sestamibi may serve as an adjunct in evaluating coronary subclavian steal syndrome as well as documenting transient vertebral subclavian steal in this patient population.

Doppler ultrasound of the uteroplacental circulation as a screening test for severe pre-eclampsia with intra-uterine growth retardation.

Two hundred primiparae underwent continuous-wave Doppler investigation of the uteroplacental circulation at 18-20 weeks gestation as a possible screening test for hypertension in pregnancy. Seventy-five women with abnormal waveforms suggestive of high uteroplacental resistance were tested again at 24 weeks when 21 demonstrated a persistent abnormality. Only nine (43%) of these went on to have an uncomplicated pregnancy, as compared with 150 (84%) of the remainder. Seventeen (8.5%) of the women in the study developed a hypertensive disorder of pregnancy, five of whom had abnormal waveforms at 18-20 weeks and at 24 weeks. These five women had a more severe degree of hypertension with proteinuria or intra-uterine growth retardation, and two required clinical intervention before term. The remaining 12 women were delivered at term of average, or heavier than average babies. Doppler investigation of the uteroplacental circulation at 24 weeks may prove to be a sensitive screening test for later severe pre-eclampsia with intra-uterine growth retardation.