Chronic kidney damage in the adult Fontan population.

OBJECTIVES: 1) To determine the accuracy of estimated GFR (eGFR) as compared to directly measured GFR (mGFR) in the adult Fontan population; 2) to determine the true prevalence of chronic kidney damage (CKD) as determined by uACR AND eGFR. METHODS: Prospective study of 81 patients Fontan patients (≥18years) followed at St. Paul's Hospital, University of British Columbia. CKD-EPI and MDRD equations used to calculate eGFR, mGFR determined by 99mTc-DTPA renal dynamic imaging and urine albumin to creatinine ratios were calculated. RESULTS: The mGFR was 93±27ml/min/1.73m2: 28 (53%) had an mGFR<90ml/min/1.73m2 and 1 (2%) had an mGFR <60ml/min/1.73m2. There was a modest correlation between mGFR and eGFR (EPI/MDRD) (r=0.50, p<0.0001 and r=0.54, p<0.0001 respectively). Both eGFR (EPI) (bias 27.0; 95% CI 18.0-27.7ml/min/m2, p<0.0001) and eGFR (MDRD) (bias 15.5; 95% CI 7.6-17.4ml/min/m2, p<0.0001) overestimated GFR as compared to mGFR. Among patients with an eGFR (EPI)/(MDRD) >90ml/min/1.73m2, 50% and 46% respectively had an mGFR <90ml/min/1.73m2. Significant albuminuria (>3mg/mmol) was present in 33% and upwards of 32% of patients with a normal eGFR (MDRD/EPI) had evidence of CKD with uACR >3mg/mmol. Using combined criteria of eGFR <90ml/min/1.73m2 and/or uACR >3mg/mmol, 46% of patients had evidence of CKD. CONCLUSIONS: This study draws attention to the need for stringent CKD screening as an important proportion of CKD is currently not being detected. Mild undetected CKD, an early marker of end organ damage, may also be an early sign of Fontan failure that requires warrants further research.

Longitudinal sequential biventricular assessment in adults with transposition of the great arteries and relationship with adverse outcomes.

BACKGROUND: In a cohort of congenitally corrected transposition of the great arteries (cc-TGA) and transposition of the great arteries after atrial switch procedure (d-TGA) the study objectives were: 1) to assess the change of quantitative systemic right ventricle (sRV) parameters over time and; 2) to examine the relationship of quantitative sRV parameters with adverse clinical outcomes. METHODS AND RESULTS: Single-center cohort study that included 49 (39%) cc-TGA and 76 (61%) d-TGA patients >18years who had at least one MUGA sRV assessment, 18/39 had more than one respectively. The primary clinical endpoint was all-cause mortality, heart transplantation and/or heart failure hospitalization. At a median clinical follow-up of 7years following the first MUGA, the primary endpoint occurred more often in cc-TGA versus d-TGA patients (18 (36.7%) vs. 9 (11.8%), p=0.03). Median time between the MUGA assessments was 5.8 (cc-TGA) and 4.9years (d-TGA). At last MUGA follow-up: 6 (33%) cc-TGA/14 (36%) d-TGA patients showed a significant decline in sRVEF (>5%); 6 (33%) cc-TGA/17 (44%) d-TGA patients had a significant increase in sRVEDVi; and 7 (39%) cc-TGA/19 (49%) PA-TGA patients had a significant increase in sRVESVi. Baseline sRV parameters were not associated with the primary end point or sRV changes over time. CONCLUSIONS: An important proportion of both patient cohorts demonstrated a significant change in sRV parameters over time and these are likely related to multiple factors that vary between individuals given population heterogeneity. The TGA patients have distinct clinical trajectories with increased adverse heart failure outcomes in the cc-TGA population and sRV parameters were not related to adverse heart failure events in either group.

Wearable embroidered muscle activity sensing device for the human upper leg.

Within the last decade, running has become one of the most popular physical activities in the world. Although the benefits of running are numerous, there is a risk of Running Related Injuries (RRIs) of the lower extremities. Electromyography (EMG) techniques have previously been used to study causes of RRIs, but the complexity of this technology limits its use to a laboratory setting. As running is primarily an outdoors activity, this lack of technology acts as a barrier to the study of RRIs in natural environments. This study presents a minimally invasive wearable muscle sensing device consisting of jogging leggings with embroidered surface EMG (sEMG) electrodes capable of recording muscle activity data of the quadriceps group. To test the use of the device, a proof of concept study consisting of N = 2 runners performing a set of 5 km running trials is presented in which the effect of running surfaces on muscle fatigue, a potential cause of RRIs, is evaluated. Results show that muscle fatigue can be analysed from the sEMG data obtained through the wearable device, and that running on soft surfaces (such as sand) may increase the likelihood of suffering from RRIs.

Height and the risk of gestational diabetes: variations by race/ethnicity.

AIMS: Gestational diabetes is a common pregnancy complication affecting races/ethnicities disproportionally. Adult height, an indicator of both genetic and early-life factors, is inconsistently associated with gestational diabetes risk. We examined the association and whether it varies by races in a nationally representative US cohort. METHODS: Analyses were conducted among 135 861 pregnancies in the Consortium on Safe Labor, 5567 of which were diagnosed with gestational diabetes based on medical records review. Generalized estimating equations were used to estimate odds ratios (95% confidence intervals) of gestational diabetes, controlling for other risk factors including body weight. Additionally, a meta-analysis of 15 761 pregnancies with gestational diabetes and 205 828 without gestational diabetes was conducted to estimate the pooled mean difference in height between those with gestational diabetes and control subjects. RESULTS: Height was inversely associated with gestational diabetes risk across races/ethnicities, with the strongest association among Asians (P for interaction < 0.01). Comparing extreme quartiles (> 168 vs. < 157 cm), adjusted odds ratios (95% confidence intervals) were 0.18 (0.09-0.36) for Asians/Pacific Islanders, 0.33 (0.29-0.38) for non-Hispanic white women, 0.39 (0.31-0.51) for Hispanics and 0.59 (0.47-0.75) for non-Hispanic black women. Meta-analysis found women with gestational diabetes to be significantly shorter than others. CONCLUSIONS: Taller women are at lower risk of developing gestational diabetes, with the magnitude of association varying significantly across races/ethnicities.

OS029. Severe anemia, sickle cell disease, and thalassemia as riskfactors for preeclampsia in developing countries.

INTRODUCTION: Hypertensive disorders during pregnancy contribute greatly to maternal and perinatal morbidity and mortality in developing countries. The pathogenesis of such conditions may be illuminated by exploring their relationship to anemia. OBJECTIVES: To determine whether several types of anemia are risk factors for hypertensive disorders during pregnancy in developing countries. METHODS: Using data from the World Health Organization Global Survey for Maternal and Perinatal Health, collected in hospitals in six African and six Latin American countries from 2007 to 2008 and in four Asian countries from 2004 to 2005, we examined the associations between severe anemia, sickle cell disease and thalassemia and gestational hypertension or preeclampsia/eclampsia. After exclusions for comorbidities (chronic hypertension, diabetes, HIV infection) and missing data, the severe anemia, sickle cell disease, and thalassemia groups consisted of 219,627,117,383, and 9376 women, respectively. RESULTS: Multiparous women with severe anemia were at an increased risk of gestational hypertension (adjusted odds ratio (OR): 1.58; 95% confidence interval (CI): 1.15-2.19). Severe anemia had a significant association with preeclampsia/eclampsia for nulliparous (OR: 3.55; 95% CI: 2.87-4.41) and multiparous (OR: 3.94; 95% CI: 3.05-5.09) women. Sickle cell disease exhibited a significant association with gestational hypertension among nulliparous (OR: 2.49; 95% CI: 1.46-4.25) and multiparous (OR: 3.27; 95% CI: 2.33-4.58) women. No significant associations were found between sickle cell disease and preeclampsia/eclampsia, or between thalassemia and either gestational hypertension or preeclampsia/eclampsia. CONCLUSION: Severe anemia appears to be a risk factor for preeclampsia/eclampsia, while sickle cell disease appears to be a risk factor for gestational hypertension among women seeking hospital care in developing countries.

Does the individualized reference outperform a simple ultrasound-based reference applied to birth weight in predicting child neurodevelopment?

OBJECTIVES: Being small-for-gestational age (SGA) is associated with an increased risk of morbidity, but questions remain about how best to diagnose SGA, and thus, predict poor health consequences. The authors sought to compare an individualized reference for defining SGA with simple birth weight-based and ultrasound-based references applied to birth weight in predicting poor cognitive development at age five. METHODS: The authors used data from the Successive SGA Births Study, a prospective study including 699 Alabaman and 618 Scandinavian women recruited from 1986 to 1988, and whose children had cognitive development scores measured at age five using the Wechsler Preschool and Primary Scale of Intelligence-Revised Intelligence Quotient. Sensitivity, specificity and positive predictive value (PPV) were estimated for each reference applied to birth weight using adverse cognitive development (score < 10(th) percentile) as the outcome. Relative risk of poor neurodevelopment was calculated, comparing infants classified as SGA by either the individualized or the simple ultrasound-based reference with infants not classified as SGA. RESULTS: The individualized reference had higher specificity and PPV in predicting poor neurodevelopment. Neonates defined as SGA by the individualized reference alone had a higher risk (RR=2.20, 95% CI: 1.20, 4.00) of poor cognitive outcome, while those identified by the ultrasound-based reference alone did not (RR=0.95, 95% CI: 0.45, 2.01). None of the references could predict poor neurodevelopment well at age five. CONCLUSIONS: The individualized birth weight reference modestly outperforms the simple ultrasound-based reference in identifying SGA infants with poor child neurodevelopment. However, neither reference can predict child neurodevelopment well.

Diurnal variation of macular oedema in CRVO: prospective study.

INTRODUCTION: Patients with central retinal vein occlusion (CRVO) may experience reduced vision in the morning. This may be due to increased cystoid macular oedema (CMO), which can be measured on optical coherence tomography (OCT). METHODS: A prospective study was performed on ten patients. Retinal thickness measurements were made with the Topcon 3D OCT-1000: at 9 A.M., 11 A.M., 1 P.M., 3 P.M., 5 P.M. In addition, at 9 A.M. and 5 P.M. visual acuity was recorded using ETDRS LogMAR. RESULTS: There were seven males and three females with average age of 59.4 years (range 40-80 years). The average duration of symptoms was 5.4 months (range 3-9 months). In eyes with CRVO, median central macular thickness (CMT) significantly reduced from 571 microm at 9 A.M. to 475 microm at 5 P.M. (p < 0.05). Comparison of CMT at 9 A.M. to each of the subsequent time intervals found that there was a significant reduction in the central macula thickness late in the day (p < 0.05). There was no statistical difference in the visual acuity and change in macular thickness did not correlate with change in visual acuity in eyes affected by CRVO. DISCUSSION: Patients with CRVO demonstrate increase in CMO in morning compared with late morning and afternoon. Possible causes are diurnal variation in blood pressure, retinal metabolism and erect posture. Interventions designed to influence these factors could be used to try to reduce CMO severity.

Ophthalmic manifestations of acute leukaemias: the ophthalmologist's role.

With evolving diagnostic and therapeutic advances, the survival of patients with acute leukaemia has considerably improved. This has led to an increase in the variability of ocular presentations in the form of side effects of the treatment and the ways leukaemic relapses are being first identified as an ocular presentation. Leukaemia may involve many ocular tissues either by direct infiltration, haemorrhage, ischaemia, or toxicity due to various chemotherapeutic agents. Ocular involvement may also be seen in graft-versus-host reaction in patients undergoing allogeneic bone marrow transplantation, or simply as increased susceptibility to infections as a result of immunosuppression that these patients undergo. This can range from simple bacterial conjunctivitis to an endophthalmitis. Leukaemia can present as pathology in the adnexae, conjunctiva, sclera, cornea, anterior chamber, iris, lens, vitreous, retina, choroid, and optic nerve. Recognition of the varied ocular presentations is also important in assessing the course and prognosis of leukaemia. We have presented a systematic approach taking each part of the eye in turn and outlining how leukaemia has been shown to affect it.

Divergent strabismus fixus--a case report.

Strabismus fixus is a rare condition and usually is of convergent type in which one or both eyes are anchored in a position of extreme adduction. Convergent type strabismus fixus is considered to be a congenital disorder and a part of congenital extraocular muscle fibrosis syndrome. Villasecca and Martinez described an acquired type of strabismus fixus. Hayashi et al reported that progressive esotropia could develop into the acquired type of convergent strabismus fixus. There are very few reports of divergent strabismus fixus in the literature. It may or may not be accompanied by ptosis or generalized extraocular muscle fibrosis. In our report, a case of divergent type strabismus fixus is described and discussed.

Factors affecting haemolysin production and congo red binding in Salmonella enterica serovar Typhimurium DT 98.

Differences in haemolysin expression were observed in a strain of Salmonella enterica serovar Typhimurium definitive phage type (DT) 98 cultured under various conditions. Haemolysin expression was optimal in cultures grown micro-aerobically. The zones of haemolysis were wider after longer periods of incubation. Haemolysin production varied after growth in the following media (greatest to least): brain heart infusion (BHI) broth > nutrient broth (NB)>trypticase soy broth (TSB)> M-9 glucose medium. Haemolysin production correlated directly with Congo red binding in nutrient broth. On Congo red blood agar, colonies were smaller, with dark centres and wider zones of haemolysis. Culture-cell-free haemolysin activity was higher, but cell-bound haemolysin activity was very low in growth medium supplemented with Congo red. Boiled tea extract at 25% v/v (of 25% w/v tea infusion) in PBS and nutrient broth was bactericidal to S. Typhimurium DT 98. The addition of boiled tea extract to growth medium inhibited haemolysin production by S. Typhimurium DT 98 at higher concentrations (6-12.5% v/v) but stimulated haemolysin production at lower concentrations (1.5-3% v/v). The pre-treatment of bacterial cell suspensions with lower concentrations of tea extract (1.5-3% v/v) also altered the Congo red binding, which showed an inverse correlation in nutrient broth.

IGF-I, osteocalcin, and bone change in pregnant normotensive and pre-eclamptic women.

Pre-eclampsia is a pregnancy disorder of uncertain etiology that affects 5-10% of all pregnancies, with symptoms typically presenting around or after 20 wk gestation. We hypothesized that IGF-I, osteocalcin, and bone loss would be different among women with pre-eclampsia compared with normotensive pregnant women. There were 962 pregnant healthy women, aged 12-35, who were assessed at entry to care, at 28 wk, and at delivery for osteocalcin and IGF-I concentrations. Bone ultrasound was measured at entry to care and at 6 wk postpartum, whereas bone mineral density was measured by dual x-ray densitometry at delivery. There were 64 women (6.7%) among the women being followed who developed pre-eclampsia. In women with pre-eclampsia, IGF-I concentrations were 74% greater in the third trimester compared with the first trimester, whereas there was little change in osteocalcin concentrations. In contrast, normotensive women had an average increase of 43% in IGF-I concentrations accompanied by a 63% decline in osteocalcin concentrations. In women with pre-eclampsia, IGF-I and osteocalcin concentrations were significantly correlated (r = 0.48 and 0.43) at both the first and third trimester time points, but only in the third trimester among normotensive women (r = 0.27). The bone change difference between the two groups was not statistically significant. Women with pre-eclampsia appear to have an exaggerated IGF-I responsiveness compared with women who are normotensive; however, the strong correlation between IGF-I and osteocalcin in women with pre-eclampsia suggests that the IGF-I is able to retain its role as a local regulator of bone remodeling, as indicated by the osteocalcin concentrations.

Correlation between Congo red binding and contact haemolysin production in Shigella species.

Haemolytic strains of Shigella dysenteriae type 1, Shigella flexneri, Shigella boydii and Shigella sonnei cultured on Congo red agar produced pigmented colonies (Pcr+) whereas nonhaemolytic strains produced white colonies and did not bind Congo red (Pcr-). S. flexneri-1 haemolysin negative mutant (lacking plasmid) of haemolysin positive prototroph also did not bind Congo red and produced nonpigmented colonies. Among the twelve strains of Shigella included in this study, the characteristics of Congo red binding, plasmid profile and haemolytic activity appeared to be correlated. Congo red binding occurred comparatively more by haemolysin-producing strains. Congo red binding can be used as a quick and reliable method for virulence traits of pathogens, including haemolysin activity.

G protein-coupled receptors desensitize and down-regulate epidermal growth factor receptors in renal mesangial cells.

Different types of plasma membrane receptors engage in various forms of cross-talk. We used cultures of rat renal mesangial cells to study the regulation of EGF receptors (EGFRs) by various endogenous G protein-coupled receptors (GPCRs). GPCRs (5-hydroxytryptamine(2A), lysophosphatidic acid, angiotensin AT(1), bradykinin B(2)) were shown to transactivate EGFRs through a protein kinase C-dependent pathway. This transactivation resulted in the initiation of multiple cellular signals (phosphorylation of the EGFRs and ERK and activation of cAMP-responsive element-binding protein (CREB), NF-kappaB, and E2F), as well as subsequent rapid down-regulation of cell-surface EGFRs and internalization and desensitization of the EGFRs without change in the total cellular complement of EGFRs. Internalization of the EGFRs and the down-regulation of cell-surface receptors in mesangial cells were blocked by pharmacological inhibitors of clathrin-mediated endocytosis and in HEK293 cells by transfection of cDNA constructs that encode dominant negative beta-arrestin-1 or dynamin. Whereas all of the effects of GPCRs on EGFRs were dependent to a great extent on protein kinase C, those initiated by EGF were not. These studies demonstrate that GPCRs can induce multiple signals through protein kinase C-dependent transactivation of EGFRs. Moreover, GPCRs induce profound desensitization of EGFRs by a process associated with the loss of cell-surface EGFRs through clathrin-mediated endocytosis.

Usefulness of intravascular ultrasound in preventing stenting of hazy areas adjacent to coronary stents and its support of support spot-stenting.

The uncertain significance of hazy areas at the margins of coronary stents may lead to further, at times unnecessary, stenting. However, the risk of restenosis increases substantially when additional stents are deployed. We used intravascular ultrasound (IVUS) to identify the causes of hazy segments adjacent to stents. We identified 13 cases with hazy regions adjacent to coronary stents and 20 controls without hazy regions matched by age, gender, and vessel stented. Hazy regions were defined from the angiogram as reduced contrast density without a clearly defined intimal tear, dissection, thrombus, or stenosis (> 50%). IVUS images were obtained from the reference, stent, and hazy and control regions adjacent to the stent. Computerized planimetery was used to measure the vessel, lumen, and plaque cross-sectional areas (CSAs), the maximum arc of calcium, and the eccentricity ratio (minimum:maximum lumen diameter). There were no significant differences between hazy and control segments in the vessel, lumen, and plaque CSAs. All lumen CSAs were >4.0 mm2. Compared with control regions, the hazy regions had calcified plaque more often (69% vs 25%; odds ratio [OR] 6.75, 95% confidence intervals [CI] 1.82 to 25.0]) and more frequent intimal tears (23% vs 0%, OR 6.67, 95% CI 1.98 to 35.0). Haziness was particularly associated with calcified plaque and eccentric lumen (p = 0.037). Thus, haziness at the margins of coronary stents is often caused by calcified plaque. IVUS can differentiate calcified plaques from intimal tears and thereby obviate unnecessary stenting.

Multiplicity of mechanisms of serotonin receptor signal transduction.

The serotonin (5-hydroxytryptamine, 5-HT) receptors have been divided into 7 subfamilies by convention, 6 of which include 13 different genes for G-protein-coupled receptors. Those subfamilies have been characterized by overlapping pharmacological properties, amino acid sequences, gene organization, and second messenger coupling pathways. Post-genomic modifications, such as alternative mRNA splicing or mRNA editing, creates at least 20 more G-protein-coupled 5-HT receptors, such that there are at least 30 distinct 5-HT receptors that signal through G-proteins. This review will focus on what is known about the signaling linkages of the G-protein-linked 5-HT receptors, and will highlight some fascinating new insights into 5-HT receptor signaling.

Cellular immune responses in human neurocysticercosis.

Studies on the role of cell-mediated immune responses in human neurocysticercosis (NCC) are lacking. Various cell-mediated immune responses such as lymphocyte subpopulation, lymphocyte transformation to cysticercus antigens and cytokine profile were carried out in NCC patients. Lymphocyte transformation assays using larval antigens showed significantly higher (3)H-thymidine uptake. Immunophenotyping analysis showed an insignificant increase in B cells and a decrease in total T cells. However, there was a significant decrease (P < 0.05) in CD8+ T cells whereas there was no change in other cells like CD4+, HLA-DR+ and CD16+/CD56+. Cytokine profile revealed significantly higher (P < 0.01) production of Th1 cytokines (gamma-IFN and IL-2) using cysticercal antigens as stimulants for peripheral blood mononuclear cells, while there was no difference in IL-4 levels between NCC patients and healthy controls. The cytokine profile indicated the involvement of Th-1-like responses in NCC patients.