High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism

BACKGROUND: Established risk factors, including deficiencies of protein C, protein S or antithrombin and the factor V Leiden and prothrombin mutation, are present in about one third of unselected patients with venous thromboembolism. In addition to these inherited thrombophilic defects, elevated plasma levels of factor VIIIc have been suggested to be important in the pathogenesis of (recurrent) venous thromboembolism. The objective of this study was to assess the relevance of factor VIIIc plasma concentration in consecutive patients with venous thromboembolism. METHOD: We studied the prevalence of elevated plasma levels of factor VIIIc in 65 patients with a proven single episode and in 60 matched patients with documented recurrent venous thromboembolism. The reference group consisted of 60 age- and sex-matched patients who were referred for suspected venous thromboembolism, which was refuted by objective testing and long-term clinical follow-up. To minimalize the influence of the acute phase, blood was obtained at least 6 months after the thromboembolic event and results were adjusted for fibrinogen and C-reactive protein. Factor VIIIc was re-determined several years after the first measurement in a subset of patients to evaluate the variability over time. To study a possible genetic cause, a family study was done. FINDINGS: In the control, single and recurrent episode group, the prevalences of plasma levels of factor VIIIc above 175 IU/dl (90th percentile of controls) were 10% (95% CI: 4 to 21%), 19% (95% CI: 10 to 30%) and 33% (95% CI: 22 to 47%), respectively. For each 10 IU/dl increment of factor VIIIc, the risk for a single and recurrent episode of venous thrombosis increased by 10% (95% CI: 0.9 to 21%) and 24% (95% CI: 11 to 38%), respectively. Both low and high plasma levels of factor VIIIc were consistent over time (R = 0.80, p = 0.01). A family study indicated a high concordance for elevated factor VIIIc plasma concentrations among first degree family members. Adjustment for fibrinogen, C-reactive protein and known thrombophilic risk factors did not change the observed association of elevated factor VIIIc with thrombosis. INTERPRETATION: Elevated plasma levels of factor VIIIc are a significant, prevalent, independent and dose-dependent risk factor for venous thromboembolism. It also predisposes to recurrent venous thromboembolism.     

Prevalence and aetiology of neurological impairment in extremely low birthweight infants

Objective : To determine the prevalence and perinatal predictors of cerebral palsy, intellectual impairment, visual impairment and deafness in a cohort of extremely low birthweight (ELBW) infants at two years of age.
Methodology : The study population comprised 199 of the 224 (89%) ELBW infants managed at the Mater's Mothers Hospital, Brisbane, between July 1977 and February 1990 and who survived to two years. The prevalence of cerebral palsy, intellectual impairment, blindness and deafness was measured by clinical, psychometric and audiological assessment and the association with 24 risk factors examined.
Results : Cerebral palsy occurred in 20 children (10%). Risk of cerebral palsy was associated with ventricular dilatation, intraventricular haemorrhage, necrotizing enterocolitis and multiple birth, though only ventricular dilatation (OR 4.41; 95% Cl 1.32-14.8) remained significant in the adjusted analysis. Intellectual impairment occurred in 20 children (10%) and was independently associated with ventricular dilatation (OR 15.0; 95% Cl 2.2-102.8), ventilation F _iO₂ >80% (OR 3.4; 95% Cl 1.01-11.5), vaginal delivery (OR 3.5; 95% Cl 1.09-11.4) and male sex (OR 6.1; 95% Cl 1.67-22.3). No perinatal predictor was statistically associated with risk of deafness. Retinopathy of prematurity (OR 36.9; 95% Cl 2.8-495.5) was associated with risk of later visual impairment.
Conclusions : Intellectual impairment was associated with a broad range of perinatal variables. Cerebral palsy was associated with fewer variables, all of which were also associated with intellectual impairment. Neurologic injury was associated with male sex and multiple birth, which are not biological insults themselves, but may be markers of susceptibility to injury.     

Protein nutrition, faecal flora and iron metabolism: the role of milk-based formulae

This paper explores the role of milk-based formulae in achieving four aspects of nutritional health in infants and toddlers: in the suckling, to mimic the amino acid metabolism and the faecal flora of a breast-fed baby; in the weanling, to achieve adequate protein intakes in later infancy and beyond and to achieve satisfactory haemoglobin concentrations in the early toddler years. Milk-based formulae have two roles in infant nutrition: as so-called breast milk substitutes and as a safety net during the weaning period; the latter role may be the more important.     

Spatiotemporal Effects of Syncytial Heterogeneities on Cardiac Far-Field Excitations During Monophasic and Biphasic Shocks

Far-Field Excitation Via Syncytial Heterogeneities. Introduction: It has recently been postulated that syncytial (anatomic) heterogeneities inherent within cardiac tissue might represent a significant mechanism underlying field-induced polarization of the bulk myocardium. This simulation study examines and characterizes the spatiotemporal excitatory dynamics associated with this newly hypothesized mechanism. Methods and Results: Two-dimensional regions of syncytially heterogeneous cardiac tissue were simulated with active membrane kinetics. Heterogeneities were manifested via random spatial variations of intracellular volume fractions over multiple length scales. Excitation thresholds were determined for uniform rectangular monophasic (M) and symmetric biphasic (B) far-field stimuli, from which strength-duration and strength-interval relationships were constructed. For regions measuring 5.4 × 5.4 mm, baseline diastolic thresholds for longitudinal (L) and transverse (T) shocks of 5-msec total duration averaged (in V/cm, n = 10) M-L = 2.87 ± 0.26. M-T = 6.71 ± 0.83, B-L = 3.22 ± 0.25, and B-T = 7.93 ± 0.51. These thresholds decreased by 15% to 25% when the region sizes were increased to 10.8 × 10.8 mm. Strength-duration relationships correlated strongly with the Weiss-Lapicque hyperbolic relationship, with rheobases and chronaxies of 2.33 V/cm and 1.15 msec for M-L stimuli, and 2.28 V/cm and 2.04 msec for B-L stimuli. Strength-interval relationships for M-I. and B-L stimuli decreased monotonically with increasing coupling intervals, with similar minimum coupling intervals at absolute refractoriness. However, the B-L thresholds were substantially less sensitive to changes in coupling intervals than their M-L counterparts. Conclusion: This study provides strong additional support for and understanding of the syncytial heterogeneity hypothesis and its manifested properties. Furthermore, these results predict that syncytial heterogeneities of even modest proportions could represent a significant mechanism contributing to the far-field excitation process.     

Modulation of Healthy Pig Coronary Arteries by Self-Expanding Stents

Objectives: To evaluate the expansion ratio of a self-expanding stem over time, and the chronic effect of stent pressure on the vessel wall . Methods: Self-expanding stents, developed by Medtronic Inc. (Minneapolis, MN, USA) and the Rouen group (Letac, Cribier, France), were implanted in 21 normal pig coronary arteries. Animals were sacrificed after recatheterization at 1 day (group I, n = 4), I week (group 2, n = 3), 3 weeks (group 3, n = 5), or 8 weeks (group 4, n = 4). Histological morphometry of the vessel medial and neointimal layers was performed. Changes were related to the, stent diameter and. its force on the vessel wall . Results: The stent expansion ratio gradually increased from 73% to 93% after 8 weeks, which implicates that radial force decreased concomitantly from 0.10 N to 0.03 N. Media compression under the rods ranged from 4l%-66% immediately after stent implantation. The mean compression was unrelated to stent expansion and remained nearly the same (40%-50%) during follow-up. Individual media rod compression ranged from 5%-95%. The neointimal layer on top of the rods increased until the third week after stent implant (neointimal thickness 211 ± 108 μm). The layer significantly decreased at 8 weeks (neointimal thickness 65 ± 9 μm). The cross-sectional neointimal area increased gradually only at the end of the stent during the 8-week follow-up . Conclusions: The self-expanding stent implanted in normal pig coronary arteries reached a gradual relaxation state 8 weeks after implantation due to the persistent radial force. This radial force induces medial wall compression, which was only positively related to the thickness of the neointimal layer at 3 weeks after implant . (J Interven Cardiol 1996;9:45–52)     

Multiplane Transthoracic Echocardiography: Image Orientation, Anatomic Correlation, and Clinical Experience with a Prototype Phased Array Multiplane Surface Probe

Multiplane transthoracic echocardiography provides numerous sequential images by rotation of the transducer imaging array through 180° with the surface probe at a fixed site. We explored the potential of this new technique with a 3.7/5-MHz prototype multiplane transthoracic probe. Echoanatomic correlations were first examined in ten explanted hearts. The transducer was then applied in 30 normal humans at transthoracic acoustic windows to determine the imaging planes available. Use of this probe in 76 patients with various cardiac disorders indicated that this probe eases the procedure of transthoracic echocardiographic examination, provides incremental information for improved delineation and understanding of cardiac pathology, and yields many novel insights to echocardiographic interpretation. Multiplane transthoracic echocardiography appears to expand the versatility of transthoracic two-dimensional echocardiography.