Flow-mediated dilatation of the brachial artery is a poorly reproducible indicator of microvascular function in Type I diabetes mellitus.

BACKGROUND: Flow-mediated dilatation (FMD) of the brachial artery is commonly measured as a surrogate marker of endothelial function. Its measurement is, however, technically demanding and reports regarding its reproducibility have not always been favourable. AIM: Two Type I diabetes and control group comparator studies were conducted to assess the reproducibility of FMD and to analyse blood flow data normally discarded during FMD measurement. DESIGN: The studies were sequential and differed only with regard to operator and ultrasound machine. Seventy-two subjects with diabetes and 71 controls were studied in total. METHODS: Subjects had FMD measured conventionally. Blood velocity waveforms were averaged over 10 pulses post forearm ischaemia and their component frequencies analysed using the wavelet transform, a mathematical tool for waveform analysis. The component frequencies were grouped into 11 bands to facilitate analysis. RESULTS: Subjects were well-matched between studies. In Study 1, FMD was significantly impaired in subjects with Type I diabetes vs. controls (median 4.35%, interquartile range 3.10-4.80 vs. 6.50, 4.79-9.42, P < 0.001). No differences were detected between groups in Study 2, however. However, analysis of blood velocity waveforms yielded significant differences between groups in two frequency bands in each study. CONCLUSION: This report highlights concerns over the reproducibility of FMD measures. Further work is required to fully elucidate the role of analysing velocity waveforms after forearm ischaemia.

Comparison of rootMUSIC and discrete wavelet transform analysis of Doppler ultrasound blood flow waveforms to detect microvascular abnormalities in type I diabetes.

The earliest signs of cardiovascular disease occur in microcirculations. Changes to mechanical and structural properties of these small resistive vessels alter the impedance to flow, subsequent reflected waves, and consequently, flow waveform morphology. In this paper, we compare two frequency analysis techniques: 1) rootMUSIC and 2) the discrete wavelet transform (DWT) to extract features of flow velocity waveform morphology captured using Doppler ultrasound from the ophthalmic artery (OA) in 30 controls and 38 age and sex matched Type I diabetics. Conventional techniques for characterizing Doppler velocity waveforms, such as mean velocity, resistive index, and pulsatility index, revealed no significant differences between the groups. However, rootMUSIC and the DWT provided highly correlated results with the spectral content in bands 2-7 (30-0.8 Hz) significantly elevated in the diabetic group (p < 0.05). The spectral distinction between the groups may be attributable to manifestations of underlying pathophysiological processes in vascular impedance and consequent wave reflections, with bands 5 and 7 related to age. Spectral descriptors of OA blood velocity waveforms are better indicators of preclinical microvascular abnormalities in Type I diabetes than conventional measures. Although highly correlated DWT proved slightly more discriminatory than rootMUSIC and has the advantage of extending to subheart rate frequencies, which may be of interest.

Colour Doppler ultrasound of the ocular circulation in patients with systemic lupus erythematosus identifies altered microcirculatory haemodynamics.

We assessed whether quantitative analysis of Doppler flow velocity waveforms is able to identify subclinical microvascular abnormalities in SLE and whether eigenvector analysis can detect changes not detectable using the resistive index (RI). Fifty-four SLE patients with no conventional cardiovascular risk factors, major organ involvement or retinopathy were compared to 32 controls. Flow velocity waveforms were obtained from the ophthalmic artery (OA), central retinal artery (CRA) and common carotid artery (CA). The waveforms were analysed using eigenvector decomposition and compared between groups at each arterial site. The RI was also determined. The RI was comparable between groups. In the OA and CRA, there were significant differences in the lower frequency sinusoidal components (P < 0.05 for each component). No differences were apparent in the CA between groups. Eigenvector analysis of Doppler flow waveforms, recorded in proximity of the terminal vascular bed, identified altered ocular microvascular haemodynamics in SLE. Altered waveform structure could not be identified by changes in RI, the traditional measure of downstream vascular resistance. This analytical approach to waveform analysis is more sensitive in detecting preclinical microvascular abnormalities in SLE. It may hold potential as a useful tool for assessing disease activity, response to treatment, and predicting future vascular complications.

Root-MUSIC analysis of nitric oxide-mediated changes in ophthalmic artery blood flow velocity waveforms.

Clinical and experimental studies indicate that structural and functional changes in the microvasculature can predate or accompany risk factors for cardiovascular disease at the earliest stages in the disease process. In the current work, both simulated and actual Doppler ultrasound maximum blood velocity waveform envelopes recorded from the ophthalmic artery were analysed using a root-MUSIC and least squares fitting approach to determine amplitude frequency spectra. Both amplitude and frequency components of noise contaminated simulated waveforms were reliably determined indicating the robustness of the technique. The technique was then used to compare the spectral content of the ophthalmic artery blood velocity waveforms of normal controls in three test states: at baseline, following administration of GTN, a nitric oxide donor, and following administration of L-Name, a nitric oxide inhibitor. Principal components derived from root-MUSIC analysis discriminated between waveforms in baseline and non-baseline test states (p<0.00001) and between GTN and non-GTN test states (p=0.0002).

Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register.

OBJECTIVE: To assess the relative risk of major congenital malformation (MCM) from in utero exposure to antiepileptic drug (AEDs). METHODS: Prospective data collected by the UK Epilepsy and Pregnancy Register were analysed. The presence of MCMs recorded within the first three months of life was the main outcome measure. RESULTS: Full outcome data were collected on 3607 cases. The overall MCM rate for all AED exposed cases was 4.2% (95% confidence interval (CI), 3.6% to 5.0%). The MCM rate was higher for polytherapy (6.0%) (n = 770) than for monotherapy (3.7%) (n = 2598) (crude odds ratio (OR) = 1.63 (p = 0.010), adjusted OR = 1.83 (p = 0.002)). The MCM rate for women with epilepsy who had not taken AEDs during pregnancy (n = 239) was 3.5% (1.8% to 6.8%). The MCM rate was greater for pregnancies exposed only to valproate (6.2% (95% CI, 4.6% to 8.2%) than only to carbamazepine (2.2% (1.4% to 3.4%) (OR = 2.78 (p<0.001); adjusted OR = 2.97 (p<0.001)). There were fewer MCMs for pregnancies exposed only to lamotrigine than only to valproate. A positive dose response for MCMs was found for lamotrigine (p = 0.006). Polytherapy combinations containing valproate carried a higher risk of MCM than combinations not containing valproate (OR = 2.49 (1.31 to 4.70)). CONCLUSIONS: Only 4.2% of live births to women with epilepsy had an MCM. The MCM rate for polytherapy exposure was greater than for monotherapy exposure. Polytherapy regimens containing valproate had significantly more MCMs than those not containing valproate. For monotherapy exposures, carbamazepine was associated with the lowest risk of MCM.

A computerised system of screening for deep venous thrombosis.

We have developed a computer controlled system of strain gauge plethysmography for use as a screening tool for proximal segment venous thrombi which is simple to use, well tolerated by patients and extremely accurate. The computerised test was evaluated in 171 limbs of 163 symptomatic patients by comparison with subsequent ascending venography. Each of twenty occlusive proximal segment thrombi were identified, one non occlusive thrombus screened normal giving an overall sensitivity of 95.2%. The specificity of the test was 80% with a negative predictive value of 99.0%. The computerised system allows accurate screening for proximal segment venous thrombosis, and may permit more selective use of venography in the symptomatic post-operative limb.

Impedance plethysmography. A noninvasive screening method to detect deep-vein thrombosis.

Impedance plethysmography (IPG) is a useful noninvasive detection of proximal segment thrombosis. Seven hundred patients treated with total hip arthroplasty were examined preoperatively and several times postoperatively using this technique. Twenty-one abnormal IPG results were obtained, and venography confirmed that 12 of these patients had proximal segment thrombi and five had evidence of calf thrombi. Four venograms were completely clear, demonstrating a false-positive rate of 1.3% (including calf thrombi). Six patients with normal IPG results had calf thrombi. All positive venograms indicating a thrombus in the proximal venous segment were indicated with a positive IPG result, giving a sensitivity of 100%. The standardization of the procedure involving constant leg elevation has assisted in the accuracy of this screening system.