Normal Waveform Research Articles

VHDL Modeling for Classification of Power Quality Disturbance Employing Wavelet Transform, Artificial Neural Network and Fuzzy Logic

The identification and classification of voltage and current disturbances are important tasks in the monitoring and protection of power systems. Most power quality disturbances are non-stationary and transitory and both detection and classification have proved to be very demanding. New intelligent system technologies that use wavelet transforms, expert systems and artificial neural networks include some unique advantages regarding fault analysis. This paper presents a new approach to classifying six classes of signals: five types of disturbance including sag, swell, transient, fluctuation, interruption, and the normal waveform. The concept of discrete wavelet transform for feature extraction from the power disturbance signal, combined with an artificial neural network and incorporating fuzzy logic to offer a powerful tool for detecting and classifying power quality problems, is introduced. The system was modeled using VHDL, a hardware description language, followed by extensive testing and simulation to verify the functionality of the system that allows efficient hardware implementation of the same. The extensive simulation results confirm the feasibility of the proposed algorithm. This method proposed herein classified and obtained 98.19% classification accuracy from the application of this system to software-generated signals and utility sampled disturbance events.

Hearing in renal failure

The incidence of sensorineural hearing loss among patients with chronic renal failure (CRF) is considerably higher than in the general population. Bazzi et al. [1] found an incidence of 77% including patients with mild and very mild hearing loss. Ozturan and Lam [2] found a moderate to severe hearing loss in 46% of the tested patients. The general consensus in audiometric findings among patients with CRF claims a high frequency hearing loss [3,4] with a notch at 6 kHz [2]. Presence of hearing loss and estimation of type and degree constitute one of the most common methods used to investigate the effects of renal disease on the auditory system. Degree of hearing loss may give an indication of the extent of damage to auditory function, whereas the type of hearing loss may distinguish between lesions in the outer and middle ear (conductive hearing loss) or the cochlea and the neural pathways (sensorineural hearing loss). In addition to these indicators, the reports to be reviewed in the following sections have also described auditory function in CRF with methods such as otoacoustic emissions (OAEs) (namely transient evoked OAEs, TEOAEs and distorion product OAEs, DPOAEs), and auditory evoked potentials (AEPs). OAEs are low level sounds emitted by the cochlea in the process of receiving the sound vibrations and transforming them to cellular and neural stimulation. Recording of OAEs implies a functioning cochlea and healthy middle ear mechanism. TEOAEs are produced by the action of the hair cells, and they reflect special characteristics of the stimulus. DPOAEs are produced when the ear is stimulated with a combination of pure tones that are close in frequency (the primary tones). DPOAEs reflect non-linear processes of hair cell motion. Both TEOAEs and DPOAEs are generated by the active cochlear mechanisms responsible for enhancing basilar membrane vibration; this is known as the ‘cochlear amplifier’ [5]. AEPs represent neural activity related to auditory stimulation. They show summated neural energy at the various synaptic levels of the auditory pathway; this activity is generated by specific stimuli and extracted from the ongoing EEG activity by specialized technical manipulation. AEPs are recorded from the scalp representing activity in the cochlea and brainstem, thalamus and cortical areas. They are distinguished in early, middle and late evoked potentials, respectively. AEPs recorded from the cochlea include the cochlear microphonic (CM), the summating potential (SP) and the auditory nerve action potential (AP). The CM originates in the outer hair cells and mirrors the incoming signal. The SP also reflects hair cell function. The auditory nerve AP represents the sum of synchronous responses of auditory nerve fibers at the level of the cochlea. The largest component of the AP is the N1, a characteristic wave that constitutes also the first identifiable component of the auditory brainstem response (ABR). The ABR is also an ‘early’ evoked response, as it reflects neural function along the ascending auditory pathway, from the cochlea to the inferior colliculus. The five distinct waves of the normal ABR waveform are mainly generated by successive nuclei in the ascending auditory pathway: waves I and II originate from the distal and proximal portions of the auditory nerve, respectively, wave III originates from the cochlear nucleus, wave IV originates from the superior olivary complex and wave V originates from the lateral lemniscus/inferior colliculus. Each higher level order wave receives contributions from lower levels of the pathway [6]. The AEP reflecting function from auditory cortical areas is the Auditory Late Response (ALR). Major identifiable waves of the ALR are the N1 and P2 waves. ALR measurements reflect higher-level auditory function [7]. In general, latency of AEP waves indicates speed of neural function, whereas amplitude is a variable indicator of response robustness. The cochlea and kidney have similar physiological mechanisms, namely the active transport of fluid Correspondence and offprint requests to: Dr Chryssoula ThodiPetrou Cyprus, Audiology Center, Kallipoleos and 1Damaskinos Str, 1070, P.O. Box 20739, 1663 Nicosia, Cyprus. Email: DrC@cyprusaudiologycenter.com Nephrol Dial Transplant (2006) 21: 3023–3030

Tardus–parvus Doppler waveform in the renal arteries of an adult patient suggesting aortic coarctation

A 19-year-old man presented with arterial hypertension without blood pressure difference between his upper and lower extremities. Duplex Doppler sonography was performed to rule out renal artery stenosis and revealed a tardus-parvus pattern in both renal arteries as well as in the abdominal aorta, whereas the left subclavian artery showed a normal waveform, suggesting a more distal obstruction. Aortography confirmed a severe aortic coarctation. Because the typical signs and symptoms of aortic coarctation may not be present, especially in adults, a tardus-parvus pattern in the abdominal aorta and its branches, contrasting with a normal pattern in the supra-aortic arteries, should suggest the diagnosis.

Non-visualization of the internal carotid artery with a normal ipsilateral common carotid artery Doppler waveform: a finding suggesting congenital absence of the ICA on colour Doppler ultrasound

We report a case of congenital absence of the left internal carotid artery (ICA) that presented with left-sided facial numbness. On MRI of the brain, occlusion of the left cavernous ICA was suggested. On colour Doppler ultrasound (CDS), the left ICA was not visualized and the ipsilateral common carotid artery (CCA) showed normal flow in systole and diastole. Combined with the correct identification of the left external carotid artery (ECA), these findings were suggestive of congenital absence of the ICA rather than occlusion. The final diagnosis of congenital absence of the ICA was confirmed with CT of the skull base.

OP04.23: Impaired systolic and diastolic ventricular function after permanent extra‐embryonic venous obstruction, a pressure‐volume loop assessment in the stage‐24 chick embryo

Hydrops fetalis is the final common hemodynamic pathway for a variety of pathological states in the fetus, including high output states associated with fetal anemia or arterio-venous fistulas and abnormalities of both cardiac structure and rhythm. Hydrops fetalis secondary to cardiovascular decompensation is usually accompanied by elevations in fetal systemic venous pressure as evidenced by alterations in venous Doppler waveforms. We present two cases of severe fetal aortic stenosis with left ventricular fibroelastosis and mitral regurgitation and in utero closure or stenosis of the foramen ovale, with severe hydrops fetalis, despite normal systemic venous Doppler flow profiles. Both cases demonstrated markedly abnormal fetal pulmonary venous Doppler waveforms and after birth, both infants were hypoalbuminemic. The presence of normal systemic venous Doppler waveforms in fetuses with severe hydrops fetalis and structural cardiac disease challenges our understanding of the etiology of this pathological state. These cases have led us to reconsider the presumed etiology of cardiogenic hydrops fetalis in fetuses with severely impaired left ventricular pump function and secondary mitral regurgitation. We hypothesize that elevated pulmonary venous pressure, with only mildly increased central venous pressure, may negatively impact pulmonary lymphatic flow, decrease serum oncotic pressure due to loss of protein-rich fluid in the pulmonary interstitium, increase venous hydrostatic pressure, and lead to hydrops fetalis.

Guidelines for Noninvasive Vascular Laboratory Testing: A Report from the American Society of Echocardiography and the Society of Vascular Medicine and Biology

Accompanying the rapid growth of interest inpercutaneous vascular interventions, there hasbeen increasing interest among cardiologists inperforming noninvasive vascular testing using ul-trasound. In an attempt to provide recommenda-tions on the best practices in vascular laboratorytesting, this report has been prepared by a writinggroup from the American Society of Echocardiog-raphy (ASE) and the Society of Vascular Medicineand Biology. The document summarizes principlesintegral to vascular duplex ultrasound–includingcolor Doppler, spectral Doppler waveform analy-sis, power Doppler, and the use of contrast.Appropriate indications and interpretation of ca-rotid artery, renal artery, abdominal aorta, andperipheral artery ultrasound imaging are de-scribed. A dedicated section summarizes noninva-sive techniques for physiologic vascular testing ofthe lower extremity arteries–including measure-ment of segmental pressures and pulse volumeplethysmography. The use of exercise testing inthe evaluation of peripheral artery disease, ultra-sound evaluation of the lower extremities afterpercutaneous revascularization, and the diagnosisand management of iatrogenic pseudoaneurysm(PSA) is also discussed. A section on the importanttopic of vascular laboratory accreditation is in-cluded. Finally, additional details regarding propertechnique for performance of the various vasculartests and procedures are included in the Appen-dix.

Activated partial thromboplastin time waveform analysis: A new tool to detect infection?*

An abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time (aPTT) has been described to identify a high-risk intensive care unit population consisting of patients with sepsis or with higher mortality rates than patients with normal aPTT waveforms. We investigated the abnormal aPTT biphasic waveform as a diagnostic and prognostic marker of infection. Prospective, observational study investigating the predictive value of aPTT waveform analysis for the diagnosis and prognosis of sepsis. Surgical intensive care unit of a university hospital. We studied 187 consecutive patients who fulfilled at least two or more criteria of the systemic inflammatory response syndrome at admission or during intensive care stay and classified as having systemic inflammatory response syndrome, sepsis, severe sepsis, or septic shock during an 8-month period. Laboratory analyses including aPTT waveform analysis and procalcitonin and C-reactive protein concentrations were measured at days 1-3. The final diagnoses were systemic inflammatory response syndrome in 49%, sepsis in 16%, severe sepsis in 12%, and septic shock in 23% of patients. On day 1, the biphasic waveform was significantly more abnormal in patients with severe sepsis or septic shock than in patients with systemic inflammatory response syndrome or sepsis. The biphasic waveform was more accurate than procalcitonin and C-reactive protein for differentiating patients with severe sepsis and septic shock, with 90% sensitivity and 92% negative predictive value. Biphasic waveform values were significantly more abnormal during days 1-3 in septic nonsurvivors than in survivors and nonseptic nonsurvivors. The biphasic waveform exhibited the best specificity (91%) and negative predictive value (98%) for the prognosis of sepsis-related mortality on day 3. In intensive care units, when the analyzer is available, aPTT waveform analysis is an inexpensive, rapid, effective, and readily available tool providing information for the diagnosis of severe sepsis and the prognosis of septic patients.

ABC of wound healing: Diabetic foot ulcers

Diabetic foot ulcers can be divided into two groups: those in neuropathic feet (so called neuropathic ulcers) and those in feet with ischaemia often associated with neuro-pathy (so called neuroischaemic ulcers). The neuropathic foot is warm and well perfused with palpable pulses; sweating is diminished, and the skin may be dry and prone to fissuring. The neuroischaemic foot is a cool, pulseless foot; the skin is thin, shiny, and without hair. There is also atrophy of the subcutaneous tissue, and intermittent claudication and rest pain may be absent because of neuropathy. The crucial difference between the two types of feet is the absence or presence of ischaemia. The presence of ischaemia may be confirmed by a pressure index (ankle brachial pressure index <1). As many diabetic patients have medial arterial calcification, giving an artificially raised ankle systolic pressure, it is also important to examine the Doppler arterial waveform. The normal waveform is pulsatile with a positive forward flow in systole followed by a short reverse flow and a further forward flow in diastole, but in the presence of arterial narrowing the waveform shows a reduced forward flow and is described as “damped.” Neuropathic ulcers usually occur on the plantar aspect of the foot under the metatarsal heads or on the plantar aspects of the toes. The most common cause of ulceration is repetitive mechanical forces of gait, which lead to callus, the most important preulcerative lesion in the neuropathic foot. If allowed to become too thick, the callus will press on the soft tissues underneath and cause ulceration. A layer of whitish, macerated, moist tissue found under the surface of the callus indicates that the foot is close to ulceration, and urgent removal of the callus is necessary. If the callus is not removed, inflammatory autolysis and haematomas develop under …

Maternal serum concentration of soluble fms-like tyrosine kinase 1 and vascular endothelial growth factor in women with abnormal uterine artery Doppler and in those with fetal growth restriction

This study was undertaken to determine whether maternal serum concentration of the angiogenic factor vascular endothelial growth factor (VEGF) and its circulating antagonist, soluble fms-like tyrosine kinase 1 (sFlt-1), which have been implicated in the pathogenesis of preeclampsia (PE), are altered in pregnancies that subsequently develop PE and in those with established fetal growth restriction (FGR). Three groups of healthy pregnant women at 23 to 25 weeks of gestation were examined: group A (n = 42) with normal uterine artery Doppler waveforms, group B (n = 49) with abnormal uterine artery Doppler waveforms, and group C (n = 15) with abnormal Doppler results and established FGR. Comparisons between multiple groups were performed by using 1-way analysis of variance or Kruskal-Wallis test. In group C, compared with group A, the median sFlt-1 was significantly higher (P < .0001) and VEGF was lower (P < .001). Group C included 3 women who had PE develop. In group B, 19 women had a normal outcome, 13 had PE develop, and 17 had FGR develop. There were no significant differences in sFlt-1 levels between any of the subgroups of group B and group A. Maternal serum concentration of sFlt-1 in pregnancies with FGR is increased but this increase is not evident in pregnancies with impaired placentation that subsequently had either FGR or PE develop.

Comparison of perinatal outcome of growth-restricted fetuses with normal and abnormal umbilical artery Doppler waveforms

To evaluate the role of umbilical artery Doppler in growth- restricted fetuses. In a prospective observational study, 70 pregnant women with growth-restricted fetuses confirmed by ultrasound, were followed up with Doppler studies of the umbilical artery. The study group consisted of 35 women, where the Doppler waveform in the umbilical artery was compromised (either absent end diastolic flow [AEDF] or reversed end diastolic flow [REDF]). These were compared with an equal number of controls, where growth- restricted fetuses had normal doppler waveforms. Outcome measures were evaluated in both groups and analyzed. The periods of gestation at delivery were 27.2 +/- 3.5 weeks in group 1 and 37 +/- 3.3 weeks in-group II, respectively. Perinatal morbidity and mortality was significantly increased in the group with compromised umbilical artery blood group. Birth weight in group I was 742 +/- 126 grams and in group II was 1680 +/- 259 grams. This difference was statistically significant (P=0.0001). In comparison to AEDF, REDF fetuses had more morbidities. Perinatal mortality was also significantly increased in this group (P=0.001). Umbilical artery Doppler should be used in the management of growth-restricted fetuses. In those fetuses in normal Doppler, pregnancy can be prolonged. REDF is an indication for termination of pregnancy.

Doppler-Sonographie der Aa. uterinae und Schwangerschaftskomplikationen bei unselektionierten Schwangeren

Purpose: Pre-eclampsia and fetal growth restriction are two of the most common causes of maternal and fetal morbidity and mortality. A population of low-risk women was screened by uterine artery Doppler for diastolic notch. A good performance of this screening method could help to detect high-risk pregnancies at an early stage in order to increase the patient surveillance. Patients and methods: Between January and December 2002, uterine artery color Doppler was performed by one single researcher in 578 healthy pregnant women between 20 and 24 weeks of gestation in order to detect bilateral diastolic notches. A bilateral notch in at least three consecutive heart cycles was considered positive. Results (specificity, sensitivity, positive predictive value, negative predictive value) were calculated for pre-eclampsia, small-for-gestational-age infants and delivery before 37 weeks of gestation. Results: A bilateral notch was found in 36 (7%) of 490 women, who remained in the study. The risk of developing one of the examined diseases was significantly increased in the notch group. Doppler ultrasound showed high specificity and high negative predictive values for all of the three diseases. Conclusion: Doppler screening for bilateral notching helps to avoid unnecessary examinations of women with normal uterine artery waveforms. On the other hand, women with bilateral notching benefit from early increased surveillance.

882. Non-Viral Ocular Gene Transfer for Hereditary Retinal Degeneration

Top of pageAbstract The present study was undertaken to determine the efficacy of DNA nanotechnology as an effective therapeutic strategy for eye diseases; particularly those associated with loss-of-function mutations in the retina and retinal pigment epithelium (RPE). Since many hereditary blinding disorders have an onset from birth, we first evaluated a method of delivery to the newborn mouse eye. Subretinal injections of saline were delivered into one eye at post-natal day 2 (P2) and the contra-lateral eye was left uninjected to serve as a control. These mice were then left in normal cyclic light to develop into adults. At P21, retinal function was assessed with electroretinography (ERG) and ocular structure was examined with histology. Eyes injected at P2 demonstrated normal scotopic and photopic ERG waveforms and displayed a normal cellular organization and morphology, as compared to contra-lateral controls. As this route of delivery was safe, we then sought to determine whether this method could be used to deliver compacted DNA nanoparticles for gene transfer. The Rds+/|[minus]| mouse has only one functional copy of the photoreceptor specific gene Rds, and presents with a progressive retinal degeneration which causes perturbation of retinal function and structure, eventually leading to death of photoreceptors. Rds+/|[minus]| mice at P2 were injected with compacted nanoparticles of plasmid DNA carrying the wild-type Rds cDNA directed by the chicken b-actin promoter (Rds-particles), or the non-compacted naked plasmid (Rds-plasmid). Similar to experiments described above, one eye was injected, and the contra-lateral eye served as a non-injected control. At P30 and P45 these animals were subjected to ERG to assess photoreceptor viability. Eyes receiving Rds-nanoparticles showed an increased scotopic a- and b-wave, in addition to an increased photopic b-wave. However, eyes receiving naked Rds-plasmid failed to demonstrate an increase in ERG function at the timepoints examined. In contrast, Rds+/|[minus]| mice that received a subretinal delivery of Rds-nanoparticles at P21 failed to show any rescue of photoreceptor function when assessed by ERG at 7, 14, and 21 days post-injection. These studies demonstrate the feasibility of newborn treatment strategies for retinal degenerative disorders and provide a rationale for future therapeutic interventions. Further studies are underway to determine the longevity of rescue in animals treated at P2 and whether nanoparticle treatment resulted in amelioration of the structural abnormalities associated with the Rds+/|[minus]| retina.

Traumatic Intracranial Arteriovenous Malformation

Introduction This report is the first of a traumatic intracranial arteriovenous malformation (AVM) identified with the use of ultrasound imaging. This case study involves a 49-year-old man with a traumatic intracranial arteriovenous malformation that was identified using transcranial imaging and spectral analysis studies. Methods Transcranial ultrasonic imaging with spectral analysis was performed, using a 2.5MHz hand-held probe identified the traumatic AVM. Correlated follow-up testing was conducted using magnetic resonance angiography and computed tomography scan. Results were correlated with ultrasound findings. Results Bilateral middle cerebral and anterior cerebral arteries were identified revealing normal waveforms and velocities. Left posterior cerebral artery could not be insonated or visualized whereas the right posterior cerebral artery revealed normal waveforms and velocities. A single area of “jet” flow was in the distal internal carotid artery (in the area of carotid cavernous sinus). A peak systolic velocity of 318 cm/sec and an end diastolic velocity of 152 cm/sec were identified in the “jet,” which is consistent with the clinical suspicion of an AVM. The magnetic resonance angiography demonstrated normal right internal carotid, middle cerebral, and anterior cerebral arteries. On the left, there was diffusion of signal in the region of the cavernous sinus. This flow signal extended anteriorly and laterally into the region of the lateral orbit. Also, a second channel of flow appeared extending up into the middle cerebral artery territory, suggesting some retrograde venous flow. Findings reported were consistent with AVM of the carotid artery at the cavernous sinus. Conclusion This report represents with the first reported incidence of diagnosis of traumatic AVM of intracranial vessels. Duplex scanning should be considered if concern exists for such an entity as it appears capable of actually identifying this pathology.

Changes in Endothelial Function Precede the Clinical Disease in Women in Whom Preeclampsia Develops

Endothelial dysfunction is important in the pathophysiology of preeclampsia. No study has examined endothelial function sequentially at different gestations before development of the clinical syndrome and after delivery (to compare maternal from placental influences). We sought to determine whether endothelial function changes before the clinical development of preeclampsia. We measured skin microvascular function using iontophoresis of acetylcholine and sodium nitroprusside, and laser Doppler imaging at 22, 26, 34 weeks' gestation and 6 weeks postpartum in women identified as being at increased risk of preeclampsia, based on uterine artery Doppler waveforms at 18 to 20 weeks, and controls with normal Doppler waveforms. Fifty-four women remained normotensive and preeclampsia developed in 15. In normotensive and preeclamptic women, acetylcholine responses were augmented during pregnancy compared with postpartum responses (P<0.001). Sodium nitroprusside responses were augmented during pregnancy compared with those postpartum (P<0.005) in preeclamptic women only. Microvascular responses were augmented in women in whom preeclampsia developed, compared with those in normotensive women, at 26 and 34 weeks for acetylcholine (P<0.05 and P<0.001, respectively) and at 22 and 26 weeks for sodium nitroprusside (P<0.05 and P<0.02, respectively). Postpartum acetylcholine and sodium nitroprusside responses were not significantly different between preeclamptic and normal women. Microvascular responses are enhanced during pregnancy in women in whom preeclampsia develops to a level above that seen in normotensive women. These changes precede the onset of clinical disease and might be related to a compensatory increased sensitivity of the microcirculation to nitric oxide.

Use of uterine Doppler in an Australian level II maternity hospital

To evaluate the clinical usefulness of uterine Doppler. Retrospective study between March 2001 and March 2003. A high-risk population of pregnant women in a busy level II Maternity unit. Resistance index (RI) measurements of the right and left uterine artery were obtained by using pulsed wave Colour Doppler. The presence of a unilateral or bilateral early diastolic notch was noted. An abnormal result was defined as a mean RI >or= 0.58 with no, one or two notches or a mean RI < 0.58 in the presence of bilateral notches. Pre-eclampsia was found in 45 (24.7%) women, gestational hypertension (GH) in 22 (12.1%) and intrauterine growth restriction (IUGR) in 42 (23.1%) of women included (total 59.9%). In the overall group, 127 (69.8%) women were found to have abnormal uterine artery Doppler results and 55 (30.2%) of patients had a normal Doppler study. No significant differences were found between the group of women with abnormal uterine artery Doppler and the women with a normal velocity waveform in the prediction of pre-eclampsia, IUGR and GH, this was also true in the various high-risk-subgroups. Uterine Doppler is not particularly useful to the obstetrician in the management of patients with an a priori very high risk to develop uteroplacental insufficiency.

Correlation of shear stress with carotid plaque rupture using MRI and finite element analysis

Sirs: A 68-year-old man was referred to our specialist neurovascular clinic after suffering one episode of right carotid territory transient ischaemic attack two months previously when screening Doppler had revealed a more than 50 % right carotid stenosis (NASCET) [1]. He was a smoker but had no other vascular risk factors. Conventional intra-arterial angiography confirmed a 57 % right carotid stenosis (NASCET) with a small ulcer into the plaque (Fig. 1A). The patient underwent high-resolution (0.39 0.39 mm) multi-spectral axial MRI of the carotid arteries (Fig. 1B–E). Imaging was conducted on a 1.5T clinical machine with a dedicated surface phase-array coil wrapped around the neck. The MRI protocol is summarised as follows: ECGgated, blood-suppressed, fast spinecho pulse sequences: PDW (TR/TE: 2 RR/46), T2-weighted (TR/TE: 2 RR/100), STIR (TR/TE/TI: 2 RR/46/150), and T1weighted (TR/TE: 1 RR/7.8). This revealed a high-risk plaque with a large necrotic core and a thin fibrous cap which was ruptured at the shoulder region (Fig. 1B–E). The patient subsequently underwent carotid endarterectomy and the atheromatous plaque was excised intact and retrieved for ex vivo histological analysis. This confirmed a complex Type VI plaque (large lipid core with thin ruptured fibrous cap) according to the classification of the American Heart Association, closely corroborating the in vivo MRI findings (Fig. 1F) [2]. The patient remains asymptomatic to date and is maintained on a combination of aspirin and statin. We also retrospectively performed computational modelling of the stresses acting on the plaque [3]. 2-D vessel wall geometry and intra-plaque constituents were manually segmented based on the in vivo MRI and used as a basis for finite element analysis (FEA) (ABAQUS software V 6.4–1, Rhodes Island, Providence). Mechanical properties of the lipid core and fibrous cap were assigned according to literature-derived experimental values [4]. Maps of stress distribution (force per unit area) produced as a result of the normal intra-luminal blood pressure waveform were generated along the length of the plaque. Such a representative stress map is shown in Fig. 1F. Maximum von Mises shear stress (672.5 KPa) was observed at the shoulder region of the plaque, closely correlating with the site of rupture on both MRI and histology. In this particular case, the combination of angiographic ulceration and vulnerable morphological features on MRI suggested that the patient was at high risk of subsequent stroke and contributed to the decision to recommend carotid endarterectomy despite only a moderate degree of stenosis (57 %) being present [5, 6]. MRI is fast emerging as a robust tool for accurate plaque characterisation [7–9]. Limited multi-weighted slices through the plaque can be easily acquired at the same sitting as an MR angiography examination, adding approximately an additional 20 minutes to the examination. This may prove particularly important for individualized risk stratification in patients with moderate or asymptomatic stenosis, in whom the overall benefits of surgery and decision-making based on luminal stenosis alone are clearly less well defined [10, 11]. FEA is a computer-based numerical technique, used for modelling the strength and behaviour of complex engineering structures, which has been applied to the study of atherogenesis and stresses acting on the carotid arterial wall [12]. In the finite element method, a structure is broken down into many small simple elements and the equations describing the behaviours of the individual elements are joined into complex set of equations that describe the behaviour of the whole structure. MRI now provides an ideal in vivo geometric template with which to study the role of mechanical stress on plaque behaviour, in contrast to previous studies based mainly on ex vivo and in vitro experimental studies [13, 14]. In the case we describe, the close spatial correlation of maximum shear stress with the site of fibrous cap rupture provides supporting evidence that mechanical stress may indeed be an important contributor to plaque rupture [3]. The high magnitude of stress observed was directly related to the plaque composition and relative amounts and geometry of lipid and fibrous components. Larger scale prospective studies are, however, necessary to validate these preliminary imaging and quantitative findings in the clinical prediction of plaque rupture. LETTER TO THE EDITORS

Intraocular Properties of Hexadecyloxypropyl–Cyclic-Cidofovir in Guinea Pigs

We previously reported a long-lasting crystalline lipid pro-drug of cyclic cidofovir, hexadecyloxypropyl-cyclic-cidofovir (HDP-cCDV), to treat experimental retinitis in rabbit eyes. With HDP-cCDV there was a longer intraocular therapeutic effect than with cidofovir (CDV) and no toxicity with 100 microg/eye. It has been known that CDV and related analogues lower intraocular pressure (IOP) after local use, and it is also accepted that the guinea pig is a better model to study this toxicity before human clinical trials. HDP-cCDV was intravitreally injected into 10 guinea pig eyes in doses of 4, 9, and 18 microg in 20 microL/eye. An 18-microg quantity is the dose equivalent to 100 microg/eye in the rabbit. Only one eye of each animal received drug and the fellow eye served as the control. After injection, the eyes were monitored with tonometry, ophthalmoscopy, electroretinography (ERG), and histology. Intravitreal injections of doses of 18 microg/eye or lower revealed no toxicity and a high therapeutic index (132,000 to 3300 times higher than the 50% effective concentration for human cytomegalovirus) during 10 weeks of observation. The crystalline drug depot was ophthalmoscopically visible in the inferior vitreous cavity for 5-10 weeks. There was no difference in IOP between the drug-injected and control eyes at any time points (P > 0.05) except for day 3 after drug injection (P = 0.0338). All eyes demonstrated a normal ERG waveform with no differences between the treated and the fellow control eyes (P = 0.85). Histology revealed normal morphology and structures of the retina and ciliary body in all eyes (with or without treatment). Crystalline HDP-cCDV may be a long-lasting and safer alternative to cidofovir to treat CMV retinitis without the retinal or ciliary body toxicity observed with CDV.

Placental morphometry and Doppler flow velocimetry in cases of chronic human fetal hypoxia

Objective: To investigate the structural basis of abnormal Doppler waveforms in the utero-placental circulations in cases of chronic fetal hypoxia. Study design: Morphometric analysis was performed on placental samples from 58 pregnancies with abnormal Doppler waveforms in the uterine, placental and umbilical circulations at 32–34 weeks, and 10 pregnancies with normal waveforms. Results: The volume of placental villi reduced from 350.5 cm 3 in controls to 286.4 cm 3 ( P < 0.05) in the severest cases. The volume of the fetal capillaries reduced from 59.7 cm 3 to 20.5 cm 3 ( P < 0.05). These reductions were associated with increased placental infarction. The myometrial segments of the spiral arteries were severely constricted, demonstrating failure of physiological conversion secondary to deficient trophoblast invasion. Conclusion: The placental vascular bed is greatly reduced in cases of chronic fetal hypoxia. We propose impaired placental perfusion causes oxidative stress and regression of the fetal vasculature, leading to fetal growth retardation and distress.

Use of umbilical‐cerebral Doppler ratios in predicting fetal growth restriction in near‐term fetuses

To compare the sensitivity and specificity of different umbilical-cerebral ratios in the prediction and detection of fetal growth restriction in near-term fetuses when the umbilical arterial waveform is within normal. A prospective cross-sectional observational study was carried out recruiting consecutive singleton pregnancies with clinically suspected fetal growth restriction after 34 weeks gestation. The umbilical-cerebral ratios were then calculated from the S/D, RI and PI values and correlated with immediate perinatal outcome. A total of 187 patients were recruited. Twelve cases had abnormal UA Doppler flow velocity waveform studies. Of the 175 with normal UA Doppler findings, 92 (53.1%) were confirmed to have fetal growth restriction (FGR) with birth weights below the tenth centile for gestation. The detection rate of FGR by ultrasound biometry was 96.7%. The mean umbilical artery S/D, RI and PI values were higher in the fetal growth restriction group, while the middle cerebral artery values were lower as compared to fetuses with no growth restriction. A small but significant difference was seen in the umbilical-cerebral ratios of the different indices between the two groups. Receiver operator characteristic curves showed that there was little difference between the performances of the S/D, RI or PI ratios and all had limited power in predicting fetal growth restriction. In the presence of normal umbilical artery Doppler waveforms, umbilical-cerebral ratios have limited power to predict fetal growth restriction.

A Prospective Analysis of the Role of Uterine Artery Doppler Waveform Notching in the Assessment of At-Risk Pregnancies

Objective. To determine the value of second trimester uterine artery Doppler waveform notching in the prediction of adverse pregnancy outcome in a high-risk group. Design. Analysis of data from a consecutively collected cohort. Setting. St. James University Hospital, Leeds, UK. Population. Three hundred thirty women known to be at risk of preeclampsia (PET) or intrauterine growth restriction (IUGR) were assessed for notching of the uterine artery Doppler waveform between 24–30 weeks of pregnancy. Main Outcome Measures. Preeclampsia (PET), small-for-gestational-age at birth (SGA), preterm delivery (PTD), perinatal death. Results. Two hundred thirty-two women (70.3%) had a normal uterine artery Doppler waveforms, and 98 (29.7%) demonstrated either unilateral or bilateral notching. In women where notching was present, 20 (20%) developed PET compared with 8 (3.5%) in the normal group [Odds ratio (OR) 7.2, CI 3–17]; SGA birthweight was present in 24 (24.5%) of the notched group and in 21 (9%) of normal group (OR 3.3; CI 1.7–6.2); 40 (41%) of the notched group delivered preterm ( < 37 weeks) as compared with 37 (16%) of the normal group (OR 7.9; CI 4.6–13). This difference was even more marked when delivery before 32 weeks was considered, occurring in 8 (8%) of the notched group and 4 (1.7%) of the normal group (OR 11.5; CI 4.5–29.4). Of the six perinatal deaths, five (5.1%) occurred in the notched group (OR 12.4; CI 1.4–108). Conclusion. This study demonstrates that the addition of uterine Doppler waveform analysis to the monitoring profile of women at risk of PET, SGA, IUD and preterm delivery can further define those in a higher risk group and the majority that have a risk no higher than the background.