Tele-echocardiography in paediatrics

Echocardiographic images can be transmitted over increasing distances with less cost and better quality thanks to advances in the field of telecommunications. This technological support can be used to detect heart defects in newborns and children in remote situations. The intent of this study was to confirm the feasibility and usefulness of telemedical communication for echocardiographic evaluation of paediatric cardiovascular disease. A total of 214 echocardiographs were performed in 194 children at a remote hospital by an experienced sonographer in paediatric echocardiography. These echocardiograms were transmitted to a distant tertiary care paediatric cardiology centre using a telemedicine link across three ISDN lines. There an experienced paediatric cardiologist interpreted the tele-echocardiograms. Tele-distant diagnoses were prospectively documented and compared with the diagnoses made subsequently on direct consultation and echocardiography. The quality of transmitted echocardiographic images was sufficient for evaluation except for one case. In 191 children (98%), the remote echocardiographic diagnosis was correct as confirmed by follow-up face to face consultations. Three cases were diagnosed incorrectly. CONCLUSION: our results confirm that accurate and rapid diagnosis can be provided by tele-echocardiography in neonates and children. This facilitates the appropriate care of these patients as expensive and potentially dangerous long-distance transfers can be avoided.     

Conformational-relaxation models of single-enzyme kinetics

Fluorescent spectroscopy experiments with single-enzyme molecules yield a large volume of statistical data that can be analyzed and interpreted using stochastic models of enzyme action. Here, we present two models, each based on the mechanism that an enzyme molecule must pass through a sequence of conformational transformations to complete its catalytic turnover cycle. In the simplest model, only one path leading to the release of product is present. In contrast to this, two different catalytic paths are possible in the second considered model. If a cycle is started from an active state, immediately after the previous product release, it follows a different conformational route and is much shorter. Our numerical investigations show that both models generate non-Markovian molecular statistics. However, their memory landscapes and distributions of cycle times are significantly different. The memory landscape of the double-path model bears strong similarity to the recent experimental data for horseradish peroxidase.     

Choroidal blood flow during exercise-induced changes in the ocular perfusion pressure

PURPOSE: The high metabolic rate of the human retina is supported by the choroidal vasculature. Knowledge of the normal choroidal blood flow (ChBF) responses to various physiological stimuli is therefore highly important if the pathophysiology of ocular diseases involving the choroid is to be understood better. In the present study, the hemodynamic responses of the subfoveal ChBF were examined during and after an exercise-induced increase in the ocular perfusion pressure (OPP). METHODS: Twenty-six healthy volunteers, 19 to 55 years of age participated in this two-phase study. Each subject increased resting OPP through stationary biking at a heart rate (HR) of 140 beats per minute (bpm) over 20 minutes. The ChBF was measured by laser Doppler flowmetry (LDF), the systemic BP by electronic sphygmomanometry, and the resting intraocular pressure (IOP) by applanation tonometry. RESULTS: The OPP increased by approximately 43% at the onset of biking, and then decreased biphasically to approximately 12% above resting value by the end of biking. The ChBF remained within 10% of its basal value throughout biking. Immediately after biking, the OPP decreased twice as much as the ChBF in the same time frame. CONCLUSIONS: The dissociation between the OPP and the ChBF during biking and recovery suggests that some mechanism keeps the ChBF close to its basal value, an observation that indicates blood flow regulation.     

Differential effects of vascular endothelial growth factor A isoforms in a mouse brain metastasis model of human melanoma

We reported previously that vascular endothelial growth factor isoform A (VEGF-A) expression by Mel57 human melanoma cells led to tumor progression in a murine brain metastasis model in an angiogenesis-independent fashion by dilation of co-opted, pre-existing vessels and concomitant enhanced blood supply (B. Kusters et al., Cancer Res., 62: 341-345, 2002). Here, we compare the activities of the 121, 165, and 189 VEGF-A isoforms in this model by transfecting Mel57 cells with the respective cDNAs and by injecting the resulting stably transfected cell lines in the internal carotid arteries of nude mice (n = 10 for each isoform). Although the three isoforms had similar potency to induce endothelial cell proliferation, VEGF(121) expression did not result in sprouting angiogenesis but rather led to extensive vasodilation and increased permeability of pre-existing, predominantly peritumoral vessels. Sometimes, proliferating endothelial cells accumulated in vessel lumina, giving these a microvascular, glomeruloid, proliferation-like appearance. Expression of VEGF(165) or VEGF(189) was associated with induction of an intratumoral neovascular bed. In VEGF(165)-expressing tumors, daughter endothelial cells were distributed among newly formed vessels that were extensively dilated. This also occurred in VEGF(189) tumors, but there, vasodilation was less pronounced. Using contrast-enhanced magnetic resonance imaging, the different vascular phenotypes were visualized on characteristic radiological images. VEGF(165) expression was the most unfavorable of the three. Mice carrying VEGF(165) tumors became moribund earlier than those carrying VEGF(121)-expressing tumors (16 +/- 4 days versus 22 +/- 3 days). Our data demonstrate that VEGF-A isoforms differ in angiogenic properties that can be visualized by contrast-enhanced magnetic resonance imaging.     

Kinematic changes after fusion and total replacement of the ankle: part 3: Talar movement

INTRODUCTION: The purpose of this study was to determine talar movement (e.g., talar rotation and talar shift during (dorsiflexion/plantarflexion) with respect to the tibia in the normal ankle, in the fused ankle, and in the replaced ankle by currently used prosthetic designs. METHODS: A 6-df device with an axial load of 200 N and a four-camera high-speed video system were used for the measurement of the range of motion in six fresh-frozen cadaveri leg specimens. While moving the foot through the whole range of motion for plantarflexion/dorsiflexion, segmental motion of the marked bones of the foot and shank were measured dynamically. Rotation and medial-lateral shift of the talus were then calculated with regard to flexion position of the foot. RESULTS: In the normal ankle, plantarflexion movement was coupled with talar inversion of 3.5 degrees, and dorsiflexion movement with talar eversion of 1.0 degree, in totally accounting for 4.5 degrees of talar rotation. While both the HINTEGRA and the S.T.A.R. prostheses did not show changes to the normal condition during the dorsiflexion/plantarflexion cycle (p < .05), talar rotation had a 60% decrease (p < .05) for the AGILITY prosthesis. In the normal ankle joint, a lateral talar shift of 1.4 mm was found to occur during dorsiflexion, and a lateral talar shift of 5.2 mm during plantarflexion. In both, the HINTEGRA and S.T.A.R. ankles, talar shift was converted into medial direction during dorsiflexion of the foot (difference to normal: p < .05), whereas talar shift in the lateral direction was found to occur during plantarflexion of the foot which was comparable to the normal ankle. The AGILITY ankle evidenced an 80% decrease of talar shift (p < .05) during the whole dorsiflexion/plantarflexion cycle. DISCUSSION: The two-component ankle (AGILITY) obviously tends to restrict tremendously talar motion within the ankle mortise, whereas the three-component ankles (HINTEGRA, S.T.A.R.) seem to allow talar range of motion comparable to that in the normal ankle. It is suggested that such a restriction of talar motion results in an increase of stress forces within and around the prosthesis, leading to polyethylene wear and potential loosening at the bone-implant interfaces. Therefore, a successful prosthetic design for the ankle should consist of three components that are shaped as anatomically as possible to provide a normal range of motion and to allow the full transmission of movement transfer between foot and shank and unconstrained movement of the talus within the ankle mortise.     

Awareness: Monitoring versus Remembering What Happened

Background: Awareness during anesthesia is foremost assessed with postoperative interviews, which may underestimate its incidence. On-line monitors such as the Bispectral Index(R) and patient response to verbal command are not necessarily commonly used. This study investigated response to command during deep sedation (Bispectral Index 60-70) and the ability of prevailing monitoring techniques to indicate awareness and predict recall.

Methods: The authors systematically assessed the response to command using the isolated forearm technique while monitoring electroencephalographic and hemodynamic variables. Fifty-six elective surgical patients were repeatedly given verbal instructions to squeeze the observer's hand during target-controlled infusion with propofol and alfentanil. After recovery, conscious recall was assessed with a short structured interview.

Results: Overall, 1,082 commands were given. No response was observed to 887 (82%) commands, an equivocal response was observed to 56 (5%) commands, and an unequivocal response was observed to 139 (13%) commands. Of the 37 patients (66%) with an unequivocal response to command ("awareness"), nine (25%) reported conscious recall after recovery. Their reports provided valuable insights as to how awareness may be adequately addressed. Hemodynamic variables poorly predicted awareness, whereas parameters derived from the encephalogram, especially the Bispectral Index, were highly significant predictors (P < 0.0001). Electroencephalographic parameters did not discriminate between patients with or without conscious recall, whereas heart rate and responsiveness to command did.     

Measurement of eye length and eye shape by optical low coherence reflectometry

Background: The precise and rapid measurement ofeye length and eye shape isessential for investigating eye growth regulation andmyopia. For this purpose, we developedan optical low coherence reflectometer (OLCR) andpresent preliminary measurements.Methods: The OLCR includes a super luminescentdiode (wavelength: 845 nm,coherence length: 30 m) and rotatingglass cube to produce longitudinal scansat a velocity of 0.42 m/s and a repetition rateof 13 scans/s. Heterodyne detection oflight reflected from the anterior cornea andthe posterior retina permits to measure axial eyelength and eye shape (off-axis eye length).Each measurement consists of five consecutivescans. Reproducibility and precision weredetermined in one volunteer by measuring axialeye length five consecutive times, each timerepositioning the eye. Eye shapes weredetermined in right eyes of four volunteers bymeasuring eye length every 3.3° from10° nasally to 10° temporally.Results: Axial eye length measured repeatedlyin one volunteer did not differ between orwithin the measurements (one-factor ANOVA). Theaverage standard deviation was11 m. Eye shapes (a) varied substantiallyamong subjects and (b) differed considerablyfrom the corresponding shapes of sphericalmodel eyes with identical axial eye lengths.Conclusion: The newly developed OLCRpermits the precise and rapid measurement ofeye length and eye shape. Such measurements,especially in children, may provide importantinformation about mechanisms of eye growthregulation and the development of myopia.     

A randomized comparison of the value of additional stenting after optimal balloon angioplasty for long coronary lesions: final results of the additional value of NIR stents for treatment of long coronary lesions (ADVANCE) study

OBJECTIVES: We sought to investigate the clinical benefit of additional stent implantation after achieving an optimal result of balloon angioplasty (BA) in long coronary lesions (>20 mm). BACKGROUND: Long coronary lesions are associated with increased early complications and late restenosis after BA. Stenting improves the early outcome, but stent restenosis is also related to both lesion length and stent length. METHODS: A total of 437 patients with a single native lesion 20 to 50 mm in length were included and underwent BA, using long balloons matched to lesion length and vessel diameter (balloon/artery ratio 1.1) to achieve a diameter stenosis (DS) <30% by on-line quantitative coronary angiography (QCA). "Bail-out stenting" was performed for flow-limiting dissections or >50% DS. Patients in whom an optimal BA result was achieved were randomized to additional stenting (using NIR stents) or no stenting. The primary end point was freedom from major adverse cardiac events (MACE) at nine months, and core laboratory QCA was performed on serial angiograms. RESULTS: Bailout stenting was necessary in 149 patients (34%) and was associated with a significantly increased risk of peri-procedural infarction (p < 0.02). Among the 288 randomized patients, the mean lesion length was 27+/-9 mm, and the vessel diameter was 2.78+/-0.52 mm. The procedural success rate was 90% for the 143 patients assigned to BA alone (control group), as compared with 93% in the 145 patients assigned to additional stenting (stent group), which resulted in a superior early minimal lumen diameter (0.54 mm, p < 0.001) and led to reduced angiographic restenosis (27% vs. 42%, p = 0.022). Freedom from MACE at nine months was 77% in both groups. CONCLUSIONS: A strategy of provisional stenting for long coronary lesions led to bailout stenting in one-third of patients, with a threefold increase in peri-procedural infarction. Additional stenting yielded a lower angiographic restenosis rate, but no reduction in MACE at nine months.     

Use of calcimimetics in uremic patients with secondary hyperparathyroidism: review

Recognition of the role of the extracellular calcium sensing receptor (CaR) in mineral metabolism has greatly improved our understanding of calcium homeostasis. The activation of this receptor by small changes in extracellular ionized calcium (ec(Ca2+)) regulates PTH, calcitonin secretion, urinary calcium excretion, and ultimately, bone turnover. The cloning of this CaR and the discovery of mutations making the receptor less or more sensitive to calcium allowed a better understanding of several hereditary disorders characterized either by hyperparathyroidism or hypoparathyroidism. This CaR became an ideal target for the development of compounds, the calcimimetics, able to amplify the sensitivity of the CaR to ec(Ca2+) suppressing PTH levels with a resultant fall in blood Ca2+. The first clinical studies with first-generation calcimimetic agents have demonstrated their efficacy lowering plasma intact PTH concentration in uremic patients with secondary hyperparathyroidism. However, the low bioavailability of these first calcimimetics predicts a difficult clinical utilization. The second-generation calcimimetic AMG-073, with a better pharmacokinetic profile, appears to be effective and safe for the treatment of secondary hyperparathyroidism, producing suppression of PTH levels with a simultaneous reduction in serum phosphorus levels and the calcium X phosphorus product. The advantage of controlling PTH secretion without the complications related to hypercalcemia, hyperphosphatemia, and increased calcium X phosphorus product is very promising.