Persistent growth failure in Prader-Willi syndrome associated with short-chain acyl-CoA dehydrogenase gene variant

The authors report the rare association of Prader-Willi syndrome and short-chain acyl-CoA dehydrogenase gene variant. Prader-Willi syndrome, associated with paternal chromosome 15q11-q13 silencing, is characterized by neonatal/infantile hypotonia, growth failure, and neurodevelopmental delays in the first 1 to 2 years of life, typically followed by hyperphagia and obesity. Short-chain acyl-CoA dehydrogenase gene variant, with 625 G-to-A and 511 C-to-T changes, impairs C4-C6 fatty acid metabolism and variably causes neonatal/infantile hypotonia with developmental delays. The authors' patient continues to exhibit the classic severe growth failure of early infancy Prader-Willi syndrome at 40 months. Extensive laboratory investigations indicate that the short-chain acyl-CoA dehydrogenase gene variant is likely preventing or delaying the normal expression of the Prader-Willi syndrome phenotype.     

Utilization efficacy of noninvasive and invasive cardiac testing among stable cardiac patients undergoing noncardiac surgery.

BACKGROUND: Patients with coronary artery disease are at increased risk from noncardiac surgery. We examined a population of cardiac patients undergoing noncardiac surgery to determine whether coronary angiography was successfully utilized to identify and treat ischemic heart disease. Our hypothesis was that cardiac complications would not differ between the group of patients who underwent coronary angiography and the group that did not. METHODS: We conducted a secondary analysis from a prospective, cohort study of 314 patients with stable cardiac disease undergoing elective noncardiac surgery. The cohort was stratified by history of coronary arteriography. Follow-up extended postoperatively for a minimum of 30 days or until discharge if later. RESULTS: Of this cohort, 37.9% of the patients had a coronary angiogram at a median interval of 19 months (range, 1 day-13 years) before surgery. Among the 15 cardiac deaths (4.8%), 14 patients had compensated congestive heart failure and/or diabetes. The two arms were similar by surgical risk. Despite a higher clinical risk (P<.001), the catheterized vs. noncatheterized arm exhibited a similar cardiac morbidity and a lower cardiac mortality (0.8% vs. 7.2%, P=.01). The lower cardiac mortality persisted whether the patients were recently or remotely catheterized and whether revascularized or not. CONCLUSION: Coronary arteriography is associated with mortality risk-reduction among stable cardiac patients undergoing intermediate-to-high-risk noncardiac surgery, but is unwarranted for low-risk procedures. A higher risk linked to diabetes and congestive heart failure suggests underutilization of noninvasive testing and coronary arteriography among patients with these diagnoses and stable cardiac disease.     

A biomechanical and morphologic analysis of capsule formation around implanted piezoelectric wafer active sensors in rats treated with cyclooxygenase-2 inhibition

Biomedical sensors can yield new information about the microenvironment of soft tissues around the devices. In the current study, wound healing in response to the placement of piezoelectric wafer active sensors (PWAS) was compared between control animals and those fed a diet with a COX-2 inhibitor over 5 months. Animals fed the experimental diet had statistically less dampening of the PWAS wave form over the entire study period compared with those fed standard chow. This finding implied a less viscous wound exudate in animals that have COX-2 inhibition. Histologically, animals fed the COX-2-inhibited diet displayed delayed maturation of the wound-healing response. However, at 5 months there was little difference histologically between the 2 groups. The use of PWAS sensors provides a new tool for investigating the physical properties of wound healing around soft tissue implants.     

The use of biomedical sensors to monitor capsule formation around soft tissue implants

Piezoelectric sensors have been shown to respond reproducibly to changes in tissue mechanical properties surrounding an implant over a 4-month period. The vibrational amplitude at a frequency corresponding to the radial resonance shows a statistically significant change over time. The initial period of inflammation is marked by a significant reduction in amplitude, which is indicative of an increase in viscous dissipation of the tissue. As collagen displaces the cellular response, the amplitude continues to decrease. Finally, as the tissue matures, the capsule becomes stiffer, and the viscous dissipation lessens. These results are consistent with qualitative assessments of explanted capsules. Strain gauges encased in a monolithic block of silicone exhibited a greater degree of variability, yet show similar trends over time. The strain increases in the initial 4-week period and remains relatively steady over the following 4 weeks. Beyond 8 weeks, the gauges begin to extrude from the animal or suffer a loss of electrical continuity. Steps are being taken to improve the strain sensor longevity in the animals.     

Normokinesia adjacent to left ventricular aneurysm: a differential risk for sudden cardiac death.

BACKGROUND: Following myocardial infarction, the ejection fraction (EF) is an indiscriminate predictor of both non-sudden cardiac death (NSCD) and sudden cardiac death (SCD). However, development of a left ventricular aneurysm (LVA) confers independent risk only for SCD. Thus, we tested the hypothesis that mechanical factors, other than the global left ventricular performance, are causally related to SCD in the presence of LVA. METHODS: A secondary analysis was conducted from a longitudinal, prospective, long-term follow-up cohort study of 66 patients with LVA (diastolic eccentricity and systolic dyskinesia) diagnosed by ventriculography. The left ventricular contour was divided into five segments and contractility scores for the residual myocardium and the segments adjacent to the aneurysm were allocated along with assessment of the EF. A normal adjacent segment was considered present when at least one segment adjacent to the aneurysm exhibited normokinesia. Presence of ventricular tachycardia was documented by Holter recording. RESULTS: At a 5.2-year median follow-up, there were 12 NSCD and 8 SCD. The EF was lower among patients who died vs. survivors (31.5% vs. 39.7%, P=0.01). Patients with NSCD and SCD, exhibited similar EF but disparate residual contractility scores (3.0 vs. 4.1, P<0.004). Among cardiac deaths, a decreasing residual contractility score differentially predicted NSCD (odds ratio=17.06, P<0.03), while a normokinetic adjacent segment differentially predicted SCD (odds ratio=21, P<0.02). Albeit a predictor of both NSCD and SCD, ventricular tachycardia increased markedly the model significance (P<0.004) only when tested with a normokinetic adjacent segment vis-a'-vis SCD. CONCLUSIONS: In the presence of LVA, the contractility of the non-aneurysmal myocardium is a differential predictor of death from pump failure. In contrast, a normal segment adjacent to LVA constitutes an independent and discriminate predictor of SCD, possibly through an arrhythmic substrate linked to the motion discordance between the expanding aneurysm and a normokinetic adjacent myocardium.     

Electromechanical impedance sensor for in vivo monitoring the body reaction to implants.

A novel sensor for in situ monitoring of the body reaction to implants has been developed. A piezoelectric wafer active sensor was adapted for biomedical applications (bio-PWAS). A number of bio-PWAS sensors have been implanted in rats and left in place up to 64 days. The bio-PWAS were able to oscillate in several resonance modes, radial-wise (in-plane) and thickness-wise (out-of-plane). The electromechanical impedance was measured over a wide frequency band, covering several radial vibration modes and the first thickness mode. The recorded data was processed with impedance spectroscopy methods. Preliminary results indicate a correlation between the electromechanical impedance spectrum of the bio-PWAS and the state of implantation. Quantitative studies have shown that the first radial mode amplitude seems to correlate with the short-time inflammatory and immune response, while the thickness mode amplitude seems to correlate with both the short-term inflammatory response and long-term encapsulation and fibrosis response. Since radial vibrations generate shear waves in the surrounding tissue, while thickness vibrations generate pressure waves, it seems that the shear and pressure wave interactions have specificity in detecting the different stages of the body's reaction response to implants. These observations were supported by histological examinations of the tissue surrounding the bio-PWAS. Though these initial results are encouraging, further experiments need to be conducted and more data needs to be collected in correlation with histological determinations. In-depth impedance spectroscopy studies should be conducted on this extensive data and closely correlated with extensive histological studies.     

Electromechanical Impedance Sensor for In Vivo Monitoring the Body Reaction to Implants

A novel sensor for in situ monitoring of the body reaction to implants has been developed. A piezoelectric wafer active sensor was adapted for biomedical applications (bio-PWAS). A number of bio-PWAS sensors have been implanted in rats and left in place up to 64 days. The bio-PWAS were able to oscillate in several resonance modes, radial-wise (in-plane) and thickness-wise (out-of-plane). The electromechanical impedance was measured over a wide frequency band, covering several radial vibration modes and the first thickness mode. The recorded data was processed with impedance spectroscopy methods. Preliminary results indicate a correlation between the electromechanical impedance spectrum of the bio-PWAS and the state of implantation. Quantitative studies have shown that the first radial mode amplitude seems to correlate with the short-time inflammatory and immune response, while the thickness mode amplitude seems to correlate with both the short-term inflammatory response and long-term encapsulation and fibrosis response. Since radial vibrations generate shear waves in the surrounding tissue, while thickness vibrations generate pressure waves, it seems that the shear and pressure wave interactions have specificity in detecting the different stages of the body's reaction response to implants. These observations were supported by histological examinations of the tissue surrounding the bio-PWAS. Though these initial results are encouraging, further experiments need to be conducted and more data needs to be collected in correlation with histological determinations. In-depth impedance spectroscopy studies should be conducted on this extensive data and closely correlated with extensive histological studies.