Fracture of ceramic/ceramic/polymer trilayers for biomechanical applications

Fracture damage in trilayers consisting of outer and inner brittle layers bonded to a compliant (polycarbonate) substrate and subjected to concentrated surface loading is analyzed. The principal mode of fracture is radial cracking at the undersurface of the inner (core) layer, even in the strongest of core ceramics--other damage modes, including radial cracking in the outer (veneer) layer, are less invasive in these all-brittle coating systems. Tests on simple trilayer structures fabricated from glasses, sapphire, and dental ceramics are used to examine the dependence of the critical load for radial fracture in terms of relative outer/inner layer thickness and modulus, and inner layer strength. An explicit relation for the critical load, based on a flexing plate model in which the outer/inner bilayer is reduced to an "equivalent" monolithic coating with "effective" composite modulus, is used to examine these dependencies. The theoretical relation describes all the major trends in the critical load data over a broad range of variables, thus providing a sound basis for trilayer design. Relevance of the analysis to dental crowns and other biomechanical applications is a central theme of the study.     

Case-control study of cleft lip or palate after maternal use of topical corticosteroids during pregnancy

A case-control survey of 48 children with nonsyndromic cleft lip or palate showed a significant increase in prevalence of maternal use of topical corticosteroid preparations in the first trimester of pregnancy, compared to 58 controls born in the same hospital; the odds ratio was 13.154, 95% confidence interval 1.67-586, P = 0.0049 on Fisher's exact two-tail test. The results were statistically significant although the wide confidence interval reflected the small sample size. Although older epidemiological studies have not detected any association between systemic corticosteroid treatment and the combined incidence of all congenital malformations, experimental studies over several decades have shown that maternal corticosteroid exposure in several species of animals is specifically associated with oral clefts. This association has been confirmed by more specific case-control surveys where the cases were children with cleft lip or palate and the exposure was maternal systemic corticosteroid treatment in the first trimester. Only one previous survey also analyzed topical corticosteroids, and it demonstrated an increased odds ratio for cleft lip or palate. A national survey of children with cleft palate will be necessary to evaluate the results of this pilot study.     

Detection of high-risk atherosclerotic coronary plaques by intravascular spectroscopy

Multiple technologies are under development to identify plaque composition and vulnerability. This review article is intended to provide basic knowledge to the interventional cardiologist and the clinician about spectroscopy. The concept of light, the wavelength unit and the electromagnetic spectrum are discussed. Different types of spectra analysis including nuclear magnetic resonance, Raman, fluorescence and diffuse reflectance near-infrared spectroscopy are then carefully reviewed. Experimental data to identify atherosclerotic plaque composition for each of these techniques is provided. Potential benefits and challenges are addressed. Finally, diffuse reflectance near-infrared spectroscopy is discussed in more detail as a promising technique to characterize plaque vulnerability in humans.     

Evolution and cost trends of antihypertensive and hypolipidaemic drug treatment in France

Purpose: To assess the trends of the cost of cardiovascular disease prevention in France for period 1986–1997. Methods: MONICA population surveys conducted in two French Regions (Northern and Southwestern France). The individual costs of antihypertensive and hypolipidæmic drug treatment were established in 4765 subjects for the first (1985–1989) and the last (1995–1997) survey taking into account inflation rates and different daily posologies. Results: After correcting for inflation, minimum and maximum daily cost of antihypertensive treatment remained stable or decreased in both genders. Minimum daily cost for hypolipidæmic drugs remained stable but maximum costs increased considerably in both genders. This was further aggravated by a doubling of the number of subjects under hypolipidæmic drug treatment between both surveys. Conclusions: Individual daily cost of antihypertensive treatment has decreased whereas cost of hypolipidæmic treatment has increased during period 1985–1997. The higher number of subjects on hypolipidæmic drug therapy further increased the national expenditure for this class of drugs.     

Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome

Sudden unexplained nocturnal death syndrome (SUNDS), a disorder found in southeast Asia, is characterized by an abnormal electrocardiogram with ST-segment elevation in leads V1-V3 and sudden death due to ventricular fibrillation, identical to that seen in Brugada syndrome. We screened patients with SUNDS for mutations in SCN5A, the gene known to cause Brugada syndrome, as well as genes encoding ion channels associated with the long-QT syndrome. Ten families were enrolled, and screened for mutations using single-strand DNA conformation polymorphism analysis, denaturing high-performance liquid chromatography and DNA sequencing. Mutations were identified in SCN5A in three families. One mutation, R367H, lies in the first P segment of the pore-lining region between the DIS5 and DIS6 transmembrane segments of SCN5A. A second mutation, A735V, lies in the first transmembrane segment of domain II (DIIS1) close to the first extracellular loop between DIIS1 and DIIS2, whereas the third mutation, R1192Q, lies in domain III. Analysis of these mutations in Xenopus oocytes showed that the R367H mutant channel did not express any current and the likely effect of this mutation is to depress peak current due to the loss of one functional allele. The A735V mutant expressed currents with steady state activation voltage shifted to more positive potentials. The R1192Q mutation accelerated the inactivation of the sodium channel current. Both mutations resulted in reduced sodium channel current (I(Na)) at a time corresponding to the end of phase 1 of the action potential, as described previously in the Brugada syndrome. Based upon these observations we suggest that SUNDS and Brugada syndrome are phenotypically, genetically and functionally the same disorder.     

Magnetic resonance imaging of congenital,inflammatory, and infectious soft-tissue lesions in children

Magnetic resonance imaging has the advantages of multiplanar capability and high degree of tissue differentiation. It is useful for assessing the extent of soft-tissue abnormalities, such as vascular malformations, inflammatory and infectious processes, muscle disorders, and limb hypertrophy. Magnetic resonance imaging is sensitive to the presence of water and edema and is a good indicator for early diagnosis of inflammation and its level of activity. Fat-saturation techniques, including T2-weighted sequences and inversion recovery imaging, optimize diagnostic accuracy. T1-weighted images are good at defining the distribution and proportion of fat in the body, so they are useful in evaluating syndromes of the limbs, including vascular malformations, as well as lipoatrophy-lipodystrophy conditions. Magnetic resonance imaging provides guidance for efficient tissue biopsy. It allows comprehensive pretherapeutic assessment of soft-tissue vascular anomalies. It constitutes a good modality for following up the natural history of soft-tissue disorders during childhood.     

Toxic epidermal necrolysis associated with interleukin-2

BACKGROUND: Metastatic renal cell carcinoma (MRCC) has been characteristically unresponsive to chemotherapy. In lieu of an effective regimen, interleukin-2 (IL-2) and interferon alfa are considered drugs of choice to treat this cancer. Subcutaneous IL-2 is safe and well tolerated, with a mortality rate <3%. OBJECTIVE: To report a case of cutaneous and hematologic toxicity in a patient treated with IL-2. CASE SUMMARY: A 67-year-old woman received radiotherapy and immunotherapy for cancer that had metastasized to the bone and lungs. IL-2 was part of the regimen. After 5 days of treatment with IL-2, the patient developed a hemorrhagic lesion that progressed to toxic epidermal necrolysis, as well as grade 4 pancytopenia. She died 10 days after treatment was begun. At the time of death, leukocytes were 0.3 x 10(3)/mm(3), platelets 10 x 10(3)/mm(3), and hemoglobin 6.8 mg/dL. DISCUSSION: Cutaneous IL-2 adverse effects are frequent, but generally mild and reversible. The adverse hematologic effects are usually transitory and pancytopenia is not frequent. The severity of cutaneous and hematologic toxicity experienced by our patient has rarely been reported. CONCLUSIONS: The use of IL-2 in bedridden patients with performance status >2 must be given on an individualized basis. If radiotherapy over extensive areas of the body is needed, the use of IL-2 must be postponed until radiotherapy is completed.