Biomedical assessment and instrumental evaluation of healthy infant skin

The skin forms a critical structural boundary and a perceptual interface for the organism, yet the definition "healthy skin" is surprisingly difficult to describe. The present study's goal was to generate a technical definition of healthy infant skin by quantifying specific biophysical parameters before and after bathing in infants and correlating such parameters to a perceptual maternal evaluation. Fifty-two healthy infants, 3-6 months old, were evaluated before and after freshwater bathing. Diapered skin had a higher transepidermal water loss (TEWL), surface hydration, moisture accumulation rate (MAT), and friction than nondiapered skin before the bath (p < 0.01). Bathing dramatically altered the biophysical properties at both skin sites, with decreased MAT and lower friction, indicating a drier skin surface (p < 0.01). Visual redness and dryness decreased after bathing (p < 0.01). Blinded grading of optical images showed a significant preference for the skin after bathing (p < 0.01). This study provides the first quantitative technical definition of healthy infant skin with positive correlation to perceptual assessment by independent observers (mothers). The findings support the hypothesis that water binding properties of the stratum corneum are altered by occlusion (diapering) and that bathing introduces acute changes in stratum corneum water interactions, leading to a drier skin surface and a preferred skin appearance.     

Hepatitis C virus envelope glycoproteins and potential for vaccine development

HCV envelope glycoproteins play an important role in the initiation of viral infection. The functional dichotomy of the individual HCV glycoproteins was investigated using VSV/HCV pseudotype virus. Surprisingly, VSV/HCV pseudotype virus generated from either E1 or E2 displayed infectivity of a number of mammalian cells. The use of pseudotyped virus has allowed us to better understand the similar and divergent properties of E1 and E2 glycoproteins decorating the envelope of HCV. The serum pseudotype virus neutralizing activity in patient sera did not exhibit a correlation with the infecting HCV genotype or virus load. HCV E2 glycoprotein induces a weak neutralizing antibody response, however the neutralization function was augmented by complement. Taken together, these observations suggest a role for both the glycoproteins in HCV attachment and entry into susceptible host cells. An understanding of HCV entry and strategies appropriate for mimicking cell surface molecules may help in the development of new therapeutic modalities against HCV infection. Furthermore, incorporation of the HCV glycoproteins in a candidate vaccine may offer protection, although additional work is necessary to enhance their immunogenicity.     

Ventricular septal defect complicated by infective endocarditis of the aortic valve causing severe aortic regurgitation: the role of aortic valve repair

BACKGROUND AND AIMS OF THE STUDY: Children with ventricular septal defect (VSD) who develop severe aortic regurgitation following infective endocarditis (IE) require aortic valve replacement in most cases. Few reports exist of repair of the aortic valve under such circumstances. Here, we report details from two patients in whom aortic valve repair resulted in a good outcome. METHODS: Two children (aged 4 and 3 years) with either perimembranous or doubly committed subarterial VSD presented with congestive cardiac failure (NYHA class IV) following IE. The aortic valve in both children, and the pulmonary valve in one child, were severely damaged with vegetation, leading to severe (grade IV) aortic regurgitation. The second patient had bilateral bronchiectasis with respiratory infection and severe anemia. In addition to VSD closure, partial cuspal replacement using glutaraldehyde-tanned pericardium was performed successfully in both cases to restore geometry. RESULTS: Both children showed a dramatic improvement following surgery and during follow up of 36 and 11 months, respectively. Both remained asymptomatic, with good growth, good left ventricular function and the presence of only trivial aortic regurgitation. CONCLUSION: In selected patients with suitable anatomy, repair of the aortic valve with pericardial cusp replacement may be the procedure of choice. An additional benefit is the avoidance of long-term anticoagulation.     

Functional Role of Dendritic Cells in Patients with Unstable Angina

StudiesduringthelastdecadeidentifiedDCinatheroscleroticplaques.Dendriticcellsarepresentintheirimmatureformsinthearterialwallandareactivatedduringatherogenesis[1,2],whichprovidesanewapproachtoexplorethemechanismofT cellactivation[3].Dendriticcellsarefoundinaorticatheroscleroticlesionsinratswithdiet inducedhy percholesterolemia[4]andalsoinapolipoproteinE deficientmice[5].Dendriticcells(DC)wereoriginallydescribedbySteinmanandCohnin1973.Theyarethekeyantigen presentingcellsandarebelievedtoplaya…     

Eradication of spontaneous and experimental adenocarcinoma metastases with chronic indomethacin and intermittent IL-2 therapy

We had earlier shown that tumor-bearing results in an inactivation of IL-2–dependent effector cells by host macrophagederived PGE₂, and that chronic indomethacin therapy (CIT) aimed at blocking prostaglandin synthesis, combined with multiple rounds of IL-2, can cure experimental metastases of a variety of tumors in mice. We have now tested the efficacy of this therapy on spontaneous as well as experimental metastasis of C3–L5 mammary adenocarcinoma in C3H/HeJ mice. Mice transplanted s.c. with C3–L5 cells (and showing visible spontaneous lung metastases between days 7 and 10) were given CIT starting on day 15, plus 2 5–day rounds of IL-2 or IL-2 alone. Mice injected i.v. with 10⁴ C3–L5 cells (and showing lung micrometas-tases on day 5) were placed on CIT on day 5 and given 3 5–day rounds of IL-2 or treated with IL-2 alone. Control mice received vehicles alone. Results revealed that combined CIT + IL-2 therapy in the spontaneous metastasis model caused a regression of primary tumors, a marked reduction in lung metastases scored on days 25–35 and a marked prolongation of host survival (79% cured). Survivors rechallenged with 10⁴ tumor cells i.v. on day 210 resisted tumor growth. In the experimental metastasis model, this therapy also markedly reduced lung metastases and prolonged animal survival (50% cured). In both models, the combination therapy led to the presence of highly active tumoricidal (for C3–L5 and YAC-I lymphoma targets) lymphocytes with AGM-I⁺, Lyt-2^- and Thy-l± phenotype and macrophages in the spleen and the lungs, and ADCC-promoting activity in the serum. CIT + IL-2 therapy can thus effectively eradicate spontaneous and experimental mammary adenocarcinoma metastasis in mice. It activates natural effector cells in situ, generates ADCC-promoting activity in the serum and results in resistance to umor take in this moderately immunogenic tumor model.     

Cardiolipin-fluorescent (M1) antimitochondrial antibody and cholestatic hepatitis in secondary syphilis

Summary A 27-year-old black male with secondary syphilis and cholestatic jaundice is presented. The liver biopsy was believed to be most consistent with large bile duct obstruction, but both the ultrasound and endoscopic retrograde cholangiography were normal. Prior to treatment with penicillin, his serum was positive for antimitochondrial antibody. After treatment, the antibody was no longer detectable and the jaundice gradually resolved. The patient's pretreatment serum was, after further analysis, found to be positive for the antibody to the M1 antimitochondrial antigen subtype, which is identical to cardiolipin, the antigen in both the VDRL and Wasserman tests. A review of hepatic involvement in secondary syphilis is presented.     

Analysis of spatial correlation between 99mTc-Sestamibi uptake and radiographic breast density

Breast scintigraphy is a technique by which the biological properties of breast lesions can be assessed using an injected radiopharmaceutical. It may be particularly useful for women with radiographically dense breasts, in whose mammograms, lesions are often obscured by breast tissue. We are evaluating a dual modality breast scanner developed at the University of Virginia for its ability to distinguish between benign and malignant lesions. The scanner obtains a digital mammogram and a gamma ray emission image in quick succession with the breast held under mild compression, resulting in a fused image in which structures in the digital mammogram can be directly correlated with those in the scintigram. Our experience has shown that radiopharmaceutical uptake by normal breast tissue can sometimes obscure uptake by small lesions. It would therefore be advantageous to correct for this background uptake if possible. One potential way of accomplishing this is to use the information from the digital mammogram to help predict the background radiopharmaceutical distribution. With this in mind, we retrospectively investigated the degree of spatial correlation between the distribution of background activity and the distribution of radiodense breast tissue in normal breasts. Using a histogram-based analysis, we have quantified the degree of correlation in 16 images obtained from a total of 8 patients. We also used the mammographic images to quantify the radiographic density of each breast. Our results suggest that spatial correlation between areas of high radiopharmaceutical uptake and parenchymal density exists in the most dense regions of the breast for either extremely dense or heterogeneously dense breasts. High correlation was also observed for some homogeneously fatty breasts. In the latter case however, variation in breast thickness appeared to be the cause of the increased correlation. Correlation properties are approximately equal in both right and left breasts for a particular patient, except in cases exhibiting focal radiotracer uptake in a lesion. Although our preliminary results suggest that correlation between radiopharmaceutical uptake and parenchymal density exists, the number of cases thus far is too small for definitive conclusions. In addition, the planar nature of the dual modality scans imposes an inherent limitation on our ability to take into account attenuation of the emitted gamma radiation, which thus constitutes an uncontrolled variable in the correlation analysis. In principle, this problem can be eliminated by 3-dimensional imaging.