Autologous Cultured Fibroblast Injection for Facial Contour Deformities: A Prospective, Placebo-Controlled, Phase III Clinical Trial

BACKGROUND: Previous data indicate that injections of autologous fibroblasts increase collagen formation, accompanied by a concomitant increase in thickness and density of dermal collagen. OBJECTIVE: The purpose of this study was to determine efficacy and side effects of autologous living fibroblast injections versus placebo in a randomized Phase III trial for the treatment of various facial contour defects. METHODS: This was a double-blind, randomized comparison of injectable living autologous fibroblast cells and placebo for the treatment of facial contour defects (N=215). Live fibroblasts (20 million/mL) or placebo (the transport medium without living cells) were given as three doses administered at 1- to 2-week intervals. Efficacy evaluations were performed 1, 2, 4, 6, 9, and 12 months after the first injection. RESULTS: Living fibroblasts produced statistically significantly greater improvements in dermal deformities and acne scars than did placebo. The difference between live fibroblast injections and placebo achieved statistical significance at 6 months (p<.0001). At 9- and 12-month follow-up, live fibroblast-treated patients continued to demonstrate benefit from treatment with response rates of 75.0 and 81.6%, respectively. No serious treatment-related adverse events were reported. CONCLUSIONS: Our results indicate that autologous fibroblast injections can safely and effectively produce improvements in rhytids, acne scars, and other dermal defects continuing for at least 12 months after injection.     

Developmental Toxicity of Dimethylacetamide by Inhalation in the Rat

Developmental Toxicity of Dimethylacetamide by Inhalation inthe Rat. SOLOMON, H. M., FERENZ, R. L., KENNEDY, G. L., ANDSTAPLES, R. E. (1991). Fundam. Appl. Toxicol. 16, 414–422.Dimethylacetamide (DMAC) is a widely used industrial solvent.It has been reported to be teratogenic when given to rats byinjection or following dermal application. Most of these studiesemployed large single doses and did not examine both the fetaland the maternal response. In this study, groups of pregnantCrl:CD rats were exposed to 32, 100, or 282 ppm DMAC by inhalationfor 6 hr/day from Days 6 through 15 of gestation (day on whichcopulation plug was detected was termed Day 1G). A control groupof chambered pregnant rats was exposed simultaneously to aironly. All female rats were euthanized on Day 21G. At 282 ppm,both maternal weight gain during the exposure period and fetalweight were significantly decreased and accompanied by a significantdose-response trend. These effects were not seen in rats inhalingeither 32 or 100 ppm. Fetal resorptions were not increased inany of the groups exposed to DMAC. Fetal incidences of external,visceral, or skeletal variations and malformations were similarbetween the test and control groups. Therefore, both fetal andmaternal toxicity were noted at 282 ppm and the no-observedadverse-effect level under these experimental conditions was100 ppm for both the dam and the conceptus. DMAC was not demonstratedto produce malformations in the rat fetus even at a level thatwas toxic to the dam.     

Chemical shift differences between free and Fab-bound peptide correlate with a two-stage selection of peptide sequences from a random phage display library to delineate critical and non-critical residues for antibody recognition

Epitope libraries provide a method to identify peptide ligands for antibodies, receptors or other binding proteins. As such, they provide a powerful tool to rapidly identify lead ligands in the drug discovery process. In an attempt to correlate structural information with the results from peptide screening, we have used NMR spectroscopy of peptide/antibody complexes to demonstrate that core residues identified through a two-stage selection process undergo a larger structural change upon binding antibody than do positions in the peptide amenable to a variety of side chains. The model system used was the M2 monoclonal antibody/Flag? octapeptide epitope system. We have analyzed two peptides: Ac-Asp-Tyr-Lys-Leu-Gly-Asp-Asp-Leu-NH₂ (peptide l), which contains several non-core positions randomized, and Ac-Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Leu-NH₂ (peptide 2), which closely corresponds to the original Flag? sequence. Enrichment of the peptides with ¹⁵N facilitated the investigation by permitting spectral editing of the peptide resonances in the presence of antibody. For peptide 1 the absolute shifts for the free vs. Fab-bound peptide were found to be largest for the amide groups of Asp-1 and Asp-6, in agreement with classification of these residues as critical by the phage display library selection process. For peptide 2 the largest absolute shifts were observed for Asp-1 and Asp-4, with the other aspartic acid residues also showing significant but smaller changes. © Munksgaard 1995.     

Predictive capacity of the AUDIT questionnaire for alcohol-related harm

The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item questionnaire designed to screen for hazardous and harmful alcohol consumption. We examined its ability to predict alcohol-related illness and social problems, hospital admission and mortality over a 2–3-year period. At initial interview, 330 ambulatory care patients were assessed using a detailed interview including the AUDIT questions and laboratory tests. After 2–3 years, 250 (76%) subjects were reassessed and their experience of alcohol-related harm determined. Of those who scored eight or more on A UDIT at initial interview, 61 % experienced alcohol-related social problems compared with 10% of those with lower scores (p < 0.0001); they also had a significantly greater experience of alcohol-related medical disorders and hospitalization. A UDIT score was a better predictor of social problems and of hypertension than laboratory markers. Its ability to predict other alcohol-related illnesses was similar to the laboratory tests. However, gamma glutamyltransferase was the only significant predictor of mortality. We conclude that A UDIT should prove a valuable tool in screening for hazardous and harmful alcohol consumption so that intervention can be provided to those at particular risk of adverse consequences.     

Influencing physician response to prenatal substance exposure through state legislation and work-place policies

Little research attention has focused on ways to encourage physician response to prenatal substance exposure. We report initial results from a study examining the impact of state laws and work-place policies on physician response by combining legal analyses and data from a national physician survey. Our findings indicate that the message that laws and policies exist usually does not reach physicians. However, when the message does come through, some physician behaviors are influenced. In particular, physicians in states with clearer policies and behavioral expectations are significantly more likely to know and understand the law than physicians in other states. Further, believing that a work-place protocol on prenatal substance exposure exists is associated with significantly increased likelihood of an active response in case vignettes portraying prenatal substance exposure. The findings suggest that state legislative behaviors may increase physician response to prenatal substance exposure, but that response depends on the nature of the policy and on efforts to disseminate it.     

Preservation of All Chordae Tendineae and Papillary Muscle During Mitral Valve Replacement with a Tilting Disc Valve

Mitral valve replacement was performed in 21 patients using a surgical technique that preserves the entire papillary muscle and chordal apparatus. With this technique, the anterior mitral leaflet is split from the center of the free edge toward the annulus. Bilateral incisions are made from the proximal end of this split to the two mitral commissures, detaching the anterior leaflet from the annulus. These two halves of the leaflet, with all chordae intact (corresponding to the anterolateral and posteromedial papillary muscles), are judiciously trimmed to remove areas of leaflet untethered by chordae tendineae and (when necessary) fibrous thickening; then swung posteriorly and sutured to the posterior mitral annulus using mattress sutures with pledgets. This surgical technique is expected to favor the preservation of left ventricular function and avoid occurrence of irreversible left ventricular dilation/dysfunction, and has been used successfully for calcific and degenerative etiologies, using both tilting disc valves and porcine bioprostheses. It is especially useful in the implantation of tilting disc and bileaflet mechanical prostheses because anterior subvalvular chordae tissue may interfere with the disc excursion and relocated to the posterior leaflet annulus.     

Preventing accidental injury to young children in the home using volunteers

Accidental injury in the home is a major cause of death andill-health among young children. Reducing home safety hazardsby the use of safety devices such as stair barriers and safetytaps has the potential to prevent home injuries. Little is knownabout levels of home safety hazards or how to encourage parentsto reduce hazards. The Safe Place Project examined parents'knowledge of home safety and the prevalence of safety hazardsin homes where there were young children. The study also evaluatedthe effectiveness of a low-cost strategy aimed at reducing homesafety hazards. The strategy used trained volunteers to providehome safety checks and tailored safety education in conjunctionwith increasing the availability of home safety devices. Onehundred and six families with young children participated inthe project. Some homes contained many hazards, with 43% ofthe sample having more than 10 home safety hazards. At follow-up,the intervention group showed a significant reduction in homehazards and a trend towards an increase in knowledge of homesafety.