Mariano Busso

ArteFill : A long-lasting injectable wrinkle filler material-summary of the U.S. Food and Drug Administration trials and a progress report on 4- to 5-year outcomes

Summary: ArteFill, the successor product to Artecoll, is an injectable wrinkle filler composed of polymethylmethacrylate microspheres and bovine collagen, which offers long-lasting and probably permanent augmentation of wrinkles and skin contour deformities. The pivotal U.S. Food and Drug Administration study consisted of 251 subjects at eight centers in the United States who received injections of ArteFill or bovine collagen dermal filler (control) in 1334 wrinkles of the glabella, nasolabial folds, radial upper lip lines, and corners of the mouth. The efficacy data generated by masked observers using a photographic Facial Fold Assessment Scale demonstrated a significant improvement with ArteFill compared with collagen at 6 months (p < 0.001) in the nasolabial folds. In the ArteFill group, 12-month follow-up was obtained for 111 subjects (86.7 percent) and showed persistence of significant wrinkle correction. A subgroup of 69 patients who received ArteFill were recalled 4 to 5 years later. Five patients reported six late adverse events that occurred from 2 to 5 years after the initial injection; four of the adverse events were mild cases of lumpiness and two were severe. The total number of late adverse events was six of 272 (2.2 percent) wrinkles injected. Among the 272 wrinkles evaluated at 5 years, two events (0.7 percent) in one patient were rated as severe (a nodular, minimally inflammatory to noninflammatory reaction in both nasolabial folds). Investigator Facial Fold Assessment ratings at 4 to 5 years were improved from baseline by 1.67 points (p < 0.001).

Calcium hydroxylapatite (Radiesse) for correction of the mid- and lower face: consensus recommendations.

Summary: Restoring volume in the middle and lower portions of the face is becoming an indispensable component of modern facial rejuvenation. Radiesse (BioForm Medical, San Mateo, Calif.) is an injectable filler material composed of synthetic calcium hydroxylapatite microspheres (30 percent) suspended in an aqueous carrier gel (70 percent). At present, Radiesse is indicated in the United States for correction of moderate to deep nasolabial folds and for correction of the signs of facial fat loss (lipoatrophy) in people with human immunodeficiency virus. Its off-label use in other facial aesthetic indications is widely reported in the literature. The ability of Radiesse to provide immediate and durable effects has fueled interest in its use for expanded aesthetic applications, particularly in the middle and lower face. The authors’ consensus panel, consisting of a cross-section of experts in plastic surgery, facial plastic surgery, and dermatology, was convened to review the scientific literature and compare clinical experiences regarding the use of calcium hydroxylapatite. This report describes the characteristic effects of aging in the middle and lower face and reviews the composition of calcium hydroxylapatite, its safety and durability, and its appropriate use in a variety of facial applications, including nasolabial folds, correction of human immunodeficiency virus–associated lipoatrophy, augmentation of the malar, submalar, and zygomatic regions, and correction of oral commissure defects, marionette lines, and prejowl sulcus. Recommendations for Radiesse use in each area, including anesthesia, and injection techniques are provided. Measures for enhancing patient comfort, anticipating and minimizing potential complications, and optimizing aesthetic results are also discussed.

Hand augmentation with Radiesse® (Calcium hydroxylapatite)

ABSTRACT:  The hand has remained a considerable treatment challenge, as new soft tissue fillers have arrived in the esthetic marketplace. The challenge has been the result of both the multiple visits required for treatment in, for example, autologous fat grafting and the simple management of pain in the innervated areas of the hand between the bones.

The benzylthio-pyrimidine U-31,355, a potent inhibitor of HIV-1 reverse transcriptase

U-31,355, or 4-amino-2-(benzylthio)-6-chloropyrimidine is an inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and possesses anti-HIV activity in HIV-1-infected lymphocytes grown in tissue culture. The compound acts as a specific inhibitor of the RNA-directed DNA polymerase function of HIV-1RT and does not impair the functions of the DNA-catalyzed DNA polymerase or the Rnase H of the enzyme. Kinetic studies were carried out to elucidate the mechanism of RT inhibition by U-31,355. The data were analyzed using Briggs-Haldane kinetics, assuming that the reaction is ordered in that the template:primer binds to the enzyme first, followed by the addition of dNTP, and that the polymerase is a processive enzyme. Based on these assumptions, a velocity equation was derived that allows the calculation of all the essential forward and backward rate constants for the reactions occurring between the enzyme, its substrates, and the inhibitor. The results obtained indicate that U-31,355 acts as a mixed inhibitor with respect to the template:primer and dNTP binding sites associated with the RNA-directed DNA polymerase domain of the enzyme. The inhibitor possessed a significantly higher binding affinity for the enzyme-substrate complexes, than for the free enzyme and consequently did not directly affect the functions of the substrate binding sites. Therefore, U-31,355 appears to impair an event occurring after the formation of the enzyme-substrate complexes, which involves either inhibition of the phosphoester bond formation or translocation of the enzyme relative to its template:primer following the formation of the ester bond. Moreover, the potency of U-31,355 depends on the base composition of the template:primer in that the inhibitor showed a much higher binding affinity for the enzyme-poly (rC):(dG)10 complexes than for the poly (rA):(dT)10 complexes.

An Investigation of Changes in Physical Properties of Injectable Calcium Hydroxylapatite in a Carrier Gel When Mixed with Lidocaine and with Lidocaine/Epinephrine

INTRODUCTION As physicians incorporate calcium hydroxylapatite (CaHA) into their aesthetic treatment regimens, the question has arisen of whether the addition of anesthetic agents to prefilled CaHA syringes might provide sufficient anesthetic prophylaxis to warrant reduction in conventional anesthetic pretreatment procedures. STUDY DESIGN Investigators sought to determine changes in the physical properties of CaHA induced by the addition of lidocaine and lidocaine with epinephrine into the prefilled CaHA syringe. The CaHA and gel carrier (CHM) were mixed with varying amounts of lidocaine and lidocaine with epinephrine to measure the number of passes back and forth for optimal homogeneity of lidocaine and CaHA in syringes, changes in viscosity, extrusion force, needle jam rates, elasticity, and pH. RESULTS Ten mixing passes appeared sufficient for homogeneity. Viscosities and extrusion forces of CHM/lidocaine blends decrease with increasing amount of lidocaine. Needle jams do not increase. The pH and elasticity of the CHM/lidocaine blend are essentially equivalent to those of CHM alone. Epinephrine added to lidocaine did not alter the results enough to reach statistical significance. CONCLUSIONS Addition of lidocaine to original CHM can be safely added without harmful changes in physical properties of the original soft tissue filler. Further studies are required to explore whether the addition of lidocaine to CHM alters patient discomfort, durability, and efficacy.

Bednar tumor (pigmented dermatofibrosarcoma protuberans) occurring in a site of prior immunization: Immunochemical findings and therapy

Bednar tumor is a rare pigmented variant of dermatofibrosarcoma protuberans (DFSP). Because of its rarity, information is lacking regarding the optimal therapy and potential utility of immunohistochemistry in diagnosis. We report a case of Bednar tumor in which the diagnosis was aided by immunohistochemistry for CD34, an antigen known to be expressed in DFSP but not previously reported in Bednar tumor. Our case was also striking because it represents the first reported appearance of a Bednar tumor at a site of prior immunization, a phenomenon previously noted in some cases of DFSP. The patient was treated effectively with Mohs surgery and is without recurrence at 9 months.

Controlled, Randomized Study of Pain Levels in Subjects Treated with Calcium Hydroxylapatite Premixed with Lidocaine for Correction of Nasolabial Folds

BACKGROUND Calcium hydroxylapatite (CaHA) has been administered after nerve block injection of anesthetic agents. OBJECTIVES This prospective, randomized, split‐face, single‐blind study (50 subjects) assessed the pain reduction, safety, and effectiveness of premixing CaHA with 2% lidocaine for the treatment of nasolabial folds (NLFs). METHODS AND MATERIALS Subjects were randomized to receive treatment with CaHA alone in one NLF (control) and with CaHA premixed with lidocaine in the other NLF (treatment). Subjects completed pain assessments using a validated visual analog scale at specified time points immediately after injection, 1 hour after injection, and 1 month later. Subjects also indicated relative pain experience and preference assessments. Investigators completed aesthetic assessments at 2 weeks and 1 month. Subjects and investigators recorded adverse events. RESULTS Subjects reported statistically significantly less pain in the treatment fold than in the control fold and expressed unanimous preference for the treatment injection over the control. Aesthetic results were essentially equivalent for both treatments. CONCLUSION Investigators concluded that CaHA premixed with lidocaine results in significant pain reduction during dermal filler injection while maintaining the aesthetic improvement of CaHA without lidocaine and demonstrating comparable local transient adverse events for treatment and control. BioForm Medical (San Mateo, CA) provided the soft tissue filler, lidocaine, and other necessary supplies used in this study. All authors are members of the Bioform Medical Education Faculty.

HIV-induced syncytium formation requires the formation of conjugates between virus-infected and uninfected T-cells in vitro

The transmission of HIV requires the interaction of the cell-surface CD4 receptor and the viral envelope glycoprotein. Experiments were performed to determine the role of other cell-surface molecules in the development of HIV-induced syncytia. Although CEM and MT-2 cells had similar cell-surface CD4 receptor densities, less than 1% of CEM cells and greater than 95% of MT-2 cells formed syncytia with H9 cells chronically infected with HIV-1 (H9-IIIB). When compared with CEM cells, MT-2 cells exhibited a 10-fold and threefold greater capacity to form homotypic and heterotypic conjugates with H9 cells, respectively. Increasing the conjugate formation capacity of CEM cells with the lectin wheat germ agglutinin led to a greater than 30-fold increase in the formation of syncytia with H9/IIIB cells. The formation of syncytia between MT-2 and H9/IIIB cells was magnesium-, energy-, temperature-, and actin-cytoskeleton-dependent, and could be inhibited (65%) by an anti-LFA-1 monoclonal antibody. The combination of anti-leukocyte function-associated antigen-1 (LFA-1) and anti-CD2 monoclonal antibodies resulted in a synergistic inhibition (89%) of syncytium formation. These results indicate that integrins and other cell-surface adhesion molecules regulate HIV-induced syncytium formation.

Soft-tissue augmentation with hyaluronic acid and calcium hydroxyl apatite fillers.

Soft‐tissue augmentation with hyaluronic acid and calcium hydroxyl apatite are among the most widely used minimally invasive cosmetic treatments for the correction of contour deficiencies and wrinkles of the face without the risk, recovery time, and expense of a major surgery. Training and experience in the art and science of fillers is essential for the successful creation of a more youthful and natural appearance. An understanding of the different products, the injection techniques, the indications, and the potential complications of each filler are paramount to success.

Multicenter, Randomized Trial Assessing the Effectiveness and Safety of Calcium Hydroxylapatite for Hand Rejuvenation

OBJECTIVE To assess the safety and effectiveness of calcium hydroxylapatite (Radiesse Dermal Filler; RDF) for hand rejuvenation. METHODOLOGY One hundred and one randomized patients received RDF in the hands or no treatment (controls) for 3 months. Controls were crossed over at 3 months, and all patients were followed for 12 months. Assessments include the Busso Hand Volume Severity Scale (BHVSS), Global Aesthetic Improvement Scale‐Revised (GAIS‐R), patient satisfaction, physician satisfaction, hand function, and safety. RESULTS At 3 months and 6 months, 66% and 56% of hands, respectively, showed at least a 1‐point improvement on the BHVSS. At the same time points, 89% and 75% of hands, respectively, were improved on the GAIS‐R. In the controlled analysis, treated hands were statistically better than controls. At 3 and 6 months, 86% and 88% of physicians, respectively, and 78% and 76% of patients, respectively, were satisfied; 66% indicated likelihood to return for future RDF treatments. Treatment did not affect hand function. Adverse events were generally short in duration and without serious complications. CONCLUSIONS Hands treated with RDF showed statistically and clinically significant improvement, with high patient and physician satisfaction and no serious adverse events. BioForm Medical (San Mateo, CA) provided the Radiesse soft tissue filler, funding, supplies and equipment for photographic documentation for this study. Dr. Mariano Busso owns shares in BioForm Medical, Inc, is a member of the companys Medical Education Faculty, and has received compensation for presentations about Radiesse to the medical community. Dr. Marion Moers‐Carpi owns no stock in BioForm but has received compensation for presentations about Radiesse to the medical community. The remaining physicians have nothing to disclose. David J. Howell, PhD, RRT (San Francisco, CA) provided assistance with editorial development of this manuscript.