The optimal filler: immediate and long-term results with emulsified silicone (1,000 centistokes) with cross-linked hyaluronic acid.

BACKGROUND: Silicone is one of the oldest and longest lasting of the dermal fillers. Microdroplet silicone injections have proven to be safe and effective. This paper describes how to obtain microdroplet silicone (1,000 centistokes) in a consistent manner, including a discussion of its efficacy and safety. METHODS AND MATERIALS: A simple, permanent method of tissue augmentation is described. U.S. Food and Drug Administration- approved liquid silicone (Silikon®) is emulsified with cross-linked hyaluronic acid through a Luer-Lok to Luer-Lok connector between two 3-cc syringes. This stable emulsion is injected through a 27G needle or through a 25G or 27G microcannula into the middermis, subcutaneous tissue, or periosteum. RESULTS: The results of 95 cases are described. The emulsion is most beneficial for distensible acne valleys, nasolabial folds, glabellar frown lines, augmentation of the vermilion border of the lips, and projection of the nose, cheekbones, and chin. Exterior nasal deviations and soft tissue defects are also improved. Complications are minimal and include temporary bruising, erythema, and mild edema. Any temporary small nodules are easily leveled with massage. Occasionally, it takes a repeat session at 1 month to completely elevate depressions. The resulting elevations remain stable during the 2-year follow-up period. No silicone granulomas have developed. CONCLUSIONS: This methodology has replaced many indications for temporary, semipermanent, or permanent fillers.

Filler injections with the blunt-tip microcannula.

BACKGROUND: Microcannulas with blunt tips for filler injections have recently been developed for use with dermal fillers. Their utility, ease of use, cosmetic outcomes, perceived pain, and satisfaction ratings amongst patients in terms of comfort and aesthetic outcomes when compared to sharp hypodermic needles has not previously been investigated. OBJECTIVE: To compare injections of filler with microcannulas versus hypodermic needles in terms of ease of use, amount of filler required to achieve desired aesthetic outcome, perceived pain by patient, adverse events such as bleeding and bruising and to demonstrate the advantages of single-port injection technique with the blunt-tip microcannula. MATERIALS AND METHODS: Ninety-five patients aged 30 to 76 years with a desire to augment facial, décolleté, and hand features were enrolled in the study. Subjects were recruited in a consecutive manner from patients interested in receiving dermal filler augmentation. Each site was cleaned with alcohol before injection. Anesthesia was obtained with a topical anesthesia peel off mask of lidocaine/tetracaine. Cross-linked hyaluronic acid (20 mg to 28 mg per mL) was injected into the mid-dermis. The microcannula or a hypodermic needle was inserted the entire length of the fold, depression or lip and the filler was injected in a linear retrograde fashion. The volume injected was variable, depending on the depth and the extent of the defect. The injecting physician assessed the ease of injection. Subjects used the Visual Analog Scale (0-10) for pain assessment. Clinical efficacy was assessed by the patients and the investigators immediately after injection, and at one and six months after injection using the Global Aesthetic Improvement Scale (GAIS) and digital photography. RESULTS: Overall, the Global Aesthetic Improvements Scale (GAIS) results were excellent (55%), moderate (35%), and somewhat improved (10%) one month after the procedure, decreasing to 23%, 44%, and 33%, respectively, at the six month evaluation. There was no significant differences in the GAIS score between the microcannula and the hypodermic needle. However, the Visual Analog Scale for pain assessment during the injections was quite different. The pain was described as 3 (mild) for injections with the microcannula, increasing to 6 (moderate) for injections with the hypodermic needle. Bruising and ecchymosis was more marked following use of the hypodermic needle. CONCLUSION: Using the blunt-tip microcannula as an alternative to the hypodermic needles has simplified filler injections and produced less bruising, echymosis, and pain with faster recovery.

Virtually painless local anesthesia: diluted lidocaine proves to be superior to buffered lidocaine for subcutaneous infiltration.

BACKGROUND: Many physicians believe that buffering local anesthetics with sodium bicarbonate is the best technique for reducing the pain and discomfort associated with subcutaneous infiltration. OBJECTIVE: To compare the level of pain and discomfort associated with subcutaneous infiltration of lidocaine diluted with normal saline to that associated with traditionally buffered lidocaine. PATIENTS/METHODS: In a prospective, double-blind trial, 31 patients were asked to use a visual analog scale to rank the level of pain and discomfort caused by two different solutions of lidocaine with epinephrine. Solution A: 3 mL of 1% lidocaine + epinephrine in 30 mL of bacteriostatic 0.9% sodium chloride in a 1:10 ratio, in which each mL contained 9 mg of sodium chloride and 9 mg of benzyl alcohol. Solution B: 5 mL of 8.4% sodium bicarbonate solution and 50 mL of 1% lidocaine + epinephrine in a 1:10 ratio. RESULTS: Twenty-eight out of 31 patients reported that the solution of lidocaine diluted with normal saline was the least painful upon injection. CONCLUSION: Pain and discomfort during subcutaneous injection of lidocaine can be reduced by diluting the anesthetic with normal saline in a 1:10 ratio.

Advances in the treatment of keloids.

Occurring with higher proportions in skin of color, keloid formation is seen in individuals of all races, with the lowest incidence in albinos. Interestingly, prevalence of keloids is correlated to skin pigmentation, with dark-skinned individuals suffering disproportionately. Many factors are taken into consideration when deciding which modalities to use in the treatment of keloids, including size, anatomical site, cause, symptoms, duration of treatment and not least importantly, pigmentation of the patient. In patients with skin of darker color it is necessary to communicate the effects these treatments may have on epidermal pigmentation to the patient. Of course, the best treatment for keloids remains prevention. Physicians should be alert to delays in wound healing, persistent erythema, or pruritus as impending symptoms of possible keloid formation and make all reasonable attempts to reduce inflammation and tension on the skin with appropriate methods.

Comparison of short-pulsed and long-pulsed 532 nm lasers in the removal of freckles.

The purpose of this study was to compare the efficacy and safety of the 532 nm long-pulsed laser (10 ms) with that of the 532 nm short-pulsed laser (10 ns) for freckle removal. Currently, the gold standard for treatment is the short-pulsed laser. Recently, several long-pulsed lasers have been introduced for both hair removal and the treatment of freckles. To our investigative team's knowledge, no controlled experiments have been performed to compare the safety and efficacy of long-pulsed versus short-pulsed lasers for the treatment of freckles. This was a 4-week trial, and all patients had three freckles that were randomly allocated to be treated with short-pulse laser, long-pulse laser, or to receive no treatment (control). All patients had three freckles that were randomly selected to be treated with short-pulse 532 nm Medlite IV laser (10 n, 1 J/cm(2)), or long-pulse 532 nm Aura laser (10 ms, 1 J/cm(2)) or to remain as a control (no treatment). The laser treatment was only performed once, followed by a 1-day and a 1-month follow-up visit. Freckle size was determined by a novel surface area measurement technique that was created by our research staff. The study included 17 sets of freckles (three in each set). All of the lesions which received the short-pulsed laser treatment had immediate whitening of the lesions, which turned into dry scabs the next day. None of the freckles treated in the long-pulsed group or control group developed immediate whitening or scabs. No blisters or ulcers developed. The average pain score in the short-pulsed laser group was 2-3 out of 10, while it was 0 out of 10 in the long-pulsed laser group. All scabs that developed in the short-pulsed laser group fell off between days 6 and 12 (average 8 days). The outcome of this study verified the appropriate treatment of freckles. The study confirmed that when the same energy settings, short-pulsed laser is the more effective laser treatment regimen (when compared with the long-pulsed laser), with high tolerability and minimal side effects for patients with skin types I to IV.

Comparison of the effects of short- and long-pulse durations when using a 585-nm pulsed dye laser in the treatment of new surgical scars.

More than 70 million surgical procedures are performed annually in the USA with the majority involving a skin lesion and almost all individuals in their lifetime will have one or more surgical procedures resulting in scars. Patients and physicians alike are thereby motivated to improve the cosmetic outcome of scars. Prior studies have shown that the pulsed dye laser (PDL) is effective in improving the quality and appearance of the scar when using the 585-nm PDL immediately after the removal of sutures. Most published studies used a pulse duration of 450 micros, which along with the other study parameters, has led to an overall improvement of the scars. However, a pulse duration of 1.5 ms is also available when using the pulsed dye laser and it should theoretically cause fewer side-effects. To our knowledge, there are no other studies comparing the effectiveness of different pulse durations in the treatment of surgical scars starting on the day of suture removal. The purpose of this study is to compare the effect of different pulse durations (450 micros vs. 1.5 ms) in the treatments of postsurgical linear scars immediately after suture removal when using the 585-nm pulsed dye laser (PDL). Twenty non-hospitalized male and female patients (older than 18 years of age) with skin types I-IV and with postoperative linear scars measuring at least 2.1 cm were enrolled in this prospective study. Scars were randomly divided into three equal sections. The different fields were randomly chosen to receive treatment (two out of three fields) or remain as control (one field). The two fields chosen to be treated received treatment with the 585-nm PDL using a 7-mm spot size at 4.0 J. One of the treated sections was randomly selected to receive a pulse duration of 450 micros, and the other section to receive a 1.5-ms pulse. The remaining scar section was designated as control (no treatment). The three sections were mapped and recorded. The patient received treatment immediately after the sutures were removed from the wound and then monthly for 3 months. Evaluations were performed before each treatment and 1 month after the last treatment. The short-pulse and long-pulse 585-nm PDL-treated sections demonstrated a statistically significant overall average improvement of the VSS of 92 and 89%, respectively, compared to 67% for the control site (Fig. 1). Further, for individual parameters of the Vancouver scar scale (VSS), there were significant (p < 0.05) differences between control and treatment groups for all parameters, but there were no differences between the short- and long-pulse treatment groups for any parameter. Both short-pulse and long-pulse PDL are safe and effective in improving the quality and cosmetic appearance of surgical scars in skin type's I-IV starting on the day of suture removal with no significant difference between the two pulse durations.

Anaphylaxis to IGIV in immunoglobulin-naïve common variable immunodeficiency patient in the absence of IgG anti-IgA antibodies: successful administration of low IgA-containing immunoglobulin.

Although severe reactions to immunoglobulin preparations have been frequently reported, IgE antibodies against IgA are usually not investigated; and occur predominantly in previously sensitized patients. The purpose is to report anaphylaxis to IGIV during initial infusion in a patient with common variable immunodeficiency with absent IgA without prior sensitization and in the absence of detectable IgG anti-IgA antibodies, and positive skin tests for immediate hypersensitivity to four different preparations of IGIV, one subcutaneous immunoglobulin preparation, and to purified IgA. Patient was treated without side effects with IGIV preparation depleted of IgA to which immediate hypersensitivity skin test was negative. This case demonstrates that patients with CVID with no IgA and without prior exposure to immunoglobulin or plasma may develop anaphylaxis following initial infusion of IGIV, which appears to be due to IgE anti-IgA, and independent of IgG anti-IgA antibodies. Since there is no good correlation between anaphylaxis/anaphylactic reactions and IgG anti-IgA antibodies, and IgE anti-IgA antibody test is commercially unavailable, we suggest that the patients with CVID with absence of IgA might be skin tested for immediate hypersensitivity prior to initiation of immunoglobulin administration. However, such recommendation may require studies on a large number of patients with CVID with no detectable IgA.

Effect of behavioral interventions on insulin sensitivity and atherosclerosis in the Watanabe heritable hyperlipidemic rabbit.

OBJECTIVE: A previous study suggested that insulin metabolic variables play a role in the progression of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. The present study sought to determine: 1) if young, individually caged WHHLs are insulin-resistant relative to New Zealand white (NZW) rabbits and 2) whether dietary or exercise interventions can improve insulin sensitivity and slow the development of atherosclerosis in these animals. METHODS: Forty-two WHHLs were assigned to a dietary, exercise, or control condition, and 12 NZWs were used as a comparison control group. The intervention ran from 3 to 7 months of age, and all animals received an intravenous glucose tolerance test at the beginning and end of the intervention. RESULTS: WHHLs were insulin-resistant relative to NZWs at 3 months of age. Whereas the dietary intervention was effective in controlling insulin resistance, WHHLs in the exercise group without dietary restriction and the control group exhibited significant increases in insulin resistance. No intervention significantly influenced the progression of atherosclerosis. CONCLUSIONS: Young WHHLs are insulin-resistant during an early period when atherosclerosis is developing rapidly. Dietary restriction, but not exercise without weight control, is effective in controlling insulin metabolic variables in the WHHL model. Although dietary intervention can reduce cardiovascular risk factors such as insulin resistance, it is not effective in slowing the development of atherosclerosis in these genetically dyslipidemic animals. Similarly, exercise training, without dietary control, does not influence the progression of disease in WHHLs.

Lentiviral vector-mediated transduction of neural progenitor cells before implantation into injured spinal cord and brain to detect their migration, deliver neurotrophic factors and repair tissue.

PURPOSE: Stem cells represent an attractive source for cell replacement therapy in neurological disorders due to their self-renewal and multi-potency. Genetic manipulation of these cells may allow controlled release of therapeutic proteins, suppress immune rejection, or produce essential neurotransmitters. Furthermore, when the expression cassette is incorporated into the host genome ex vivo, this technique also may be used as a method to trace cells following implantation into tissues of interest. METHODS: We explored the possibility of transducing pluripotent fetal rat cortical neural progenitor cells (NPCs) using lentiviral vectors encoding the green fluorescent protein (GFP) or neurotrophic factors (BDNF, CNTF, D15A, GDNF, MNT and NT-3) prior to implanting these cells into the contused spinal cord or injured brain. RESULTS: In vitro staining of these cells for neural markers (such as nestin, GFAP, Tuj-1 and RIP) after transduction did not reveal any significant difference from non-transduced cells. When they were transduced with a vector encoding CNTF or MNT, however, cells started expressing GFAP in vitro. Following delayed (1 week) implantation into the lesion site of the moderately contused rat spinal cord or the injured brain, transduced cells survived up to 12 weeks post-implantation (the longest time point examined) and most of the NPCs turned into an astrocytic phenotype in the spinal cord, but not in the brain. Nestin and GFP positive cells were detected in the brain, but not in the spinal cord lesion. GFP positive cells in the spinal cord migrated rostrally and caudally from the lesion/implantation site towards uninjured tissue. CONCLUSIONS: Novel findings in this study are the longterm expression of a foreign gene in NPCs using lentiviral vectors; this enabled tracking of the cells following implantation. This expression also allowed the observation that NPCs developed differently in the injured spinal cord and brain. Moreover, NPCs could be transduced to overexpress neurotrophic factors. In sum, NPC survival and the long-term transgene expression that allows easy tracking of migrating cells make NPCs promising candidates for implantation into the injured spinal cord or brain and a potentially powerful tool to enhance regeneration when transduced ex vivo to produce therapeutic molecules.

Good syndrome presenting with CD8⁺ T-Cell large granular lymphocyte leukemia.

Good Syndrome is an adult-onset combined immunodeficiency defined by hypogammaglobulinemia, low or absent number of B cells, T cell deficiency and thymic tumor. We have characterized CD8+ T cells from a patient with Good syndrome that presented with CD8+T-cell large granular lymphocytic leukemia (LGL). Characterization of peripheral blood CD8+ T cells revealed that majority of CD8+ T cells were terminally differentiated effector memory phenotype (TEMRA; CD8+CCR7-CD45RA+), and were PD-1high (CD279), ICOSlow (CD278), and granzymehigh. Almost all CD8+ T cells were IFN-γ+. CD8 Treg (CD8+CD183+CCR7+CD45RA-) were decreased. TEMRA phenotype along with CD279high, demonstrates that these are exhausted CD8+ T cells. This phenotype along with CD278low may also explain severe T cell functional deficiency in our patient. In the present patient, T-LGL appears to be a clonal expansion of CD279+granzyme+IFN-γ+CD8+TEMRA cells. To best of our knowledge this is the first case of CD8+T-cell LGL leukemia associated with Good syndrome.

Double-blind, Placebo-controlled Study Assessing the Effect of Chocolate Consumption in Subjects with a History of Acne Vulgaris.

OBJECTIVE: To assess the effect of chocolate on acne exacerbation in males between the ages of 18 and 35 with a history of acne vulgaris. DESIGN: Double-blind, placebo-controlled, randomized, controlled trial. SETTING: Single-site, outpatient, research, clinical facility at an academic research institution. PARTICIPANTS: Fourteen men between the ages of 18 and 35 were assigned to swallow capsules filled with either unsweetened 100-percent cocoa, hydrolyzed gelatin powder, or a combination of the two, at baseline. MEASUREMENTS: Lesions were assessed and photographs were taken at baseline, Day 4, and Day 7. RESULTS: Of the 14 subjects, 13 completed this Institutional Review Board approved study. A statistically significant increase in the mean number of total acneiform lesions (comedones, papules, pustules, nodules) was detected on both Day 4 (p=0.006) and Day 7 (p=0.043) compared to baseline. A small-strength positive Pearson's correlation coefficient existed between the amount of chocolate each subject consumed and the number of lesions each subject developed between baseline and Day 4 (r=0.250), while a medium-strength positive correlation existed between baseline and Day 7 (r=0.314). No serious adverse events occurred. CONCLUSION: It appears that in acne-prone, male individuals, the consumption of chocolate correlates to an increase in the exacerbation of acne.

Safety, efficacy, and patient acceptability of imiquimod for topical treatment of actinic keratoses.

Imiquimod, an immune-modulating imidazoquinoline compound, has been approved in topical formulation for the treatment of actinic keratoses, superficial basal cell carcinomas, and external genital warts. Its use in the treatment of field cancerization, in particular, has been rapidly evolving. With the recent approval of a new drug application for a new concentration, as well as generic formulations, this drug has emerged at the forefront of treatment for actinic keratoses, with improved dosage scheduling and more patients having access to generic options. In the nearly 15 years since its original approval by the Food and Drug Administration for the treatment of actinic keratoses in 1997, topical imiquimod has been reviewed and studied extensively, not only for its safety and efficacy, but also for its tolerability in patients. This paper provides an indepth review of the literature, and provides clinical evidence for its inclusion in the arsenal of treatment options for patients with actinic keratoses.