Eyal Winkler

Systemic dysregulation of CEACAM1 in melanoma patients.

It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival. Multivariate analysis with neutralization of LDH showed that increased serum CEACAM1 carries a hazard ratio of 2.40. In vitro, soluble CEACAM1 was derived from CEACAM1(+), but neither from CEACAM1(−) melanoma cells nor from CEACAM1(+) lymphocytes, and directly correlated with the number of CEACAM1(+) melanoma cells. Production of soluble CEACAM1 depended on intact de novo protein synthesis and secretion machineries, but not on metalloproteinase function. An unusually high percentage of CEACAM1(+) circulating NK and T lymphocytes was demonstrated in melanoma patients. CEACAM1 inhibited killing activity in functional assays. CEACAM1 expression could not be induced on lymphocytes by serum from patients with high CEACAM1 expression. Further, expression of other NK receptors was impaired, which collectively indicate on a general abnormality. In conclusion, the systemic dysregulation of CEACAM1 in melanoma patients further denotes the role of CEACAM1 in melanoma and may provide a basis for new tumor monitoring and prognostic platforms.

The use of video capture virtual reality in burn rehabilitation: the possibilities.

We independently explored the use of the Sony PlayStation II EyeToy (Sony Corporation, Foster City, CA) as a tool for use in the rehabilitation of patients with severe burns. Intensive occupational and physical therapy is crucial in minimizing and preventing long-term disability for the burn patient; however, the therapist faces a difficult challenge combating the agonizing pain experienced by the patient during therapy. The Sony PlayStation II EyeToy is a projected, video-capture system that, although initially developed as a gaming environment for children, may be a useful application in a rehabilitative context. As compared with other virtual reality systems the EyeToy™ is an efficient rehabilitation tool that is sold commercially at a relatively low cost. This report presents the potential advantages for use of the EyeToy™ as an innovative rehabilitative tool with mitigating effects on pain in burn rehabilitation. This new technology represents a challenging and motivating way for the patient to immerse himself or herself in an alternate reality while undergoing treatment, thereby reducing the pain and discomfort he or she experiences. This simple, affordable technique may prove to heighten the level of patient cooperation and therefore speed the process of rehabilitation and return of functional ability.

Seizures after flumazenil administration in a case of combined benzodiazepine and tricyclic antidepressant overdose

Flumazenil (Anexate®, Roche, Basel, Switzerland) is a specific, high-affinity, competitive inhibitor of the central nervous systems benzodiazepine γ-aminobutyric acid receptor, with high clinical efficacy in reversing the effects of benzodiazepine overdose (1, 2). Flumazenil is used in the emergenc

Nitrous oxide administered by the plastic surgeon for repair of facial lacerations in children in the emergency room.

Background: The purpose of this study was to investigate a means of providing pain relief during repair of facial lacerations in children in the emergency room. Methods: This study was conducted in the emergency room of a tertiary care, university-affiliated hospital. Fifty percent nitrous oxide was administered by the surgeon who sutured the laceration. A nurse monitored the child throughout the procedure. At the end of the procedure, pain scores were evaluated by the surgeon and nurse using the FLACC (face, legs, activity, cry, and consolability) scale, a structured observational-behavioral scale for measurement of pain. Results: Sixty patients between the ages of 1 and 16 years participated in the study. Of these, 15 were sutured using standard care (lidocaine infiltration), and 45 children received nitrous oxide in addition to lidocaine infiltration. Nitrous oxide was administered for an average of 11.9 ± 5.1 minutes (range, 4 to 30 minutes). Forty-three children recovered to preprocedure activity in less than 1 minute. Two children recovered in less than 3 minutes. Average FLACC scores during infiltration and suturing were significantly lower in the nitrous oxide group compared with controls (infiltration, 1.9 of 10 versus 9.7 of 10; suturing, 2 of 10 versus 8.8 of 10). Forceful restraining was necessary in all the controls, whereas in the nitrous oxide group mild force was required in only 15 percent. Seventy percent of the children receiving nitrous oxide had no side effects. Vomiting and nausea were the most common (17 percent), transient side effects. No respiratory or cardiovascular side effects occurred. Conclusions: Nitrous oxide can be safely administered by plastic surgeons while suturing facial lacerations in the emergency room. The fast onset and rapid recovery characteristics of nitrous oxide provide a convenient environment for performing short surgical procedures. This safe method for provision of analgesia and anxiolysis may be appealing to plastic surgeons for ambulatory procedures (e.g., suture removal, expander inflation, Botox injection, injection of various fillers) in pediatric and adult populations.

Ectopic PDX-1 expression directly reprograms human keratinocytes along pancreatic insulin-producing cells fate.

Background Cellular differentiation and lineage commitment have previously been considered irreversible processes. However, recent studies have indicated that differentiated adult cells can be reprogrammed to pluripotency and, in some cases, directly into alternate committed lineages. However, although pluripotent cells can be induced in numerous somatic cell sources, it was thought that inducing alternate committed lineages is primarily only possible in cells of developmentally related tissues. Here, we challenge this view and analyze whether direct adult cell reprogramming to alternate committed lineages can cross the boundaries of distinct developmental germ layers. Methodology/Principal Findings We ectopically expressed non-integrating pancreatic differentiation factors in ectoderm-derived human keratinocytes to determine whether these factors could directly induce endoderm-derived pancreatic lineage and β-cell-like function. We found that PDX-1 and to a lesser extent other pancreatic transcription factors, could rapidly and specifically activate pancreatic lineage and β-cell-like functional characteristics in ectoderm-derived human keratinocytes. Human keratinocytes transdifferentiated along the β cell lineage produced processed and secreted insulin in response to elevated glucose concentrations. Using irreversible lineage tracing for KRT-5 promoter activity, we present supporting evidence that insulin-positive cells induced by ectopic PDX-1 expression are generated in ectoderm derived keratinocytes. Conclusions/Significance These findings constitute the first demonstration of human ectoderm cells to endoderm derived pancreatic cells transdifferentiation. The study represents a proof of concept which suggests that transcription factors induced reprogramming is wider and more general developmental process than initially considered. These results expanded the arsenal of adult cells that can be used as a cell source for generating functional endocrine pancreatic cells. Directly reprogramming somatic cells into alternate desired tissues has important implications in developing patient-specific, regenerative medicine approaches.

A new modality in the treatment of actinic cheilitis using the Er:YAG laser.

Background. Cheilitis is a precancerous skin lesion most often affecting the lower lip. We describe a technique in which this disorder can be treated using Er:YAG laser vaporization. The Er:YAG laser wavelength at 2940 nm lies in a very strong water absorption peak; tissue interaction results mainly in vaporization with minimal heat conduction to adjacent tissue. Objective. To evaluate the efficacy and outcome of a new modality in the treatment of actinic cheilitis with the Er:YAG laser. Methods. Between 2002 and 2005, 12 patients with actinic cheilitis were treated at our institute with the Er:YAG laser. All patients were cured with no recurrence to date, and none suffered postoperative complications. Results: Patients were men and women aged between 37 and 71 years. The healing duration varied from 7 to 30 days (mean 22.33±6.91 days) and the follow‐up ranged from 8 months to 3 years (mean 23.16±9.48 months). No recurrences were detected in our study. Conclusion. Using the Er:YAG laser provides accurate tissue ablation, giving a very satisfactory cosmetic result, with a short healing period, no lip deformity and no sensation loss.

The Origin of Human Mesenchymal Stromal Cells Dictates Their Reparative Properties

Background Human mesenchymal stromal cells (hMSCs) from adipose cardiac tissue have attracted considerable interest in regard to cell‐based therapies. We aimed to test the hypothesis that hMSCs from the heart and epicardial fat would be better cells for infarct repair. Methods and Results We isolated and grew hMSCs from patients with ischemic heart disease from 4 locations: epicardial fat, pericardial fat, subcutaneous fat, and the right atrium. Significantly, hMSCs from the right atrium and epicardial fat secreted the highest amounts of trophic and inflammatory cytokines, while hMSCs from pericardial and subcutaneous fat secreted the lowest. Relative expression of inflammation‐ and fibrosis‐related genes was considerably higher in hMSCs from the right atrium and epicardial fat than in subcutaneous fat hMSCs. To determine the functional effects of hMSCs, we allocated rats to hMSC transplantation 7 days after myocardial infarction. Atrial hMSCs induced greatest infarct vascularization as well as highest inflammation score 27 days after transplantation. Surprisingly, cardiac dysfunction was worst after transplantation of hMSCs from atrium and epicardial fat and minimal after transplantation of hMSCs from subcutaneous fat. These findings were confirmed by using hMSC transplantation in immunocompromised mice after myocardial infarction. Notably, there was a correlation between tumor necrosis factor‐α secretion from hMSCs and posttransplantation left ventricular remodeling and dysfunction. Conclusions Because of their proinflammatory properties, hMSCs from the right atrium and epicardial fat of cardiac patients could impair heart function after myocardial infarction. Our findings might be relevant to autologous mesenchymal stromal cell therapy and development and progression of ischemic heart disease.

Silicone-Based Scar Therapy: A Review of the Literature

Hypertrophic and keloid scars still are among the banes of plastic surgery. In the treatment arsenal at the disposal of the plastic surgeon, topical silicone therapy usually is considered the first line of treatment or as an adjuvant to other treatment methods. Yet, knowledge concerning its mechanisms of action, clinical efficacy, and possible adverse effects is rather obscure and sometimes conflicting. This review briefly summarizes the existing literature regarding the silicone elastomer’s mechanism of action on scars, the clinical trials regarding its efficacy, a description of some controversial points and contradicting evidence, and possible adverse effects of this treatment method. Topical silicone therapy probably will continue to be the preferred first-line treatment for hypertrophic scars due to its availability, price, ease of application, lack of serious adverse effects, and relative efficacy. Hopefully, future randomized clinical trials will help to clarify its exact clinical efficacy and appropriate treatment protocols to optimize treatment results.

Stensen duct rupture (sialocele) and other complications of the Aptos thread technique.

Background: The Aptos thread technique is a mode of uplifting the flabby soft tissue of the aging face. Permanent suture material made of polypropylene monofilament with dents is used in this technique. This procedure is gaining popularity throughout the world. According to the literature, several hundred Aptos procedures have been performed, and no major complications have been reported yet. Methods: Two adult women presented shortly after the Aptos thread insertion. They sustained devastating results. A close study was performed to understand and learn the potential complications. Results: The authors present two major complications, a rare case of Stensens duct laceration and a case of chronic inflammation mandating surgical treatment. Conclusions: Describing complications may teach plastic surgeons more about this method and how to avoid similar devastating side effects in the future.

Treatment of Postdermabrasion Facial Hypertrophic and Keloid Scars with Intralesional 5-Fluorouracil Injections

Hypertrophic and keloid scarring is a known complication of dermabrasion facial resurfacing, although only a very small fraction of patients experience it. Treatment with intralesional corticosteroid injections and flashed pumped vascular dye laser is recommended in the literature. The treatment of keloid and hypertrophic scars using intralesional 5-fluorouracil (5-FU) injections has been well described, but there is no literature regarding use of the same treatment for postdermabrasion hypertrophic and keloid scars. In this case report, we describe a 67-year-old woman with persistent postdermabrasion facial hypertrophic and keloid scars that were treated at our scar clinic using intralesional 5-FU injections.