Improving the quality of life in melanoma: the role of the CO(2) laser.

The cutaneous manifestations of late-stage melanoma can be distressing both physically and psychologically. In our department, we are sometimes referred a subgroup of patients where, despite adequate initial treatment, the disease manifests as cutaneous metastases that can be very symptomatic. The referring physician, having deemed other modalities of treatment inappropriate, may direct such patients to us at the regional laser centre for local control. Where no treatment option exists to cure or prolong life, very often, the simplest and safest option is the best. The CO(2) laser can be used to successfully ablate the lesions and be performed on a day-case basis. A worthwhile degree of palliation can be provided. As illustrated by three cases from our department, this form of treatment can be executed as and when required and results in an improved quality of life for these patients.

The management of periorbital fat excess in haemangioma involution.

Haemangioma of infancy is a common birthmark. As spontaneous involution is the rule, it is usually treated conservatively. Periorbital haemangiomata may require intervention if symptomatic and this may be early or late, where plastic surgery may be required. It has not previously been recognised that deep periorbital lesions may lead to a baggy appearance of the eyelids because of excess fatty tissue. The management of this condition is described in different clinical presentations illustrated by three female patients with a history of infantile periorbital haemangioma. Two were treated by blepharoplasty, during which an excess of fatty tissue was found, deep to the orbital septum. Birthmark stigmata were eradicated and symmetry was achieved.

Ubiquitination and degradation of the anti-apoptotic protein ARC by MDM2.

Current evidence shows that cardiomyocyte apoptosis plays a central role in the pathogenesis of myocardial disease and that reactive oxygen species is critically responsible for mediating cardiomyocyte apoptosis in both ischemia-reperfusion injury and dilated cardiomyopathy. ARC (Apoptosis Repressor with Caspase recruitment domain) is an anti-apoptotic protein that is found abundantly in terminally differentiated cells such as cardiomyocytes. The ARC knock-out mouse developed larger infarct in response to ischemia-reperfusion and transitioned more rapidly and severely to dilated cardiomyopathy following aortic constriction. In addition, ARC protein levels are decreased in human dilated cardiomyopathy and when cardiomyocytes are exposed to oxidative stress in vitro, but the mechanisms regulating ARC protein levels are not known. Here we show that degradation of ARC is dependent on the p53-induced ubiquitin E3 ligase, MDM2. Oxidative stress reduced ARC levels and up-regulated MDM2. MDM2 directly accelerated ARC protein turnover via ubiquitination and proteasomal-dependent degradation. This activity requires a functioning MDM2 ring finger domain because the MDM2(C464A) mutant was unable to direct ARC degradation. Furthermore, ARC degradation requires MDM2, because MDM2 knock-out fibroblasts showed defective ARC degradation that could be rescued by MDM2. Proteasomal inhibitors rescued both MDM2 and H(2)O(2)-induced degradation of ARC and inhibited cardiomyocyte apoptosis. Dilated cardiomyopathic hearts from mice that have undergone transverse aortic banding have increased MDM2 levels associated with decreased ARC levels. We conclude that MDM2 is a critical regulator of ARC levels in cardiomyocytes. Prevention of MDM2-induced degradation of ARC represents a potential therapeutic target to prevent cardiomyocyte apoptosis.

Smoking and wound healing problems in reduction mammaplasty: is the introduction of urine nicotine testing justified?

We sought to prove a significant relationship between cigarette smoking and wound healing problems in reduction mammaplasty patients, to show the effect of stopping smoking before the procedure, and to justify the implementation of urine nicotine testing preoperatively. One hundred and seventy-three consecutive patients aged 16 to 67 years underwent bilateral reduction mammaplasty in our institution over 26 months. Patients were advised to stop smoking at least 4 weeks prior to surgery. Records were reviewed and smoking habits reconfirmed via telephone. Wound problems were registered when intervention was necessary. Smokers made up 38.5% of the cases. Wound healing problems showed statistical significance (P < 0.05) between smokers (55.4%) and nonsmokers (33.7%). More than 75% of smokers admitted denying smoking within 4 weeks of surgery. Trend analysis revealed a significant association of wound healing problems for those who stopped longer than 4 weeks (33.3%), those who stopped less than 4 weeks (52.6%), and those who persisted until the operation (67.7%). Smoking increased wound healing problems after bilateral reduction mammaplasty. The introduction of compulsory urine nicotine testing at the preadmission clinic and prior to the operation will provide objective verification of patients' smoking history, minimize morbidity, and enable healthcare cost savings.