Prospective study of skin surgery in smokers vs. nonsmokers.

BACKGROUND: Smoking may increase complications following minor surgery leading many clinicians to urge patients to refrain from smoking before and after surgery. OBJECTIVE: To study the association between smoking and complications following skin surgery. METHODS: In a 5-year prospective observational study 7224 lesions were excised on 4197 patients. Patients were not instructed regarding smoking. All complications were recorded. RESULTS: A total of 439 smokers (10.5%) underwent 646 procedures (9%), 3758 nonsmokers (89.5%) underwent 6578 procedures (91%). Smokers were younger (55 +/- 16 years) than nonsmokers (66 +/- 17 years) (P < 0.001). Infection incidence was not significantly different, 1.9% (12/646) in smokers compared with 2.2% (146/6578) in nonsmokers (P = 0.55). There were two bleeds with smokers (0.3%) vs. 50 in nonsmokers (0.8%) (P = 0.2). The incidence of wound dehiscence in nonsmokers (three) was not different from nonsmokers (21) (P = 0.54). However, the incidence of scar contour distortion in smokers (three) was greater than in nonsmokers (two) (odds ratio 15.3; 95% confidence interval 2.5-92). Total complication incidence was similar, 3.6% in smokers vs. 4.0% in nonsmokers (P = 0.58). Out of 2371 flaps there were 14 (0.6%) cases of end-flap necrosis but smokers were not at increased risk. The case-control analysis compared each smoker with two nonsmokers matched for age, sex, postal code and outdoor occupational exposure. This again demonstrated no difference in infection, scar complication, bleed, dehiscence, end-flap necrosis or total complication incidence. CONCLUSIONS: Smokers and nonsmokers suffer skin surgery complications similarly. The increased risk of contour distortion identified was difficult to interpret. Advice to cease smoking in the short term to improve outcomes with skin cancer surgery is not supported by these data.

Bleeding complications in skin cancer surgery are associated with warfarin but not aspirin therapy.

BACKGROUND: The aim was to identify risk factors for postoperative bleeding following skin cancer surgery. METHODS: This was a prospective study of 5950 skin lesions excised in 2394 patients. No patient stopped taking aspirin or warfarin unless the international normalized ratio (INR) exceeded 3.0. RESULTS: The rate of postoperative bleeding was 0.7 per cent overall and 2.5 per cent in the 320 patients taking warfarin. The rate of bleeding was 1.0 per cent for skin flap repairs, 0.4 per cent for simple excision and closure, and 5.0 per cent for skin grafts. Diabetic patients and smokers were not at increased risk of bleeding. There were four independent factors for bleeding: age 67 years or older (odds ratio (OR) 4.7 (95 per cent confidence interval 1.8 to 12.2); P = 0.002), warfarin therapy (OR 2.9 (1.4 to 6.3); P = 0.006), surgery on or around the ear (OR 2.6 (1.2 to 5.7); P = 0.012) and closure with a skin flap or graft (OR 2.7 (1.4 to 5.3); P = 0.004). Aspirin therapy was not an independent risk factor for bleeding. CONCLUSION: Most postoperative bleeds were inconvenient but not life threatening, unlike the potential risk of thromboembolism after stopping warfarin or aspirin. There was no case for discontinuing aspirin before skin surgery, but the INR should be monitored in patients taking warfarin.

Randomized clinical trial of the effect of applying ointment to surgical wounds before occlusive dressing.

BACKGROUND: A blinded randomized clinical trial was undertaken to evaluate the effect of applying ointment to a wound before occlusive dressing, in comparison with no ointment or sterile paraffin. METHODS: Some 778 patients with 1801 surgical wounds following excision of skin lesions were enrolled in the trial. No ointment was placed on 510 sutured wounds of 247 patients, paraffin ointment was put on 729 wounds (269 patients) and mupirocin ointment on 562 wounds (262 patients). Wound infection, scar, haemorrhage, dehiscence and other complications were assessed at suture removal. At 6-9 months after surgery, patients were surveyed to assess the wounds, with a response rate of 74.0 per cent. RESULTS: There were no significant differences in outcome for all endpoints evaluated. The infection rate was 1.4 per cent with no ointment, 1.6 per cent for paraffin and 2.3 per cent for mupirocin (P = 0.490). Total complication rates were 3.5, 4.7 and 4.8 per cent for no ointment, paraffin and mupirocin respectively (P = 0.590). Some 10.9, 10.3 and 8.2 per cent of patients respectively had a neutral or negative perception of their wounds at 6-9 months after surgery (P = 0.650). There was no difference in postoperative pain, degree of inconvenience or overall level of satisfaction with treatment. CONCLUSION: Putting ointment on a surgical wound before occlusive dressing does not benefit the patient. In view of the risk of antibiotic resistance, mupirocin ointment is not indicated for clean surgical wounds.

Post-transcriptional regulation of Xwnt-8 expression is required for normal myogenesis during vertebrate embryonic development.

The Xenopus Wnt-8 gene is transiently expressed in ventral and lateral mesoderm during gastrulation and plays a critical role in patterning these tissues. In the current study, we show that the spatial and temporal pattern of expression of endogenous Xwnt-8 is regulated, in part, at a post-transcriptional level. We have identified a novel sequence element in the 3' untranslated region of the Xwnt-8 RNA that controls the polyadenylation status of reporter and endogenous Xwnt-8 RNAs, directs rapid RNA degradation beginning precisely at the early gastrula stage, and represses translation of transcripts throughout development. Expression of endogenous Xwnt-8 is normally downregulated within lateral (presomitic) mesoderm following gastrulation. We demonstrate that rapid degradation of Xwnt-8 transcripts, mediated by these regulatory elements in the 3' untranslated region, is essential to this process and that downregulation is required to prevent overcommitment of somitic cells to a myogenic fate. These studies demonstrate a role for post-transcriptional regulation of zygotic gene expression in vertebrate embryonic patterning.

Temporal modulation of cytokine expression following focal cerebral ischemia in mice.

There is increasing evidence that the inflammatory response plays an important role in CNS ischemia. The murine model of focal ischemia, however, remains incompletely characterized. In this study we examined expression of several cytokines and the vascular adhesion molecule E-selectin, in order to characterize the molecular events following stroke in the C57BL/6J mouse. Using a multi-probe RNAse protection assay (RPA), mRNA for 19 cytokines was analyzed following permanent and transient occlusion of the middle cerebral artery in mice. In addition, samples from the same mice were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate E-selectin mRNA expression levels. Several cytokine mRNAs showed a similar expression pattern in both permanent and transient CNS ischemia while others showed a temporal expression pattern that was dependent on the type of stroke. For both models, mRNA levels of TNFalpha rose early (4 h) followed by IL-6 (10-18 h) and a comparatively late increase (96 h) in TGFbeta1. IL-1alpha, IL-1beta and IL-1ra levels showed a model dependent shift in temporal expression. Reperfusion appeared to delay the induction of these cytokines. Temporal changes in cytokine mRNA expression in the mouse CNS occur following ischemic damage. Our findings demonstrate the utility and power of multi-probe RPA for evaluation of changes in cytokine mRNA levels. Moreover, this study is, to our knowledge the first to show temporal changes in cytokine mRNA in mouse cerebral ischemia, forming a basis for further exploration of the roles of these cytokines in modulating ischemic neuronal damage in this model.

Monofilament intraluminal middle cerebral artery occlusion in the mouse.

The rat middle cerebral artery (MCA) occlusion model with an intraluminal filament is well characterized with a two hour period of occlusion in widespread use. The recent availability of transgenic animals has led to an interest in adapting the MCA model in the mouse. To date the model has not been well characterized in the mouse. We performed the present study to compare different durations of MCA occlusion and to validate new functional assessments in this model. The MCA occlusion model (5-0 filament) was used. Swiss-Webster mice, 24-44 g, were randomly assigned to four groups: one hour of occlusion; two hours of occlusion; three hours of occlusion; or permanent occlusion. At 48 hours post-ischemia, the animals were rated on three neurologic function scales, and then the brains were removed for lesion size determination. Overall, there was a significant difference in lesion volume (p < 0.001) between the groups. In the permanent group of mice, the average lesion volume was 78.41 +/- 17.47 mm (n = 12); two and three hours of ischemia produced 51.29 +/- 29.82 mm3 (n = 11) and 54.85 mm3 (n = 13), respectively, significantly different than the one hour group 14.84 +/- 31.34 mm3 (n = 11). All three functional scoring systems found significant overall differences between the four groups with our detailed General and Focal scores producing more robust between group treatment differences and showing correlation coefficients of r = 0.766 and r = 0.788, respectively to infarct volume. The MCA filament occlusion model can be successfully adapted in the mouse with either two or three hour occlusions producing reliable infarcts. New functional scoring systems unique to the mouse appear to add additional information.