Free tissue transfer in head and neck reconstruction: 100 consecutive cases.

OBJECTIVES: Free flap reconstruction of head and neck defects is a rapidly changing field. We present a case series in this field in which we critically assess our survival rates and complications, and we highlight specific technical variables that may be associated with improved outcomes. METHODOLOGY: This case series from a tertiary medical centre comprises 100 consecutive head and neck microvascular free flap reconstructions. Medical notes were reviewed specifically for indications, adjuvant and neoadjuvant chemoradiotherapy, complications, and outcome of the free flap. RESULTS: The overall flap survival rate was 99%, with a 6% return-to-theatre rate. Three cases had a general complication in the form of a non-flap compromising haematoma that necessitated a return to theatre for an evacuation. Specific microvascular anastomosis-related complication rate was 2% requiring salvage revision. One flap was lost due to infection. Of the 100 cases, 87% were fasciocutaneous free flaps, 7% were musculocutaneous, 5% were osseocutaneous, and one was a skin/cartilage free flap. With regard to indications for reconstruction, oncological resection accounted for 86% of cases; a total of 12% had mandibular bone involvement that required osseocutaneous reconstruction. CONCLUSIONS: We have highlighted specific technical steps we used that may have contributed to our positive results. Moreover, we encourage the use of standardised postoperative monitoring guidelines for all multidisciplinary surgical teams involved in head and neck patients; they facilitate communication and increase early detection of complications, permitting timely intervention, which may be critical for flap survival.

Two-stage hypospadias repair: audit in a district general hospital.

The number of techniques for hypospadias repair is testament to the challenges associated with this condition. In 1994, the senior author undertook an audit of his repairs using the van der Meulen [Plast. Reconstr. Surg. 59 (1977) 20615] technique and determined that the revision rate of 11% was unsatisfactory and the cosmetic result sub-optimal. He, therefore, retrained and began in 1995, using the two-stage technique popularised by Bracka [Br. J. Plast. Surg. 48 (1995) 345]. We undertook an audit of all corrections performed in the period from September 1995 to March 2002. The computer database in the main theatre suite was used to identify all patients on whom such a repair had been undertaken and those notes retrieved. Data was collected on a number of variables including age at operations, complications such as urinary tract infection and fistulae, and total number of corrective operations. One hundred and nineteen patients were identified, of which seven had no records available. Of the remaining 112, 81 were primary repairs, in whom the complication rate was 2.5% for stage I (graft loss) and 9.8% for stage II (fistula rate 7.4%, stenosis 1.2%, baggy urethra requiring reconstruction 1.2%). The remaining 31 patients were those with unsatisfactory single-stage repairs and in this group, graft loss was seen in three cases (10%). The fistula rate was 4/31 (12.9%) and the stenosis rate 2/31 (6.5%). These results compare favourably with a number of published series from surgeons who have super-specialised in this field. We conclude that the two-stage repair is a useful and reliable technique in the hands of a Plastic Surgeon who has a broader interest.

Manoeuvring a-head in plastic surgery.

Surgical training has undergone a rapid transformation over the last decade. One outcome of these changes is the interest that has been generated in the possibility of training surgical skills outside the operating theatre. We describe a cost-effective tool that may be used to improve surgical handling and improve surgical concepts in facial plastic surgery.

A study to evaluate primary dressings for the application of cultured keratinocytes.

Despite the recent improvements in cell culture and dermal regeneration methods, tissue engineering of skin has yet to receive widespread acceptance in the management of burn injuries. The reasons for this are complex and include not only the inherent costs of (particularly) setting up and running such a system but also the continuing difficulties in achieving successful engraftment of the neoepidermis. The latter has previously been addressed in a number of ways, including improving the recipient bed and using pre-confluent delivery systems to allow earlier application of cells to that wound bed. One area that has received little attention is that of the optimal wound dressing to use with this technology; the cells are very poorly attached at early time points, and, in this context, the traditional dressing of paraffin gauze has never been formally assessed in comparison with newer materials. Using a porcine acute wound chamber model, we performed a prospective randomised trial to assess four different wound dressings with reference to the amount of epidermal cover gained and the histological quality of the regenerated skin after 3 weeks. Out of the four materials tested, polyurethane foam (Allevyn) was superior histologically (although equal in take rate with paraffin gauze), whilst polythene sheet (Opsite) and silicone sheet were substantially inferior. We conclude that the traditional dressing used with this technology should be compared with polyurethane foam in a clinical trial. In the future, novel dressings should be formally tested against traditional methods before being adopted.

Trafficking-dependent and -independent pathways of neurotransmitter transporter regulation differentially involving p38 mitogen-activated protein kinase revealed in studies of insulin modulation of norepinephrine transport in SK-N-SH cells.

Presynaptic, cocaine- and antidepressant-sensitive norepinephrine (NE) transporters (NETs) dictate levels of extracellular NE after vesicular release. Recent studies suggest that G protein-coupled receptors linked to protein kinase C (PKC) down-regulate cell surface NET protein levels and diminish NE uptake capacity. We identified distinct phosphatidylinositol 3-OH kinase (PI3K)-linked pathways supporting basal and insulin-triggered NE transport in the human noradrenergic neuroblastoma, SK-N-SH. Acute (0-60 min) insulin treatments produced a time- and concentration-dependent stimulation of NE transport, resolved in kinetic studies as an enhancement of NE transport capacity (Vmax) without an alteration in NE Km. Basal and insulin-modulated NET activities were reduced by the tyrosine kinase inhibitor genistein and the PI3K inhibitors wortmannin and LY-294002, but not by the PKC inhibitor staurosporine. PI3K activation was found to support phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). However, basal and insulin-stimulated NET activities were differentiated by their reliance on p38 MAPK activation. Thus, the p38 MAPK inhibitor SB203580 and SB202190 abolished insulin activation of NE transport yet failed to impact basal NET activity. Moreover, p38 MAPK activation and insulin activation of NETs were found to be sensitive to external Ca2+ depletion, blockade of voltage-sensitive Ca2+ channels, and inhibition of protein phosphatase 2A. Effects of tyrosine kinase and PI3K inhibitors on basal NET uptake appear to arise from a loss of cell surface NET protein, whereas the p38 MAPK-dependent enhancement of NE transport occurs without a detectable enhancement of surface NET. Our findings establish two distinct pathways for regulation of NE uptake involving PI3K, one linked to transporter trafficking and a second linked to Ca2+-dependent, p38 MAPK phosphorylation that promotes activation of cell surface NETs.

RNA editing of the human serotonin 5-HT2C receptor alters receptor-mediated activation of G13 protein.

The recent completion of the human genome predicted the presence of only 30,000 genes, stressing the importance of mechanisms that increase molecular diversity at the post-transcriptional level. One such post-transcriptional event is RNA editing, which generates multiple protein isoforms from a single gene, often with profound functional consequences. The human serotonin 5-HT(2C) receptor undergoes RNA editing that creates multiple receptor isoforms. One consequence of RNA editing of cell surface receptors may be to alter the pattern of activation of heterotrimeric G-proteins and thereby shift preferred intracellular signaling pathways. We examined the ability of the nonedited 5-HT(2C) receptor isoform (INI) and two extensively edited isoforms, VSV and VGV, to interact with various G-protein alpha subunits. Two functional assays were utilized: the cell-based functional assay, Receptor Selection/Amplification Technology(TM), in which the pharmacological consequences of co-expression of 5HT(2C) receptor isoforms with G-protein alpha subunits in fibroblasts were studied, and 5HT(2C) receptor-mediated rearrangements of the actin cytoskeleton in stable cell lines. These studies revealed that the nonedited 5-HT(2C) receptor functionally couples to G(q) and G(13). In contrast, coupling to G(13) was not detected for the extensively edited 5-HT(2C) receptors. Thus, RNA editing represents a novel mechanism for regulating the pattern of activation of heterotrimeric G-proteins, molecular switches that control an enormous variety of biological processes.

Perniosis (chilblains) of the thigh: report of five cases, including four following river crossings.

Perniosis, or chilblains, are skin lesions that occur as an abnormal reaction to cold, damp environments. We describe five cases of perniosis affecting the thighs. Four of the five cases occurred after wading across mountain rivers. Histological changes of deep perniosis and panniculitis were seen in a skin biopsy from one of the cases. In each case there was marked pain and discomfort, and lesions resolved over more than 1 week.

Fascial feeder and perforator-based V-Y advancement flaps in the reconstruction of lower limb defects.

The principle of the V-Y advancement flap has been used since its first description by Blasius (1848) for reconstruction of smaller defects. We wish to describe V-Y advancement flaps, the design of which includes distinct perforator or fascial feeder vessels, which may originate from periosteum, muscle, cutaneous nerve or from large tendon sheaths. These flaps are planned in an oblique manner when there is a defect over the anterior, antero-lateral or antero-medial aspect, and in a vertical manner when there is a defect over the posterior aspect of the leg. The main advantage of this design is the ability to close the secondary defect primarily, allowing adequate cover of the defect, particularly in the pre-tibial region, without the unsightly divot left by a split skin graft in this area. When the flap includes branches of the long saphenous nerve on the medial aspect, superficial peroneal nerve laterally or sural nerve posteriorly it results in a sensate flap, giving protection in this vulnerable area, which has previously not been possible. We describe 40 cases where perforator-based V-Y advancement flaps have been used to cover large defects of the lower leg following excision of malignant skin lesions and in selected trauma cases that do not involve degloving injuries. This technique allows adequate soft tissue cover in the pre-tibial area and around the ankle with excellent aesthetic results. The planning, operative technique and the results with case presentations have been described.

RNA editing of the human serotonin 5-HT(2C) receptor delays agonist-stimulated calcium release.

RNA encoding the human 5-HT(2C) receptor undergoes adenosine-to-inosine RNA editing events at five positions in the putative second intracellular loop, with a corresponding reduction in receptor/G-protein coupling. Agonist-stimulated calcium release was examined in NIH-3T3 fibroblasts stably expressing the nonedited human INI (hINI) or the edited hVSV or hVGV variants. We hypothesized that different receptor isoforms would show altered dynamics of agonist-induced calcium release. The three isoforms showed a rightward shift in agonist concentration-response curves for eliciting calcium release (EC(50) values: hINI, 2.2 nM; hVSV, 15 nM; hVGV, 49 nM). Additionally, the hVGV receptor showed a blunted and delayed [Ca(2+)](i) peak compared with the hINI or hVSV receptor isoforms. These distinctions in agonist-induced [Ca(2+)](i) release imply that edited 5-HT(2C) receptors may produce distinct physiological responses within the central nervous system.

Temperature and duration of cardiopulmonary bypass influence transfusion requirements.

STUDY OBJECTIVE: To determine the influence of temperature and duration of cardiopulmonary bypass (CPB) on blood loss and transfusion requirements. DESIGN: Retrospective chart review. SETTING: Tertiary care, academic medical institution. MEASUREMENTS AND MAIN RESULTS: The charts of 378 patients who had undergone primary elective coronary artery bypass graft surgery were studied. Systemic perfusion of CPB had been conducted between 20 degrees C and 37 degrees C in all patients. Patient demographic, temperature during CPB, duration of CPB, blood loss, and transfusion requirements were all recorded. Hypothermic CPB patients had minor increases in requirements for transfusion of red blood cells (RBC; p = 0.01), fresh frozen plasma (FFP; p = 0.01), platelets (PLT; p = 0.003), and total (allogeneic and autologous) blood products (p < 0.001). Multivariate analysis revealed that decreased temperature after adjusting for duration was predictive of allogeneic (RBC, FFP, PLT, and cryoprecipitate) and total (allogeneic and autologous) transfusion requirements. The duration of CPB correlated with decreased temperature (r = -0.455; p < 0.0001). After adjusting for temperature, duration was only predictive of total (allogeneic and autologous) transfusion requirements. CONCLUSIONS: The institution of warm CPB has many ramifications for clinical practice. The hypothermic induced platelet dysfunction and increased duration associated with cold CPB may contribute to the minor increases in transfusion requirements. However, temperature appears to be a weak factor, neither supporting nor refuting the use of warm or cold CPB.