Modified muscle sparing latissimus dorsi with implant for total breast reconstruction - extending the boundaries.

UNLABELLED: Refinements in breast reconstruction have led to a better understanding of aesthetics and a reduction of donor morbidity. The muscle sparing latissimus dorsi (MS-LD) is a step towards this. It has previously been described for reconstruction in partial mastectomy defects. We describe a modification of the MS-LD that permits total breast reconstruction. MATERIAL AND METHODS: Between June 2006 and October 2008, 22 MS-LD flaps were used in 18 patients. A tiny lateral muscle segment containing the descending branch of the thoracodorsal artery along with its thoracodorsal artery perforators (TDAPs) was used as a pedicle to carry a large skin and fascial flap in all cases. The fascial component permitted complete coverage of the implant in a pre-pectoral pocket. Innervation and vascularity to the remaining muscle was preserved. Postoperatively, DASH questionnaires were sent out to the patients to objectively assess shoulder morbidity. RESULTS: Skin dimensions ranged from 16x8 centimetres (cm) to 25x10cm. Follow up ranged from 3 to 30 months. Four minor and three major complications occurred. There was no total flap loss and no seromas. We achieved high patient satisfaction regarding the aesthetic outcome and with preservation of functional latissimus dorsi (LD) muscle. CONCLUSION: The muscle sparing technique is useful in a selected group of highly active post-mastectomy patients. It is quicker and more reliable(1) than a pure perforator flap approach and can be used to reconstruct the entire breast, preserving the remaining functional muscle for possible backup option in cases of salvage.

Frostbite following use of a commercially available cryotherapy device for the removal of viral warts.

Warts are a common skin complaint in childhood. We describe 3 unusual cases in which inadvertent tissue injury was caused during the treatment of viral warts by a commercially available cryotherapy device. In each case there was a failure to follow the instructions provided correctly. If such devices are to remain available for public use we feel changes should be implemented to reduce the risk of such injuries occurring again in the future. Alternatively, cryotherapy as a treatment modality should remain in the realm of the trained health care professional.

Selective antagonism of native and cloned kainate and NMDA receptors by polyamine-containing toxins.

Antagonism of rat excitatory amino acid receptors by a synthetic analog [philanthotoxin-343 (PhTX-343)] of a polyamine amide, wasp toxin (philanthotoxin-433) and a structurally related spider toxin, argiotoxin-636 (ArgTX-636), was examined in Xenopus oocytes injected with rat brain RNA or RNA transcribed from the excitatory amino acid receptor clones GluR1, GluR2 and NMDAR1. Antagonism of both kainate- and N-methyl-D-aspartate (NMDA)-elicited responses by PhTX-343 and ArgTX-636 was reversible, noncompetitive and partly voltage-dependent. Dose-inhibition curves were constructed using EC50 concentrations of kainate (100 microM) and N-methyl-D-aspartate (33 microM) in the presence of variable concentrations of ArgTX-636 and PhTX-343. In oocytes injected with rat brain RNA, IC50s for antagonism of kainate-induced currents were similar, i.e., 0.07 microM and 0.12 microM for ArgTX-636 and PhTX-343, respectively, whereas IC50s for antagonism of NMDA-induced currents were dissimilar, i.e., 0.04 microM for ArgTX-636 and 2.5 microM for PhTX-343. In oocytes expressing NMDAR1, IC50s were similar to those for the antagonism of NMDA-induced currents of oocytes injected with rat brain RNA. PhTX-343 and ArgTX-636 were more or less equally potent (IC50s were 2.8 microM and 3.4 microM, respectively) antagonists of the response of GluR1 to 100 microM kainate. However, GluR1 was approximately 50 times less sensitive to the toxins than non-N-methyl-D-aspartate receptors expressed in oocytes injected with rat brain RNA. Receptors co-expressed from GluR1 + GluR2 were virtually insensitive to PhTX-343 (IC50 = 270 microM) and to ArgTX-343 (IC50 approximately 300 microM).

Are chimeric kainate/N-methyl-D-aspartate receptors expressed in Xenopus oocytes from mammalian and amphibian RNA?

The Xenopus oocyte expression system has been used to test for the existence in rat and Xenopus central nervous systems (CNS) of excitatory amino acid receptors (EAAR) that show sensitivity to both N-methyl-D-aspartate (NMDA) and L-kainate. Two to 15 days after injection of oocytes with rat brain poly(A+) RNA (or total RNA) and Xenopus CNS poly(A+) RNA, voltage-clamped oocytes were tested for EAAR expression by exposure to various excitatory amino acids (EAA). Responses to coapplication of NMDA and/or kainate were less than the sum of those obtained during application of each of these two EAA alone. In both cases, the antagonism was noncompetitive, although at millimolar concentrations, competitive antagonism was also observed. The extent of noncompetitive antagonism by NMDA of the response to kainate was proportional to an oocyte's sensitivity to NMDA. Oocytes injected with mRNA transcribed from the GluR1 clone encoding a rat non-NMDA receptor subunit did not respond to NMDA, and antagonism of the response to kainate occurred only with millimolar concentrations of NMDA and was competitive. Various explanations for these results are discussed. One possibility is that Xenopus oocytes injected with these vertebrate CNS RNA express a subpopulation of receptors containing kainate-sensitive and NMDA-sensitive subunits in addition to NMDA receptors and non-NMDA receptors. This explanation is supported by the observation that the NMDA antagonists MK-801 and magnesium antagonize part of the current induced by kainate, but only when NMDA is present.

Philanthotoxin-343 blocks long-term potentiation in rat hippocampus.

The effects of extracellularly-applied synthetic philanthotoxin-343 (PhTX-343) on transmission and long-term potentiation (LTP) at Schaffer-collateral/commissural-CA1 synapses were investigated. PhTX-343 was ineffective in antagonizing CA1 field-EPSPs mediated by AMPA/kainate receptors. However, when a micromolar concentration of the toxin was present during tetanization, the induction of LTP was suppressed. In contrast, when PhTX-343 was applied either immediately after or long after tetanization no effect on LTP could be found. It appears that the synaptic, non-NMDA receptors of the CA1-region are insensitive to PhTX-343. Suppression of LTP induction could result from antagonism of postsynaptic NMDA receptors, but the results do not rule out other possibilities such as presynaptic block.

Arthropod toxins as leads for novel insecticides: an assessment of polyamine amides as glutamate antagonists.

In the search for new toxins, preferably with new sites of action, the polyamine amides represent a new class of compounds with potential as insecticides and as pharmaceutical agents due to their antagonism of ligand-gated cation channels. In particular, they are potent antagonists of the L-glutamate receptors of insect skeletal muscle. In this paper, we report on synthetic studies to produce hybrid analogues based upon the argiotoxin spider toxins and philanthotoxin-433 which is obtained from a solitary, parasitic wasp. We speculate upon possible modes and sites of action for these antagonists and we discuss their potential as insecticides and in the possible treatment of ischaemic damage. The synthesis and characterization of 4-hydroxyphenylpropanoylspermine is reported and the locust muscle biological assay is described. Using this pharmacological screen, structure-activity relationships have been determined in our laboratories. These are reviewed in the light of the current literature. Voltage clamp studies of the synthetic analogue philanthotoxin-343 and the effects of this polyamine amide on glutamate receptors expressed in Xenopus oocytes are outlined. In conclusion, a description of our current ideas and understanding of the many sites and modes of action of the polyamine amides, based both upon our own studies and also upon those recently reported, is presented.