Localized melanoma in older patients, the impact of increasing age and comorbid medical conditions.

BACKGROUND: Elderly patients experience a different spectrum of disease and poorer outcomes than younger patients. This study investigated the impact of age and medical comorbidities on the management and outcome of patients ≥65 years. METHODS: A retrospective review of all patients ≥65 years (481 patients with 525 primary melanomas) presenting with AJCC clinical stage I-II melanoma to an Australian cancer centre between 2000 and 2008. RESULT: The median age was 74 years (65-94) with a male predominance (313 males, 65.0%) and median tumour thickness of 1.90 mm (IQR = 0.40-2.90, T1 = 33%, T2 = 20%, T3 = 24%, T4 = 23%). Inadequate surgical margins of excision (<10 mm) were common in older patients independent of site, thickness and ulceration (OR = 1.04, 95%CI = 1.00-1.07, p = 0.038). Inadequate excision margins were strongly associated with time to local recurrence, independent of age, thickness, ulceration and mitotic rate (HR = 3.00, 95%CI = 1.49-6.03, p = 0.0021), but not time to progression (p = 0.10) or disease specific survival (DSS, p = 0.27). Overall survival (OS) was strongly related to increasing age (HR = 1.04, 95%CI = 1.01-1.07, p = 0.015) and comorbid medical conditions (HR = 1.26, 95%CI = 1.12-1.42, p < 0.001), as assessed by the Charlson comorbidity index (CCI). DSS was significantly related to CCI (HR = 1.20, 95%CI = 1.01-1.42, p = 0.041) and not age (p = 0.46), when adjusting for thickness, ulceration and mitotic rate on multivariate analysis. CONCLUSION: Older patients present with poor prognosis melanomas yet are less likely to receive adequate surgical excision margins resulting in higher rates of local recurrence. In melanoma patients ≥65 years, the increasing number of medical comorbidities explains much of the age related variations in OS and DSS and should be considered when planning treatment.

Does the abundance of girellids and kyphosids correlate with cover of the palatable green algae, Ulva spp.? A test on temperate rocky intertidal reefs.

This study assessed whether the abundance of girellids and kyphosids was related to cover of the palatable green algae, Ulva australis and Ulva compressa, on rocky intertidal reefs in Jervis Bay, New South Wales, Australia. No relationship was found between Ulva spp. cover and abundance of Girella tricuspidata, Girella elevata and Kyphosus sydneyanus during a period of relatively low Ulva spp. cover (i.e. February 2011 to March 2011), but during a period of significantly higher Ulva spp. cover (i.e. October 2011 to November 2011) there was a strong correlation between Ulva spp. cover and G. tricuspidata abundance. Spatial analysis indicated that the abundance of G. tricuspidata was consistent across time, suggesting G. tricuspidata were not moving between reefs in response to variation in Ulva spp. cover between periods but rather that large schools of G. tricuspidata resided on reefs that had relatively higher Ulva spp. cover at certain times of the year.

Fibrous ankylosis after distraction osteogenesis of a costochondral neomandible in a patient with grade III hemifacial microsomia.

Distraction osteogenesis has recently become a mainstay for treatment of craniofacial syndromes with mandibular hypoplasia. This article presents the difficult case of a patient with a previous costochondral rib graft who underwent mandibular distraction and developed a fibrous pseudoarthrosis at the distraction site. This was attributed in part to an associated temporomandibular joint ankylosis. Resorption of the pseudoarthrosis occurred once the distractor was removed. It appears that distraction osteogenesis of a mandible with an ankylosed temporomandibular joint can result in healing with a fibrous union, presumably because of movement at the distraction site when masticating. This can result in a pseudo "temporomandibular joint" at the distraction site. A temporomandibular joint arthroplasty was performed, followed by repeat distraction. We conclude that if there is an ankylosed temporomandibular joint or a stiff temporomandibular joint that may ankylose during the course of the distraction process, then a temporomandibular joint arthroplasty should be performed before or at the time the distractor is placed.

The screening pelvic radiograph in pediatric trauma.

BACKGROUND: Pelvic radiographs are routinely obtained in adult trauma to optimise early management. In adults, pelvic fractures are associated with high early transfusion requirement, high injury severity scores and an increased incidence of other abdominal and thoracic injuries. It is unclear whether this holds true in children. OBJECTIVE: To determine whether the screening pelvic radiograph is necessary in paediatric trauma. MATERIALS AND METHODS: The notes of all patients who presented after trauma to the Starship Children's Hospital and were triaged to the resuscitation room during 1997 were reviewed. Results of initial radiography were obtained and correlated with later imaging. RESULTS: Our review of 444 injured children seen over a period of 1 year revealed that of 347 children who had screening pelvic radiographs, only 1 had a pelvic fracture. The fracture in this child was clinically apparent and required no specific treatment. CONCLUSIONS: The presence of a pelvic fracture is rare in injured children. By omitting screening pelvic radiographs there are potential benefits, including reduced radiation exposure to children and cost savings. Uninterpretable or abnormal clinical examination or haematuria requires further investigation, but routine screening for pelvic fracture is unnecessary.

The use of temporary laparoscopic loop ileostomy in lumbosacral burns.

The technique of laparoscopic formation of loop ileostomies has been previously described for use in a variety of conditions. We present this as an option for faecal diversion in severe burns involving the back and buttock region and describe its use in two cases. Faecal diversion allows for easier wound care and nursing. Intra-abdominal assessment of these very sick patients can also be performed simultaneously. The technique is relatively simple, readily available and associated with minimal morbidity. Furthermore, this technique minimises interference with the abdominal wall as a donor site for skin grafts.

Piecing together the biggest puzzle of all.

In this month's essay, the last in the Pathways of Discovery series, Martin J. Rees celebrates the way astronomers and cosmologists have systematically uncovered the biography of the universe. Rife with neutron stars, black holes, and multiple universes that emerge from quantum fluctuation, it's a story as grand as it is strange.

The universe at z > 5: when and how did the "dark age" end?

This paper considers how the first subgalactic structures produced the UV radiation that ionized the intergalactic medium before z = 5 and the "feedback" effects of the UV radiation on structure formation. The first "pregalaxies" may eventually be detectable by their direct UV emission, with characteristic spectral features at Lyman alpha; high-z supernovae may also be detectable. Other probes of the intergalactic medium beyond z = 5, and of the epochs of reheating and reionization, are discussed, along with possible links between the diffusion of pregalactic metals and the origin of magnetic fields.

Causes and effects of the first quasars.

The light we observe from the most distant known quasars set out when the Universe was about 200 times denser than it is now and less than one-tenth of its present age. The existence of these objects implies that galaxy formation had already, at that early epoch, proceeded to the stage when massive (>10(8)M[symbol, see text]) objects had accumulated in the centers of at least some young galaxies. A specific model is presented to show that the evolution and luminosity function of quasars are compatible with the cold dark matter cosmogony. Most big galaxies probably passed through a quasar phase; the remnant black holes in nearby galaxies may reveal themselves via the flares that occur whenever a star passes too close to them and gets tidally disrupted. The rich absorption spectra of quasars serve as a probe of the intervening medium. The gas responsible for the Lyman alpha absorption lines may be due to primordial gas gravitationally confined in minihalos of dark matter--shallow potential wells whose evolution and relation to dwarf galaxies are briefly discussed. The patchy heat input into the intergalactic medium from early quasars could modulate the environment in which galaxies form, leading to large-scale spatial correlations in the galaxy distribution. This review concludes with general comments on the prospects for a fully quantitative understanding of galaxy formation.

Invasive naevus of Ota.

A slowly invasive naevus of Ota was followed for 50 yrs. During this time multiple biopsies were considered to be benign cellular blue naevus. The left globe, orbit, frontal bone and meninges were excised to achieve clearance.

CONCLUDING SUMMARY.

We have heard a wide-ranging set of talks on cosmology and high energy astrophysics at this conference. All I can really do in this short talk is to present my subjective impression of an arbitrary selection of highlights.

"Dead quasars" in nearby galaxies?

The nuclei of some galaxies undergo violent activity, quasars being the most extreme instances of this phenomenon. Such activity is probably short-lived compared to galactic lifetimes, and was most prevalent when the universe was only about one-fifth of its present age. A massive black hole seems the inevitable end point of such activity, and dead quasars should greatly outnumber active ones. In recent years, studies of stellar motions in the cores of several nearby galaxies indicate the presence of central dark masses which could be black holes. This article discusses how such evidence might be corroborated, and the potential implications for our understanding of active galaxies and black holes.

The effect of two novel analogues of antimycin A on oxygen consumption and survival of filarial nematodes in vitro.

The effects of two novel analogues of antimycin A (BWA466C and BWA728C) on filarial oxygen consumption, energy generation and survival were investigated in vitro. For comparison, incubations were performed with a range of mitochondrial respiration inhibitors. All compounds tested (rotenone, antimycin A, KCN, oligomycin, CCCP, rafoxanide, BWA466C and BWA728C) inhibited oxygen uptake. The two analogues were less potent than antimycin A at impairing respiration of either filariae or beef heart submitochondrial particles. However, the two compounds affected motility and were lethal in vitro. Although the analogues affected oxygen uptake similarly to antimycin A itself, the levels of ATP were significantly lower than those noted in the presence of antimycin A. Glucose consumption and lactate output were markedly reduced by BWA466C and BWA728C. Glucose transport (measured as 2-deoxy-[2,6-3H]glucose) was reduced after treatment with BWA728C. It is likely that a combination of the effects on glucose transport and inhibition of oxidative pathways of carbohydrate metabolism may lead to worm death in vitro.

The further application of MTT-formazan colorimetry to studies on filarial worm viability.

Experiments have confirmed that MTT-formazan colorimetry in its simplest form (incubation of intact worms with MTT and direct visualisation of any formazan formed) can be readily applied to several species of filariae including Onchocerca volvulus. Data is presented which will assist the development of quantitative MTT reduction viability tests for a selection of the smaller filarial species. Assays of pieces of Onchocerca gutturosa and O. volvulus females have led us to tentatively conclude that the tips of filariae, particularly the anterior ends, may well be metabolically the most active part of the worm. Selective sampling of these regions for Onchocerca might therefore be a useful indicator for the viability of the parasite. An example of how MTT-formazan colorimetry has been applied to yield additional data to support motility observations on the in vitro survival of male O. gutturosa is also given. The in vitro timecourse of worm death caused by 10 microM CGP 20376 on Acanthocheilonema viteae females has been examined by MTT reduction and compared with 6 other non-subjective parameters. The results suggests that the parameters examined could be divided into two groups according to the time taken for CGP 20376 to cause 50% inhibition (t50) of the parameter. Fast response parameters had t50's between 1 and 6 h (motility indices, 14CO2 evolution, adenine uptake and leucine uptake), they are more sensitive measures of viability and indicate possible worm damage which may or may not be reversible. Slow response parameters had t50's between 34 and 48.5 h (lactate output, MTT reduction and adenine leakage), and are probably linked with severe degenerative changes and are indicative of worm death.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiorespirometric detection of macrofilaricidal activity in vitro.

An in vitro method for studying radiorespiration has been adapted to single macrofilariae. Using this method viable (but not heat-killed) Dipetalonema viteae and Onchocera gibsoni macrofilariae evolved measurable amounts of 14CO2 from L-[U-14C]glutamine. Nonlinear and less uniform rates of 14CO2 evolution were demonstrated with D-[U-14C]glucose, [1-14C]acetate and [1-14C]octanoate. These findings led us to develop an in vitro screen in which inhibition of 14CO2 evolution from L-[U-14C]glutamine was used as a parameter for gauging macrofilaricidal activity. Using this screen we have examined the activity of 17 'so-called' antifilarial standards and found a greater degree of sensitivity than shown by other biochemical criteria. Other data obtained suggest a role for radiorespirometry in determining the viability of fragments of Onchocerca tissue.

Colorimetric quantitation of filarial viability.

A simple three-step colorimetric assay based on the tetrazolium salt MTT (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) has been developed for quantifying filarial viability. Living (but not dead) filariae take up MTT and rapidly reduce it to formazan, so staining themselves dark blue. This colour change which is easily seen provides a rapid qualitative test for filarial viability. Quantitative data can be obtained by solubilizing formazan out of the worm with DMSO and measuring the absorbance of the resulting solution at 510 nm. To date the technique has been demonstrated in several species of filariae including Onchocerca volvulus. MTT reduction is thought to be selective for NADH-dependent dehydrogenase activity in viable worms. The reaction occurs readily in all developmental stages of Dipetalonema viteae including fragments of filarial tissue. Enzyme activity in viable intact D. viteae appears to be primarily associated with the hypodermis/muscle cells, with minimal formazan formation in the gut and reproductive tracts. The application of this MTT assay as a parameter for quantifying in vitro drugs effects is described. Assay procedures have been developed and optimized with D. viteae and Brugia pahangi for the assessment of effects of macrofilariae and microfilarial release, and the activity of a range of antifilarial standards reported. Several potential applications of the technique to studies on filarial biology are discussed.

The application of biochemical criteria to the assessment of macrofilarial viability.

Previous attempts to assess nematode viability have been critically reviewed and the need to apply more objective biochemical criteria emphasized. The practicalities of assay development have been discussed with regard to sensitivity, selectivity and methodological considerations. The biochemical basis and assay methology for six assays (adenine leakage, adenine uptake, leucine uptake, 14CO2 evolution, lactate output and MTT reduction) that we have recently evaluated are detailed. The viability of Acanthocheilonema viteae females exposed for 120 h in vitro to 17 standard compounds (at 10 microM) has been assessed using these six assays and compared relative to motility indices from the micromotility meter. It was concluded that, despite the slightly superior sensitivity of the 14CO2 evolution assay, the MTT reduction method was most suitable for field use due to its technical and practical simplicity, and its applicability to fragments of onchocercal tissue. It was suggested that, in the absence of a better in vitro assay, the feasability of using MTT reduction together with histology should be assessed in a validation exercise with Onchocerca gibsoni.

Leakage of incorporated radiolabelled adenine--a marker for drug-induced damage of macrofilariae in vitro.

An objective in vitro assay has been developed for quantifying drug-induced damage in Dipetalonema viteae macrofilariae. The method involves radiolabelling the worms ATP pool by incubating macrofilariae with [U-14C]-adenine. As determined by HPLC 72% of the incorporated label was in ATP, 15% in ADP and about 4% in each of NAD and AMP. Macrofilariae labelled with [U-14C]-adenine show a linear efflux of [14C]-label amounting to 21.3% of the total incorporation (mainly as uncharged catabolites) over a time course of 120 h in vitro incubation. When prelabelled worms were exposed to compounds exerting macrofilaricidal effects in vitro a marked stimulation in the leakage of [14C]-label from the worms was noted. The [14C]-label leakage appears to be linked with membrane (or cuticle) damage and the reduction of macrofilarial ATP levels. Determination of the amount of [14C]-label remaining in drug-treated worms relative to appropriate control provides a simple, sensitive and quantitative measure of drug-induced damage in macrofilariae (including Onchocerca). The method has been used to describe the macrofilaricidal activity of a wide range of antifilarial standards, membrane disruptive agents, respiratory inhibitors, fasciolicides and anti-cestode compounds.

Immediate amputation stump coverage with forearm free flaps from the same limb.

When the traumatic amputation level or the degree of damage to the arm or forearm does not justify reimplantation of the severed part there may be sufficient undamaged skin to be used as a free flap to resurface the arm or the stump. Stump length or the elbow joint may thus be preserved and more durable skin cover for the fitting of a prosthesis may be obtained. A "spare-parts" forearm free flap may be raised on the radial or ulnar vessels or both. Three cases are reported.

Economical use of the "groin" flap: then and now.

It is uncommon to be able to use the same flap to resurface a defect of the hand and another extremity of the body. Two cases are presented. In one, the hand and neck and in the other, the hand and foot were resurfaced from the same flap. In the former a tubed pedicle flap was used and in the latter, part of a groin flap was transferred as a free flap.

A simplified lead oxide cadaver injection technique.

A simple, inexpensive injectable substance is reported for analysis of the arterial circulation in fresh human or animal cadavers. The technique is a modification of that reported by Salmon in 1936 and utilizes lead oxide and gelatin. This combination is highly radiopaque; it perfuses the small radicles of the vascular tree and sets to a firm rubbery consistency to fascilitate dissection.