Tibiotalocalcaneal arthrodesis with a compressive retrograde nail: A retrospective study of 59 nails.

BACKGROUND: Tibiotalocalcaneal arthrodesis is an important salvage method for patients with complex hindfoot problems. This study reports the elective results of combined subtalar and ankle arthrodesis using one design of retrograde intramedullary compression nail. METHODS: Retrospective review identified 58 patients undergoing 59 tibiotalocalcaneal arthrodesis procedures. Mean follow up was 9.15 (3-36) months with average age 60.7 (22-89) years. A function and subjective patient satisfaction questionnaire was achieved in 89%. RESULTS: 53 patients (93%) achieved union at a mean time of 4.17 months. Four patients (8%) subjectively thought the procedure was of no benefit while 42 (84%) had an excellent or good result. The mean visual analogue scale (VAS) score for preoperative functional pain was 7.46 compared to 1.98 post-operatively (p<0.001). CONCLUSIONS: This device and technique offers an effective treatment of hindfoot pathology giving reliable compression and subsequent fusion with excellent patient satisfaction and pain relief. LEVEL OF EVIDENCE: IV case series.

A practical guide to the management of anophthalmia and microphthalmia.

Congenital anophthalmia and microphthalmia are rare developmental defects of the globe. They often arise in conjunction with other ocular defects such as coloboma and orbital cyst. They may also be part of more generalised syndromes, such as CHARGE syndrome. Anophthalmia, microphthalmia, and coloboma are likely to be caused by disturbances of the morphogenetic pathway that controls eye development, either as a result of primary genetic defect, or external gestational factors, including infection or drugs that can influence the smooth processes of morphogenesis. The ophthalmologist is often the primary carer for children with anophthalmia and microphthalmia, and as such can coordinate the multidisciplinary input needed to offer optimal care for these individuals, including vision and family support services. They are able to assess the vision and maximise the visual potential of the child and they can also ensure that the cosmetic and social impact of anophthalmia or microphthalmia is minimised by starting socket expansion or referring to a specialist oculoplastics and prosthetics unit. A coordinated approach with paediatrics is necessary to manage any associated conditions. Genetic diagnosis and investigations can greatly assist in providing a diagnosis and informed genetic counselling.

Polysulfone hollow fiber gas separation membranes filled with submicron particles.

Three different fillers, carbon black (CB), vapor grown carbon fibers (VGCF), and TiO(2), were incorporated into polysulfone spinning solutions with the intention of producing highly selective membranes with enhanced mechanical strength. The effect of filler presence on gas permeation characteristics, mechanical strength (bursting pressure), and morphology was investigated and compared to unfilled membranes. As well as studying filler types, the influence of CB filler concentration on membrane performance was also examined. For all filler types (at a concentration of 5%w/w), the pressure-normalized flux of O(2), N(2), and CH(4) was greater in the composite than in the unfilled membranes. The CO(2) pressure-normalized flux was only greater in the TiO(2) composite membranes. For CB and VGCF, the CO(2) pressure-normalized flux was reduced compared with unfilled membranes. Three CB concentrations were investigated (2, 5, and 10%w/w). For O(2), N(2), and CH(4), pressure-normalized flux peaked at 5%w/w CB. CO(2) exhibited the opposite trend, showing a minimum pressure-normalized flux at 5%w/w. Considering O(2)/N(2) and CO(2)/CH(4) gas pairs and the various filled membrane categories, only the O(2)/N(2) selectivity of the 2%w/w CB filled membranes was higher than that of the unfilled fibers-all other selectivities were lower. In terms of CB concentration, selectivity was a minimum at the intermediate concentration of 5%w/w. All the filled membrane types exhibited greater mechanical strength (bursting pressure) than unfilled fibers apart from the 5%w/w VGCF composites. The 2%w/w CB composites were the strongest. Electron microscopy showed no visible differences in general morphology between the various filled and unfilled membranes.

Magnetic resonance imaging assessment for unicompartmental knee replacement: a limited role.

The purpose of this study was to see if MRI has a role in pre-operative assessment of patients for unicompartmental knee replacement. Until now, surgeons have been unable to predict whether a patient is suitable until the operation itself when the anterior cruciate ligament is inspected. We found that 33% of patients with anteromedial osteoarthritis had a degenerate anterior cruciate ligament according to magnetic resonance imaging, compared to only 13% on surgical inspection. We conclude that MRI is too sensitive to changes of the anterior cruciate ligament to be of much practical value.

Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline transporter.

Cone snails use venom containing a cocktail of peptides ('conopeptides') to capture their prey. Many of these peptides also target mammalian receptors, often with exquisite selectivity. Here we report the discovery of two new classes of conopeptides. One class targets alpha1-adrenoceptors (rho-TIA from the fish-hunting Conus tulipa), and the second class targets the neuronal noradrenaline transporter (chi-MrIA and chi-MrIB from the mollusk-hunting C. marmoreus). rho-TIA and chi-MrIA selectively modulate these important membrane-bound proteins. Both peptides act as reversible non-competitive inhibitors and provide alternative avenues for the identification of inhibitor drugs.

Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes.

omega-Conotoxins selective for N-type calcium channels are useful in the management of severe pain. In an attempt to expand the therapeutic potential of this class, four new omega-conotoxins (CVIA-D) have been discovered in the venom of the piscivorous cone snail, Conus catus, using assay-guided fractionation and gene cloning. Compared with other omega-conotoxins, CVID has a novel loop 4 sequence and the highest selectivity for N-type over P/Q-type calcium channels in radioligand binding assays. CVIA-D also inhibited contractions of electrically stimulated rat vas deferens. In electrophysiological studies, omega-conotoxins CVID and MVIIA had similar potencies to inhibit current through central (alpha(1B-d)) and peripheral (alpha(1B-b)) splice variants of the rat N-type calcium channels when coexpressed with rat beta(3) in Xenopus oocytes. However, the potency of CVID and MVIIA increased when alpha(1B-d) and alpha(1B-b) were expressed in the absence of rat beta(3), an effect most pronounced for CVID at alpha(1B-d) (up to 540-fold) and least pronounced for MVIIA at alpha(1B-d) (3-fold). The novel selectivity of CVID may have therapeutic implications. (1)H NMR studies reveal that CVID possesses a combination of unique structural features, including two hydrogen bonds that stabilize loop 2 and place loop 2 proximal to loop 4, creating a globular surface that is rigid and well defined.

Exposure of primary orbital implants in postenucleation retinoblastoma patients.

PURPOSE: To determine significant factors influencing the exposure of primary orbital implants in patients with retinoblastoma. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred nine consecutive patients (110 sockets) who had undergone enucleation for retinoblastoma from January 1993 to December 1997. METHODS: Two patients with recurrence of orbital retinoblastoma were excluded from further analysis, leaving 107 patients (108 sockets). The parameters analyzed included the patient's age; gender; ocular diagnosis; surgeon; type, covering, and size of the implant; the use of chemotherapy or radiotherapy; and the timing of these treatments in relation to enucleation. Study patients were divided into two main groups: the "treated group"-patients who had undergone adjuvant external beam radiotherapy or chemotherapy, and the "untreated group"-patients had undergone enucleation with or without cryotherapy, laser thermotherapy, or brachytherapy to the index or fellow eye. The following additional parameters were noted in the patients with exposed implants: time to exposure from date of enucleation and treatment of exposure. MAIN OUTCOME MEASURE: Exposure of orbital implants. RESULTS: There were two exposures caused by orbital recurrence of retinoblastoma. The rate of nontumor recurrence exposure was 28% (30 of 108). The median time to exposure was 136 days (range, 1-630 days). There were 18 exposures (35%,18 of 51) in the treated group, with a 34% exposure rate (13 of 38) in the chemotherapy group. The exposure rate was 21% (12 of 57) in the untreated group. The rates of exposure according to implant were: Vicryl mesh-wrapped hydroxyapatite (2 of 18, 11%), Medpor (8 of 13, 53%), plain polymethylmethacrylate (PMMA) (4 of 50, 8%), Mersilene-wrapped PMMA (9 of 17, 53%) and Castroviejo (7 of 10, 70%). Eight of the exposures (27%) were managed conservatively; the remainder required surgical repair. CONCLUSIONS: Results suggested that implant type and covering (P = 0.000) had a highly significant effect on the rate of exposure in postenucleation retinoblastoma patients. There was no statistical evidence that age, gender, ocular diagnosis, surgeon, size of the implant, or radiotherapy had an effect on implant exposure. There was an increased rate of exposure in the chemotherapy group, although this did not achieve statistical significance (P = 0.058), but a detrimental effect could not be excluded.

Changing trends in cytomegalovirus retinitis with triple therapy.

PURPOSE: Cytomegalovirus retinitis (CMVR) has been the most common cause of visual loss in AIDS patients. We investigate whether the pattern of disease has changed since the introduction of triple therapy. METHODS: We reviewed the records of all patients with CMVR in one teaching hospital HIV unit over a 2 year period (n = 24). This included the opthalmic and systemic findings, HIV and CMV treatment, survival after diagnosis and CD4 results. RESULTS: There has been a marked decrease in the number of patients developing new CMVR: from 21 eyes (15 patients) to 4 eyes (4 patients) in two consecutive 12 month periods between January 1996 and December 1997, coinciding with the introduction of triple therapy in October 1996. Median survival has increased from 376 days in the deceased patients to 598 days in the survivors on triple therapy. Median time to CMVR relapse has lengthened from 79 to 179 days in the triple therapy cohort. The pattern of ocular morbidity in the 11 eyes of the 7 surviving patients is also changing, with no new zone 1 disease, and a marked rise in the incidence of uveitis, maculopathy and cataracts. CONCLUSION: Results suggest that triple therapy is associated with an increase in survival, a decrease in CMVR relapse and changes in ocular features. This transition has implications for current screening and treatment protocols.

Bound Tris confounds the identification of binding site residues in a paraquat single chain antibody.

We produced an anti-paraquat single chain antibody (scFv) to investigate its potential use in immunotherapy for paraquat poisoning. However, this scFv was expressed in an insoluble form and only displayed moderate binding affinity. An earlier examination of the pH dependence of antigen binding by the parent paraquat-specific mAb (7D7-3) suggested that the electrostatic effects of a tyrosine residue were important. The aims of the current study were to obtain expression of a soluble scFv (D10) and to increase its binding affinity. The former was achieved by expression in a phagemid vector. Site-directed mutagenesis of tyrosine residues in CDR H3 did not result in improved affinity for paraquat, suggesting that the original pH dependence required re-examination. Nuclear magnetic resonance studies of 7D7-3 Fab revealed that the original observation of the pH-dependent paraquat binding with a mid-point of approximately pH 8.9 was due to tightly bound Tris. It appears that as Tris is titrated to a neutral species the energetically unfavourable juxtaposition of its positive charge with that of paraquat is reduced. These findings have broad implications in the interpretation of the pH or salt dependence of any antibody-antigen interaction which should be made cautiously and with regard to the possible interference of buffer components introduced during the preparation of the antibody.

Amezinium and debrisoquine are substrates of uptake1 and potent inhibitors of monoamine oxidase in perfused lungs of rats.

Previous studies have resulted in the classification of amezinium as a selective inhibitor of neuronal monoamine oxidase (MAO), because it is a much more potent MAO inhibitor in intact tissues, in which it is accumulated in noradrenergic neurones by uptake1, than in tissue homogenates. In the present study, the effects of amezinium on the deamination of noradrenaline were investigated in intact lungs of rats, since the pulmonary endothelial cells are a site where the catecholamine transporter is non-neuronal uptake1. In addition, another drug that is both a substrate of uptake1 and a MAO inhibitor, debrisoquine, was investigated in the study. The first aim of the study was to show whether amezinium and debrisoquine are substrates of uptake1 in rat lungs. After loading of isolated perfused lungs with 3H-noradrenaline (MAO and catechol-O-methyltransferase (COMT) inhibited), the efflux of 3H-noradrenaline was measured for 30 min. When 1 mumol/l amezinium or 15 mumol/l debrisoquine was added for the last 15 min of efflux, there was a rapid and marked increase in the fractional rate of loss of 3H-noradrenaline, which was reduced by about 70% when 1 mumol/l desipramine was present throughout the efflux period. These results showed that both drugs were substrates for uptake1 in rat lungs. In lungs perfused with 1 nmol/l 3H-noradrenaline (COMT inhibited), 10, 30 and 300 nmol/l amezinium caused 58%, 76% and 74% inhibition of noradrenaline deamination, respectively, and 30, 300 and 3000 nmol/l debrisoquine caused 56%, 89% and 96% inhibition of noradrenaline deamination, respectively. When MAO-B was also inhibited, 10 nmol/l amezinium caused 84% inhibition of the deamination of noradrenaline by MAO-A in the lungs. In contrast, in hearts perfused with 10 nmol/l 3H-noradrenaline under conditions where the amine was accumulated by uptake2 (COMT, uptake1 and vesicular transport inhibited), 10 nmol/l amezinium had no effect and 300 nmol/l amezinium caused only 36% inhibition of deamination of noradrenaline. The results when considered with previous reports in the literature show that amezinium is about 1000 times more potent and debrisoquine is about 20 times more potent for MAO inhibition in rat lungs than in tissue homogenates, and the reason for their high potencies in the intact lungs is transport and accumulation of the drugs in the pulmonary endothelial cells by uptake1. Amezinium is much less potent as a MAO inhibitor in cells with the uptake2 transporter, such as the myocardial cells of the heart. The results also confirmed previous reports that amezinium is highly selective for MAO-A.