Museum material of Rhipicephalus sanguineus sensu Roberts (1965) collected in 1902-1964 from Australia is identical to R. sanguineus sensu lato tropical lineage at the mitochondrial DNA 12S rRNA level.

Ticks identified as Rhipicephalus sanguineus (Latreille, 1806) have been recorded in Australia since 1896. It is now recognized that ticks identified as R. sanguineus belong to different lineages. Recently, the so-called temperate lineage has been redescribed as R. sanguineus sensu stricto with a designated neotype. In Australia, the evidence suggests that only R. sanguineus sensu lato tropical lineage exists. We present a genetic evaluation of R. sanguineus sensu Roberts (1965) from museum material that was evaluated or identified by Roberts. We evaluated 12 museum specimens collected between 1913 and 1964, from various locations around Australia at the molecular level. DNA isolation was successful for 4/12 specimens. All four museum specimens were 100% identical to each other and to the reference R. sanguineus s.l. tropical lineage. Measurements of morphologically significant structures for male and female museum and contemporary tick specimens were obtained. The morphologically significant structures revealed there was no significant difference (ANOVA, P > 0.05) between these groups of male and female ticks. This study updates and supplement the comprehensive descriptions provided by Roberts (1965), which genetically belong to R. sanguineus s.l. tropical lineage.

Clinical outcomes and patient satisfaction following total hip and knee arthroplasty in patients with inherited bleeding disorders: A 20-year single-surgeon cohort.

INTRODUCTION: Persons with haemophilia and other inherited bleeding disorders are prone to disabling joint arthropathy frequently requiring arthroplasty for end-stage joint disease. Higher complication rates and more modest post-operative functional outcomes have previously been described. AIM: To evaluate the clinical outcomes and patient satisfaction of persons with inherited bleeding disorders (predominantly haemophilia) undergoing total hip and knee replacement. METHODS: Retrospective, single-centre cohort study with longitudinal assessment of patients with inherited bleeding disorders who underwent total hip and knee replacement over a 20-year period. Eligible patients were clinically assessed with Harris Hip Score (HHS), Knee Society Score (KSS), pain visual analogue scale (VAS) and a patient satisfaction questionnaire. RESULTS: Thirty-one patients (48 joints) met the inclusion criteria. Mean age at surgery was 49.3 years (SD: 13.1, range 21-75 years) with a mean follow-up of 9.33 years (1.7-19.3). The majority (26/31) of patients had haemophilia A, predominantly severe haemophilia A (22/26). Reported pain levels were low, and patient satisfaction was high. Joint-specific outcome scores were "good" to "excellent" in 67% of total hip replacement patients and 92% of total knee replacement patients. A low complication rate was observed, with 2 patients requiring revision surgery and 4 patients requiring re-operation without implant revision. CONCLUSION: Arthroplasty is a reliable procedure in patients with inherited bleeding disorders with end-stage hip or knee arthropathy. The overall complexity of this group is highlighted, and the need for multidisciplinary care is emphasised.

A record of the parasitic mite Hemimyialges macdonaldi (Evans et al. 1963) (Acari: Epidermoptidae) in the Orange-bellied Parrot Neophema chrysogaster (Latham, 1790) (Psittaciformes: Psittaculidae) in Australia.

The subcutaneous parasitic mite Hemimyialges macdonaldi was found in a specimen of the Orange-bellied Parrot Neophema chrysogaster that died in captivity. A review of the host range and geographic distribution of this mite shows it is cosmopolitan and occurs in a very wide range of birds. It does not appear to be a cause of significant mortality in its hosts.

Distinctive Brain Malformations in Zhu-Tokita-Takenouchi-Kim Syndrome.

BACKGROUND AND PURPOSE: Zhu-Tokita-Takenouchi-Kim syndrome is a severe multisystem malformation disorder characterized by developmental delay and a diverse array of congenital abnormalities. However, these currently identified phenotypic components provide limited guidance in diagnostic situations, due to both the nonspecificity and variability of these features. Here we report a case series of 7 individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome, 5 ascertained by their presentation with the neuronal migration disorder, periventricular nodular heterotopia. MATERIALS AND METHODS: Individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome were recruited from 2 sources, a high-throughput sequencing study of individuals with periventricular nodular heterotopia or from clinical diagnostic sequencing studies. We analyzed available brain MR images of recruited individuals to characterize periventricular nodular heterotopia distribution and to identify the presence of any additional brain abnormalities. RESULTS: Pathogenic variants in SON, causative of Zhu-Tokita-Takenouchi-Kim syndrome, were identified in 7 individuals. Brain MR images from these individuals were re-analyzed. A characteristic set of imaging anomalies in addition to periventricular nodular heterotopia was identified, including the elongation of the pituitary stalk, cerebellar enlargement with an abnormally shaped posterior fossa, rounding of the caudate nuclei, hippocampal malformations, and cortical anomalies including polymicrogyria or dysgyria. CONCLUSIONS: The recurrent neuroradiologic changes identified here represent an opportunity to guide diagnostic formulation of Zhu-Tokita-Takenouchi-Kim syndrome on the basis of brain MR imaging evaluation.

Oxygen tension regulates the expression of angiogenesis factor by macrophages.

When cultured in a hypoxic environment similar to that found in the center of a wound, macrophages secreted active angiogenesis factor into the medium. Under conditions similar to those of well-oxygenated tissue, macrophages did not secrete active angiogenesis factor. Macrophages that secreted the factor at hypoxic conditions stopped secreting it when returned to room air. Thus the control of angiogenesis in wound healing may be the result of macrophages responding to tissue oxygen tension without the necessity of interacting with other cell types or biochemical signals.

Mechanical responses and integrin associated protein expression by human ankle chondrocytes.

Metabolic, biochemical and biomechanical differences between ankle and knee joint cartilage and chondrocytes including resistance to the effects of catabolic cytokines and fibronectin fragments may be relevant to differences in prevalence of OA in these joints. Although there is increasing information available on how chondrocytes from knee and hip joint cartilage recognise and respond to mechanical stimuli, knowledge of mechanotransduction in ankle joint chondrocytes is limited. This study was undertaken to (i) establish whether the response of normal ankle joint derived chondrocytes to mechanical stimulation in vitro was similar to that of normal and osteoarthritic knee joint derived chondrocytes and (ii) to investigate whether these chondrocytes showed differences in expression of integrin associated regulatory and signalling molecules. Unlike normal knee joint chondrocytes, ankle joint chondrocytes did not show an increase in relative levels of aggrecan mRNA when mechanically stimulated. No obvious change in protein tyrosine phosphorylation was seen in ankle chondrocytes subsequent to mechanical stimulation but these cells expressed elevated levels of tyrosine phosphorylated proteins at rest when compared to normal knee joint chondrocytes. Ankle joint chondrocytes showed an increase in protein kinase B phosphorylation following 1 min 0.33 Hz stimulation which was inhibited by the presence of antibodies to alpha5beta1 integrin. Ankle joint chondrocytes appeared to show significant differences in levels of the integrin-associated proteins CD98, CD147 and galectin 3, PKCgamma and differences in responses to glutamate were seen. Chondrocytes from ankle and knee joint cartilage respond differently to 0.33 Hz mechanical stimulation. This may be related to modified integrin-dependent mechanotransduction as a result of changes in expression of integrin regulatory molecules such as CD98 or differential expression and function of downstream components of the mechanotransduction pathway such as PKC or NMDA receptors.

3-Sulfonyl-1-carba-1-dethiacephems.

The stability of the 1-carba-1-dethiacephalosporin framework has allowed the synthesis of a range of 3-sulfonyl-1-carba-1-dethiacephems unavailable for a variety of reasons in the cephem arena. The known p-nitrobenzyl 7 beta-(phenoxyacetamido)-3-[[(trifluoromethyl)sulfonyl]oxy]-1-carba -1- dethia-3-cephem-4-carboxylate served as a precursor to this series of compounds. Displacement of the enol triflate with various sulfinates in acetonitrile or DMF and deprotection of the intermediates led to 7 beta-[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]- 3-[alkyl(aryl)sulfonyl]-1-carba-1-dethia-3-cephem-4-carboxyl ic acids. The 3-sulfonyl-1-carba-1-dethiacephems display potent activity against both Gram-positive and Gram-negative bacteria. The following MIC's (microgram/mL) for the 3-cyclopropyl sulfone are representative: Staphylococcus aureus = 4, Streptococcus pyogenes = 1, Haemophilus influenzae = 0.25, Escherichia coli = 0.03, Enterobacter cloacae = 0.25, Proteus rettgeri = 0.25. The excellent in vitro antibacterial activity of this series indicates the potential of the carbacephalosporin framework for exploring substituents which are unknown or which produce unstable cephems.

Diagnostic accuracy of an international static-imaging telepathology consultation service.

Static-image and dynamic- (real-time) image telepathology are competing technologies. Although some studies suggest that the diagnostic accuracy of the dynamic-image telepathology approaches the accuracy of light microscopy, few reports have documented the diagnostic accuracy of static-image telepathology as used in the setting of an actual surgical pathology consultation practice. We report the results of an analysis of 171 telepathology consultation cases submitted to the Arizona-International Telemedicine Network (AITN). Digital images were submitted by pathologists from six participating institutions in Arizona, Mexico, and China. Telepathologists could render a telepathology diagnosis (TP) or defer rendering a diagnosis to obtain additional video images, glass slides for detailed analysis, or to obtain tissue blocks for special studies such as immunohistochemistry. The telepathologists rendered diagnoses for 144 cases and deferred 27 cases. Two pathologists retrospectively evaluated-glass slides from each case and rendered a consensus glass slide (GS) "truth" diagnosis. There was 88.2% concordance between TP and GS diagnoses (127 of 144 diagnoses). Concordance of 96.5% was achieved for clinically important diagnoses (139 of 144 diagnoses). Telepathologists deferred making a diagnosis to obtain glass slides for conventional light microscopy in 14 cases (8.1%) and for results of immunohistochemistry studies in 13 cases (7.6%). Thus, correct diagnoses were rendered by static-image telepathology in 127 of 171 cases (74.3%) at the time of telepathology diagnostic sessions. Inappropriate field selection and sampling biases of referring pathologists, as well as a tendency of static-image telepathologists to underestimate the complexity of some cases, may reduce the value of consultations based on the viewing of static images.

Oxygen as an antibiotic. A comparison of the effects of inspired oxygen concentration and antibiotic administration on in vivo bacterial clearance.

Since prophylactic antibiotics and changes in tissue partial pressure of oxygen may affect bacterial clearance by different mechanisms, we tested the effects of hypoxia, hyperoxia, and normoxia with and without antibiotic administration on bacterial clearance. We found that improving tissue oxygenation by administration of normobaric oxygen decreased infectious necrosis as effectively as prophylactic antibiotic administration and that improved tissue oxygenation and antibiotic administration had an additive effect. We believe that a fraction of inspired oxygen of 45% should be added to prophylactic antibiotics as standard perioperative and postoperative care.

Oxygen as an antibiotic. The effect of inspired oxygen on infection.

Granulocytes' in vitro bactericidal capacity for certain bacteria depends on an adequate environmental oxygen supply. Oxygen available to granulocytes in infected tissue is decreased by local conditions and can be altered significantly by small changes in its inspired concentration. We modified Burke's and Miles' bacteria-injection model in animals to test the effect of breathing 12%, 21%, and 45% oxygen on the size of lesions produced by intradermal injections of Escherichia coli. Moderately increased inspired oxygen concentrations (fraction of inspired oxygen [Flo2]) significantly decreased the size and number of necrotic lesions, whereas hypoxia increased both. Increasing Flo2 to 45% after three and 24 hours of hypoxia also significantly decreased lesion size. Suppression of infection by moderate hyperoxia is comparable with that reported by Burke after timely, adequate doses of type-specific antibiotics.

Effects of steroids and retinoids on wound healing.

HYPOTHESIS: Anti-inflammatory corticosteroids significantly impair wound healing. Retinoids partially, but significantly, reverse this effect. Little is known about the mechanism of steroid retardation or retinoid reversal. We hypothesized that corticosteroids lower transforming growth factor-beta (TGF-beta) and insulin-like growth factor-I (IGF-I) levels and tissue deposition in wounds and that retinoids stimulate corticosteroid-impaired TGF-beta and IGF-I release and collagen production. DESIGN: Randomized controlled trial. SETTING: Wound healing research laboratory. PARTICIPANTS: Animal study. INTERVENTIONS: Four wire mesh wound cylinders were implanted subcutaneously into the backs of 72 male Sprague-Dawley rats. Wound healing was impaired by a single subcutaneous injection of 6 mg of methylprednisolone acetate (Depo-Medrol). Two preparations of retinoids were used in separate experiments: all-trans-retinoic acid and 9-cis-retinoic acid that were fed orally. MAIN OUTCOME MEASURES: Hydroxyproline content was measured in the healing tissue and TGF-beta and IGF-I levels were analyzed in the wound fluid. RESULTS: Methylprednisolone treatment significantly decreased TGF-beta and IGF-I levels in the wound fluid and hydroxyproline content in the tissue (P<.05). Oral all-trans- and 9-cis-retinoic acid partially reversed the TGF-beta and IGF-I decrease and significantly increased hydroxyproline content toward normal levels (P<.05). Oral all-trans-retinoic acid enhanced collagen deposition, TGF-beta and IGF-I levels over normal chow fed control animals (P<.05). CONCLUSIONS: Steroids and retinoids have antagonistic effects on growth factors and collagen deposition in wound healing. These effects can be relevant for treatment options in a clinical setting.

Peptides from live yeast cell derivative stimulate wound healing.

Live yeast cell derivative is an alcoholic extract from yeast (Saccharomyces cerevisiae) that has previously been shown by three groups of workers to stimulate wound healing. Live yeast cell derivative is a complex mixture, and it was not known which of its many components was responsible for the biological activity. This study describes the separation and analysis of the major components, one of which is a peptide fraction that stimulates wound healing. The fraction consists of a mixture of peptides from 6000 to 17,000 d. It causes angiogenesis in a chick embryo yolk sac membrane assay and in a rabbit cornea assay, and it dramatically stimulates wound healing in the "Schilling/Hunt" wire mesh cylinder model at concentrations 25-fold lower than those required for the intact live yeast cell derivative.

Precarved lyophilized tissue for lamellar keratoplasty in recurrent pterygium.

Thirteen eyes with recurrent pterygia were treated with excision and lamellar keratoplasty using precarved, lyophilized donor cornea. After an average follow-up of 23 months, only one eye (7.7%) required repeat excision. Two eyes (15.4%) had minor recurrences that were asymptomatic and did not progress. Minimal vascularization at the interface between donor and recipient cornea was frequent, but this completely regressed after suture removal and topical corticosteroid treatment. Limitation of movement, when present preoperatively, was improved or eliminated. Best corrected visual acuity was unchanged in eight eyes (61.5%), decreased by one line in two eyes (15.4%), and improved by one or two lines in three eyes (23.1%). Postoperative astigmatism was within 0.5 diopter of the preoperative value in 11 eyes (84.6%); one eye (7.7%) had a postoperative increase of 1 diopter and another eye (7.7%) of 2 diopters.

A new surgical head rest.

A surgical head rest is described that gives good wrist support, provides space to place instruments, and allows drainage of irrigation fluid.

Refractive and visual results and patient satisfaction after excimer laser photorefractive keratectomy for myopia.

A study of excimer laser photorefractive keratectomy was performed on 108 patients. Variation in individual refractive outcome was noted, particularly for the higher levels of correction. At 12 months, of those with up to 3 dioptres of myopia, 93% were within 1 dioptre of emmetropia, 100% achieved an acuity of 6/12 unaided, 69% were very pleased with their result, and 10% were very disappointed. Of those with between 3.1 and 6 dioptres of myopia, the respective figures were 75%, 73%, 65%, and 11%. For those with over 6 dioptres of myopia the respective figures were 46%, 58%, 38%, and 23%. Some patients were disappointed despite having achieved good unaided visual acuity. Forty seven per cent of patients lost at least one Snellen line of best corrected acuity. Glare was a problem for some of the time in over 60%. Perceived distortion of vision was a problem for all of the time in 11% to 31% of cases depending on the initial level of myopia. In some cases the refraction continued to change between 12 months and 20 months.

A forced-choice test improves clinical contrast sensitivity testing.

Decreased contrast sensitivity has been demonstrated in early glaucoma, but the deficit in not regularly observed. We designed a prototype for a forced-choice printed test and evaluated it with several other measures of contrast sensitivity. The results also bear on the pattern of loss and the variables which effect performance. Mildly glaucomatous patients show at 6 db (50%) loss of contrast sensitivity at all spatial frequencies tested compared with age matched controls. Moving gratings give the same information as stationary ones, and practice effects are negligible. Contrast sensitivity at or below 2 cycles/degree is poorly correlated with visual acuity and does not change with age in the forced-choice test. Subjective judgment made the apparent contrast threshold higher, age dependent, and more variable, particularly at higher spatial frequencies. The pattern of variability can explain some reports of insignificant effects and why low spatial frequency contrast sensitivity detects glaucoma better than visual acuity. Methods correlated so poorly, despite high reliabilities, that uncontrolled biases must be suspected in subjective measures. Our new forced-choice format was superior to all other tests on at least one formal criterion and always at least equal to them. Improvements in contrast sensitivity screening tests are thus indicated.

Epikeratophakia for aphakia, keratoconus, and myopia.

A series of 67 cases of epikeratophakia is presented with an average time from surgery of 12.2 months. For aphakia there was a delay in the recovery of vision, but by nine months 83% of 57 patients achieved an acuity equal to, or within 1 line of, the preoperative value. 57% were corrected to within 3 dioptres of emmetropia, but in the latter part of the series 75% were within this range. Astigmatism and reduced contrast sensitivity, especially in the presence of glare, were important complications. For keratoconus, 86% of seven patients with over two months of follow-up achieved a spectacle corrected acuity of 6/9 or better. One patient had surgery for myopia and obtained the desired refractive correction.

Comparison of 2 interferometers for predicting visual acuity in patients with cataract.

Two clinical interferometers generated gratings directly on to the retina in young experienced observers and also in patients about to undergo cataract surgery. Eyes in the patients with no media opacities were used as controls. We agreed with the manufacturers' claims that gratings are seen on the retina independent of refractive state and that gratings can still be seen through most cataracts. However, we did not find that preoperative retinal visual acuity was of any value in predicting postoperative Snellen visual acuity. Reasons for this are discussed.

Effect of donor parameters on primary graft failure and the recovery of acuity after keratoplasty.

A retrospective evaluation was made of 983 penetrating corneal grafts. Donor corneas stored in either K-Sol or McCarey-Kaufman media had a significantly greater rate of primary graft failure (about 2%) than those kept in moist chamber storage (0%). Selected subgroups of 50 corneas from each storage system were studied to determine the time taken to reach a postoperative acuity of 6/12. No significant correlation was found between this time and either the duration of storage of donor corneas or the age of donor. A significant delay in recovery of visual acuity was found with increasing age of recipient. The increased average time from donor death to surgery for K-Sol (56 hours) and McCarey-Kaufman (40 hours) corneas compared with moist chamber corneas (15 hours) facilitated the scheduling of surgery at the cost of increased chance of primary graft failure.

Surgical management of essential blepharospasm.

We have reviewed the surgical management of essential blepharospasm over the last 15 years, comparing the results from facial nerve avulsion with those from orbicularis muscle stripping. After facial nerve avulsion 50% of patients remained free of troublesome spasm for 15 months after surgery, but only 25% remained so for more than two years. Following orbicularis oculi myectomy 50% of patients were free of troublesome spasms for 30 months after surgery and 55% of patients had relief from spasm for more than two years. Secondary effects of the two procedures are compared and are found to be fewer after orbicularis myectomy. There were no major complications after either form of surgery. Botulinum toxin is the treatment of first choice for this condition. If this becomes ineffective or inconvenient, surgical treatment is warranted and should not be deferred for fear of severe side effects of treatment, since these are rare. Protractor myectomy gives longer relief from blepharospasm than facial nerve avulsion and has fewer complications. However, it is technically difficult, time consuming, and has greater peroperative morbidity. Facial nerve avulsion may therefore still have a role in selected patients.