Deletion of IKK2 in haematopoietic cells of adult mice leads to elevated interleukin-6, neutrophilia and fatal gastrointestinal inflammation.

The IκB kinase complex, consisting of IKK1, IKK2 and the regulatory subunit NEMO, is required for NF-κB signalling following the activation of several cell surface receptors, such as members of the Tumour Necrosis Factor Receptor superfamily and the Interleukin-1 Receptor. This is critical for haematopoietic cell proliferation, differentiation, survival and immune responses. To determine the role of IKK in the regulation of haematopoiesis, we used the Rosa26Cre-ERT2 Cre/lox recombination system to achieve targeted, haematopoietic cell-restricted deletion of the genes for IKK1 or IKK2 in vivo. We found that the IKK complex plays a critical role in haematopoietic cell development and function. Deletion of IKK2, but not loss of IKK1, in haematopoietic cells led to an expansion of CD11b/Gr-1-positive myeloid cells (neutrophilia), severe anaemia and thrombocytosis, with reduced numbers of long-term haematopoietic stem cells (LT-HSCs), short-term haematopoietic stem cells (ST-HSCs) and multipotential progenitor cells (MPPs), increased circulating interleukin-6 (IL-6) and severe gastrointestinal inflammation. These findings identify distinct functions for the two IKK catalytic subunits, IKK1 and IKK2, in the haematopoietic system.

Accuracy of kinetic perimetry assessment with the Humphrey 850; an exploratory comparative study.

AIM: To compare kinetic perimetry on the Humphrey 850 and Octopus 900 perimeters for assessment of visual fields, uniocular rotations and fields of binocular single vision. METHODS: Prospective cross section study comparing Humphrey 850 kinetic perimetry to kinetic perimetry using the Octopus 900. Results were compared for both perimeters for the measurement of visual field boundaries, uniocular rotations and fields of binocular single vision in subjects with normal visual function, with comparisons of mean vector extremity values and duration of testing. A visual field boundary overlay was used to assess detection potential of Humphrey 850 kinetic perimetry using I4e and I2e targets in results of known abnormal visual fields. RESULTS: Fifteen subjects (30 eyes) with normal parameters of visual function underwent dual perimetry assessment. Mean visual field boundaries and ocular rotation extremity values were similar for Humphrey and Octopus kinetic perimetry along horizontal meridians. Measurements for Humphrey perimetry were significantly smaller for superior and inferior visual field and rotations with ceiling effects at approximately 40 and 50 degrees, respectively. Use of visual field boundary overlays for 140 patient results showed high detection of the known abnormal visual field results by the Humphrey 850 perimeter (91.4% with I4e target; 95% with I2e target) but with notable exceptions for peripheral superior visual field defects. CONCLUSIONS: The Humphrey perimeter's aspheric bowl introduces a ceiling effect for measurements in the superior and inferior visual field at approximately 40 and 50 degrees respectively. This results in potential diagnostic accuracy issues when measuring uniocular rotations, fields of binocular single and visual field boundaries in conditions that specifically impair superior and/or inferior ocular motility (e.g., thyroid eye disease) or visual fields (e.g., chiasmal compression).

Interventions for eye movement disorders due to acquired brain injury.

BACKGROUND: Acquired brain injury can cause eye movement disorders which may include: strabismus, gaze deficits and nystagmus, causing visual symptoms of double, blurred or 'juddery' vision and reading difficulties. A wide range of interventions exist that have potential to alleviate or ameliorate these symptoms. There is a need to evaluate the effectiveness of these interventions and the timing of their implementation. OBJECTIVES: We aimed to assess the effectiveness of any intervention and determine the effect of timing of intervention in the treatment of strabismus, gaze deficits and nystagmus due to acquired brain injury. We considered restitutive, substitutive, compensatory or pharmacological interventions separately and compared them to control, placebo, alternative treatment or no treatment for improving ocular alignment or motility (or both). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (containing the Cochrane Eyes and Vision Trials Register) (2017, Issue 5), MEDLINE Ovid, Embase Ovid, CINAHL EBSCO, AMED Ovid, PsycINFO Ovid, Dissertations & Theses (PQDT) database, PsycBITE (Psychological Database for Brain Impairment Treatment Efficacy), ISRCTN registry, ClinicalTrials.gov, Health Services Research Projects in Progress (HSRProj), National Eye Institute Clinical Studies Database and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The databases were last searched on 26 June 2017. No date or language restrictions were used in the electronic searches for trials. We manually searched the Australian Orthoptic Journal, British and Irish Orthoptic Journal, and ESA, ISA and IOA conference proceedings. We contacted researchers active in this field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of any intervention for ocular alignment or motility deficits (or both) due to acquired brain injury. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. We used standard methods expected by Cochrane. We employed the GRADE approach to interpret findings and assess the quality of the evidence. MAIN RESULTS: We found five RCTs (116 participants) that were eligible for inclusion. These trials included conditions of acquired nystagmus, sixth cranial nerve palsy and traumatic brain injury-induced ocular motility defects. We did not identify any relevant studies of restitutive interventions.We identified one UK-based trial of a substitutive intervention, in which botulinum toxin was compared with observation in 47 people with acute sixth nerve palsy. At four months after entry into the trial, people given botulinum toxin were more likely to make a full recovery (reduction in angle of deviation within 10 prism dioptres), compared with observation (risk ratio 1.19, 95% CI 0.96 to 1.48; low-certainty evidence). These same participants also achieved binocular single vision. In the injection group only, there were 2 cases of transient ptosis out of 22 participants (9%), and 4 participants out of 22 (18%) with transient vertical deviation; a total complication rate of 24% per injection and 27% per participant. All adverse events recovered. We judged the certainty of evidence as low, downgrading for risk of bias and imprecision. It was not possible to mask investigators or participants to allocation, and the follow-up between groups varied.We identified one USA-based cross-over trial of a compensatory intervention. Oculomotor rehabilitation was compared with sham training in 12 people with mild traumatic brain injury, at least one year after the injury. We judged the evidence from this study to be very low-certainty. The study was small, data for the sham training group were not fully reported, and it was unclear if a cross-over study design was appropriate as this is an intervention with potential to have a permanent effect.We identified three cross-over studies of pharmacological interventions for acquired nystagmus, which took place in Germany and the USA. These studies investigated two classes of pharmacological interventions: GABAergic drugs (gabapentin, baclofen) and aminopyridines (4-aminopyridines (AP), 3,4-diaminopyridine (DAP)). We judged the evidence from all three studies as very low-certainty because of small numbers of participants (which led to imprecision) and risk of bias (they were cross-over studies which did not report data in a way that permitted estimation of effect size).One study compared gabapentin (up to 900 mg/day) with baclofen (up to 30 mg/day) in 21 people with pendular and jerk nystagmus. The follow-up period was two weeks. This study provides very low-certainty evidence that gabapentin may work better than baclofen in improving ocular motility and reducing participant-reported symptoms (oscillopsia). These effects may be different in pendular and jerk nystagmus, but without formal subgroup analysis it is unclear if the difference between the two types of nystagmus was chance finding. Quality of life was not reported. Ten participants with pendular nystagmus chose to continue treatment with gabapentin, and one with baclofen. Two participants with jerk nystagmus chose to continue treatment with gabapentin, and one with baclofen. Drug intolerance was reported in one person receiving gabapentin and in four participants receiving baclofen. Increased ataxia was reported in three participants receiving gabapentin and two participants receiving baclofen.One study compared a single dose of 3,4-DAP (20 mg) with placebo in 17 people with downbeat nystagmus. Assessments were made 30 minutes after taking the drug. This study provides very low-certainty evidence that 3,4-DAP may reduce the mean peak slow-phase velocity, with less oscillopsia, in people with downbeat nystagmus. Three participants reported transient side effects of minor perioral/distal paraesthesia.One study compared a single dose of 4-AP with a single dose of 3,4-DAP (both 10 mg doses) in eight people with downbeat nystagmus. Assessments were made 45 and 90 minutes after drug administration. This study provides very low-certainty evidence that both 3,4-DAP and 4-AP may reduce the mean slow-phase velocity in people with downbeat nystagmus. This effect may be stronger with 4-AP. AUTHORS' CONCLUSIONS: The included studies provide insufficient evidence to inform decisions about treatments specifically for eye movement disorders that occur following acquired brain injury. No information was obtained on the cost of treatment or measures of participant satisfaction relating to treatment options and effectiveness. It was possible to describe the outcome of treatment in each trial and ascertain the occurrence of adverse events.

Hypoglycaemia in cystic fibrosis: An analysis of a single centre adult cystic fibrosis clinic.

BACKGROUND: Hypoglycaemia in cystic fibrosis (CF) is known to occur during oral glucose tolerance tests (OGTT) and continuous glucose monitoring, however demographic, clinical and mechanistic data are limited. The aims of this study were to review patient electronic medical records (EMR) in order to 1) describe patient characteristics of a university teaching hospital CF clinic, 2) determine the prevalence of hypoglycaemia on OGTT and explore associations with demographic and clinical characteristics, and 3) explore patient reported symptoms suggestive of hypoglycaemia documented in the EMR. METHODS: Adults who attended the RPA CF clinic between January 2009 to April 2016 were included in the study. The prevalence of hypoglycaemia on OGTT was determined and clinical and demographic data were compared to age, sex and glucose tolerance matched controls. Reported symptoms suggestive of hypoglycaemia documented in EMR were qualitatively explored. RESULTS: Hypoglycaemia on OGTT was prevalent in 25 (3 fasting and 22 reactive) of 169 patients who had an OGTT. They were heavier, less likely to have pancreatic insufficiency and had a lower insulin response at 2-h. Another 14 patients reported symptoms suggestive of hypoglycaemia in their EMR. No patient appropriately suppressed insulin at 2-h on OGTT. CONCLUSIONS: This study identified two potentially different presentations of hypoglycaemia occur in different clinic sub-populations. Knowledge gaps in the aetiology and triggers of hypoglycaemia remain.

Botulinum toxin for the treatment of strabismus.

BACKGROUND: The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison to other treatment options for strabismus. OBJECTIVES: The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2016), Embase (January 1980 to July 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We handsearched the British and Irish Orthoptic Journal, Australian Orthoptic Journal, proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA) and International Orthoptic Association (IOA) (www.liv.ac.uk/orthoptics/research/search.htm) and American Academy of Paediatric Ophthalmology and Strabismus meetings (AAPOS). We contacted researchers who are active in this field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTS) of any use of botulinum toxin treatment for strabismus. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. We used standard methods expected by Cochrane and assessed the certainty of the evidence using GRADE. We defined ocular alignment as an angle of deviation of less than or equal to 10 prism dioptres. MAIN RESULTS: Six RCTs were eligible for inclusion. We judged the included studies as at a mixture of low, unclear and high risk of bias. We did not consider any of the included studies as at low risk of bias for all domains.Two trials conducted in Spain (102 people, number of eyes not specified) compared botulinum toxin with surgery in children that required retreatment for acquired or infantile esotropia. These two studies provided low-certainty evidence that children who received botulinum toxin may have a similar or slightly reduced chance of achieving ocular alignment (pooled risk ratio (RR) 0.91, 95% confidence interval (CI) 0.71 to 1.16), binocular single vision (RR 0.88, 95% CI 0.63 to 1.23), sensory fusion (RR 0.88, 95% CI 0.63 to 1.23) and stereopsis (RR 0.86, 95% CI 0.59 to 1.25) compared with children who received surgery. One trial from Canada compared botulinum toxin with surgery in 30 adults (30 eyes) with horizontal strabismus and reported a reduced chance of ocular alignment with botulinum toxin (RR 0.38, 95% CI 0.17 to 0.85; low-certainty evidence).One trial in the UK suggested that botulinum toxin may result in a similar or slightly improved chance of ocular alignment in people with acute onset sixth nerve palsy compared with observation (RR 1.19, 95% CI 0.96 to 1.48; 47 participants, low-certainty evidence).Very low-certainty evidence from one trial from Brazil suggested that adjuvant botulinum toxin in strabismus surgery may increase the chances of ocular alignment compared with strabismus surgery alone (RR 1.83, 95% CI 0.41 to 8.11; 23 participants).One trial from China of 47 participants (94 eyes) suggested that people receiving botulinum toxin combined with sodium hyaluronate may have a similar or slightly reduced chance of achieving ocular alignment compared with botulinum toxin alone (RR 0.81, 95% CI 0.36 to 1.82; low-certainty evidence).Reported complications in people given botulinum toxin in the included trials included ptosis (range 9% to 41.66%) and vertical deviation (range 8.3% to 18.51%). Ptosis occurred less frequently when treated with botulinum toxin combined with sodium hyaluronate compared to botulinum toxin alone. AUTHORS' CONCLUSIONS: Most published literature on the use of botulinum toxin in the treatment of strabismus consists of retrospective studies, cohort studies or case reviews. Although these provide useful descriptive information, clarification is required as to the effective use of botulinum toxin as an independent treatment modality. Six RCTs on the therapeutic use of botulinum toxin in strabismus, graded as low and very low-certainty evidence, have shown varying responses. These include a lack of evidence for effect of botulinum toxin on reducing visual symptoms in acute sixth nerve palsy, poor response in people with horizontal strabismus without binocular vision, similar or slightly reduced achievement of successful ocular alignment in children with esotropia and potential increased achievement of successful ocular alignment where surgery and botulinum toxin are combined. Further high quality trials using robust methodologies are required to compare the clinical and cost effectiveness of various forms of botulinum toxin (e.g. Dysport, Xeomin, etc), to compare botulinum toxin with and without adjuvant solutions and to compare botulinum toxin to alternative surgical interventions in strabismus cases with and without potential for binocular vision.

A Randomised Controlled Trial of Treatment for Post-Stroke Homonymous Hemianopia: Screening and Recruitment.

The authors report the screening process and recruitment figures for the VISION (Visual Impairment in Stroke; Intervention Or Not) trial. This is a prospective, randomised, single-blinded, three-arm controlled trial in 14 UK acute hospital stroke units. Stroke teams identified stroke survivors suspected as having homonymous hemianopia. Interventions included Fresnel prisms versus visual search training versus standard care (information only). Primary outcome was change in visual field assessment from baseline to 26 weeks. Secondary measures included change in quality-of-life questionnaires. Recruitment opened in May 2011. A total of 1171 patients were screened by the local principal investigators. Of 1171 patients, 178 (15.2%) were eligible for recruitment: 87 patients (7.4%) provided consent and were recruited; 91 patients (7.8%) did not provide consent, and 993 of 1171 patients (84.8%) failed to meet the eligibility criteria. Almost half were excluded due to complete/partial recovery of hemianopia (43.6%; n = 511). The most common ineligibility reason was recovery of hemianopia. When designing future trials in this area, changes in eligibility criteria/outcome selection to allow more patients to be recruited should be considered, e.g., less stringent levels of visual acuity/refractive error. Alternative outcomes measurable in the home environment, rather than requiring hospital attendance for follow-up, could facilitate increased recruitment.

Detection of Visual Field Loss in Pituitary Disease: Peripheral Kinetic Versus Central Static.

Visual field assessment is an important clinical evaluation for eye disease and neurological injury. We evaluated Octopus semi-automated kinetic peripheral perimetry (SKP) and Humphrey static automated central perimetry for detection of neurological visual field loss in patients with pituitary disease. We carried out a prospective cross-sectional diagnostic accuracy study comparing Humphrey central 30-2 SITA threshold programme with a screening protocol for SKP on Octopus perimetry. Humphrey 24-2 data were extracted from 30-2 results. Results were independently graded for presence/absence of field defect plus severity of defect. Fifty patients (100 eyes) were recruited (25 males and 25 females), with mean age of 52.4 years (SD = 15.7). Order of perimeter assessment (Humphrey/Octopus first) and order of eye tested (right/left first) were randomised. The 30-2 programme detected visual field loss in 85%, the 24-2 programme in 80%, and the Octopus combined kinetic/static strategy in 100% of eyes. Peripheral visual field loss was missed by central threshold assessment. Qualitative comparison of type of visual field defect demonstrated a match between Humphrey and Octopus results in 58%, with a match for severity of defect in 50%. Tests duration was 9.34 minutes (SD = 2.02) for Humphrey 30-2 versus 10.79 minutes (SD = 4.06) for Octopus perimetry. Octopus semi-automated kinetic perimetry was found to be superior to central static testing for detection of pituitary disease-related visual field loss. Where reliant on Humphrey central static perimetry, the 30-2 programme is recommended over the 24-2 programme. Where kinetic perimetry is available, this is preferable to central static programmes for increased detection of peripheral visual field loss.

Botulinum toxin for the treatment of strabismus.

BACKGROUND: The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However it is unclear how effective its use is in comparison to other treatment options for strabismus. OBJECTIVES: To evaluate the efficacy of botulinum toxin in the treatment of strabismus compared with alternative treatment options, to investigate dose effect and complication rates. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 11), MEDLINE (January 1950 to December 2011), EMBASE (January 1980 to December 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 5 December 2011. We manually searched the Australian Orthoptic Journal and British and Irish Orthoptic Journal and ESA, ISA and IOA conference proceedings. We attempted to contact researchers who are active in this field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTS) of any use of botulinum toxin treatment for strabismus. DATA COLLECTION AND ANALYSIS: Each review author independently assessed study abstracts identified from the electronic and manual searches. Author analysis was then compared and full papers for appropriate studies were obtained. MAIN RESULTS: We found four RCTs that were eligible for inclusion. Two trials found that there was no difference between the use of botulinum toxin and surgery for patients requiring retreatment for acquired esotropia or infantile esotropia. There was no evidence for a prophylactic effect of botulinum toxin in a treatment trial of acute onset sixth nerve palsy. Botulinum toxin had a poorer response than surgery in a trial of patients requiring treatment for horizontal strabismus in the absence of binocular vision. Reported complications included ptosis and vertical deviation and ranged from 24% in a trial using Dysport™ to 52.17% and 55.54% in trials using Botox™. AUTHORS' CONCLUSIONS: The majority of published literature on the use of botulinum toxin in the treatment of strabismus consists of retrospective studies, cohort studies or case reviews. Although these provide useful descriptive information, clarification is required as to the effective use of botulinum toxin as an independent treatment modality. Four RCTs on the therapeutic use of botulinum toxin in strabismus have shown varying responses ranging from a lack of evidence for prophylactic effect of botulinum toxin in acute sixth nerve palsy, to poor response in patients with horizontal strabismus without binocular vision, to no difference in response in patients that required retreatment for acquired esotropia or infantile esotropia. It was not possible to establish dose effect information. Complication rates for use of Botox™ or Dysport™ ranged from 24% to 55.54%.

p53-Dependent transcriptional responses to interleukin-3 signaling.

p53 is critical in the normal response to a variety of cellular stresses including DNA damage and loss of p53 function is a common feature of many cancers. In hematological malignancies, p53 deletion is less common than in solid malignancies but is associated with poor prognosis and resistance to chemotherapy. Compared to their wild-type (WT) counterparts, hematopoietic progenitor cells lacking p53 have a greater propensity to survive cytokine loss, in part, due to the failure to transcribe Puma, a proapoptotic Bcl-2 family member. Using expression arrays, we have further characterized the differences that distinguish p53(-/-) cells from WT myeloid cells in the presence of Interleukin-3 (IL-3) to determine if such differences contribute to the increased clonogenicity and survival responses observed in p53(-/-) cells. We show that p53(-/-) cells have a deregulated intracellular signaling environment and display a more rapid and sustained response to IL-3. This was accompanied by an increase in active ERK1/2 and a dependence on an intact MAP kinase signaling pathway. Contrastingly, we find that p53(-/-) cells are independent on AKT for their survival. Thus, loss of p53 in myeloid cells results in an altered transcriptional and kinase signaling environment that favors enhanced cytokine signaling.

Investigation of the role of computed tomography as an adjunct to autopsy in the evaluation of stillbirth.

INTRODUCTION: The number of parents agreeing to autopsy following stillbirth is declining, which has undermined clinicians' ability to assess causes of intrauterine death and can impact counselling regarding recurrence. Post-mortem radiological imaging is a potential alternative method of investigating perinatal loss. The aim of this study was to assess the role of multi-detector computed tomography (MDCT) in the investigation of stillbirth. STUDY DESIGN: Following ethical approval and written consent, parents were offered MDCT of the stillborn infant. MDCT was performed with 3D reconstruction, and images were analysed for image quality, anthropomorphic measurements and pathologic findings. Body part and organ-specific measurements were performed; including head, chest and abdominal circumferences, and muscle and liver mass was also measured. Findings were correlated with obstetric history, post-mortem skeletal survey (plain radiography), and formal autopsy. RESULTS: Fourteen third-trimester stillborn infants were scanned. Image quality was moderate to excellent for most body structures. CT was better than plain radiography for imaging skeletal structures and large solid organs and demonstrated a range of pathologies including renal vein thrombosis, mesenteric calcification and skeletal hyperostosis that were not seen on plain radiographs. MDCT did not overlook autopsy findings and provided some additional information. CONCLUSION: This study confirms the feasibility of MDCT in the investigation of third trimester stillbirth. MDCT image quality is acceptable and the examination can demonstrate a range of anatomic and pathologic findings. Initially, its value may be as an important adjunct to conventional autopsy.

Atlantoaxial rotatory fixation after ventriculoperitoneal shunting.

Ventriculoperitoneal (VP) shunting is a common neurosurgical procedure in the pediatric population. Atlantoaxial rotatory fixation (AARF) is not uncommon in this same group. We present the first reported case of AARF following a VP shunt procedure. A 10-year-old boy, with hydrocephalus and a left temporal arachnoid cyst since birth, underwent a revision of his VP and cystoperitoneal shunts. A second operation was performed 2 days later to optimize catheter placement. Postoperative neck pain was attributed to tunneling of the subcutaneous catheter. 2 months after surgery, the child had minimal neck discomfort but maintained his head in a "cock-robin" position. Plain radiographs and computed tomographic (CT) images confirmed AARF. The child was admitted and placed in halo traction. After 3 days of traction, analgesics, sedation, and muscle relaxants, anatomic re-alignment of the C1-C2 vertebral complex was confirmed on CT scan. Following 3 months of immobilization in a halo-vest apparatus, the halo was removed. At 8-year follow-up, the clinical examination is normal and repeat imaging studies remain normal. Due to surgical positioning, and postoperative signs attributed to normal postoperative pain, an AARF was not initially recognized. This case represents the first time that AARF has been reported following a VP shunt procedure.

The psychosocial effects of adult strabismus: a review.

Correction of adult strabismus is not a cosmetic procedure but one that restores normality to an individual's appearance that has been altered by a disease process. Two fundamental principles underpinning facial attractiveness are symmetry and averageness-manifest strabismus affects both of these giving an unconscious signal of poor genetic history. The presence of manifest strabismus adversely affects many aspects of patients' lives including finding a partner, job prospects and interaction with peers, and may manifest more seriously as psychiatric disorders. Surgical correction has been shown to be safe and effective for the functional problems of strabismus in adults but the hugely positive effects on the psychosocial aspects are only now becoming apparent. The advent of a new adult strabismus specific quality-of-life questionnaire and its subsequent validation will make this quantification of improvement easier. The wider medical community and the public at large should be made aware of the benefits of corrective strabismus surgery in adults.

The psychosocial effects of strabismus: effect of patient demographics on the AS-20 score.

PURPOSE: The introduction of the AS-20 strabismus-specific quality-of-life questionnaire allows clinicians to quantify the effects of strabismus on adults for the first time. We correlated strabismic patients' demographic and clinical findings to their AS-20 scores. METHODS: A consecutive cohort of patients from an ongoing prospective study of adults with manifest strabismus was recruited. The patients' age, sex, socioeconomic status (SES), magnitude, and direction of deviation were correlated to their AS-20 scores. Patients' zip codes were used to derive a score for their SES based on the English 2007 Index of Multiple Deprivation score (IMD2007). RESULTS: A total of 61 questionnaires with all demographic and clinical data were available. The median magnitude of deviation was 20.4(Δ) in this group. The mean AS-20 score was 49.5 (SD 21.6). Women had significantly lower AS-20 scores than men (p = 0.02). There was no difference in AS-20 scores between individuals with eso- and exodeviations (p = 0.7). Multiple linear regression analysis shows female sex and lower SES to be significantly associated with lower AS-20 scores (p = 0.03 and p = 0.006, respectively). CONCLUSIONS: Strabismic patients who are female or live in a more deprived area have a significantly lower AS-20 score.

Dose effect of botulinum toxin a in heterotropia and heterophoria.

PURPOSE: To evaluate the short-term dose effect of botulinum toxin in manifest and intermittent horizontal strabismus types. METHODS: Dysport of 2 international units was injected into a single muscle in cases of constant esotropia and exotropia plus decompensating esophoria and exophoria. Electromyography (EMG) signal was recorded during each procedure. Angle of deviation was measured in each case pretreatment and posttreatment at 2 weeks by prism cover test for near and distance fixation. Change in deviation was evaluated by nonparametric statistical evaluation. RESULTS: Sixty-six patients were reviewed: 30 males and 36 females. The mean age was 24 years (1-79: SD 20.4). Of the 66 patients, 28 had botulinum toxin to the right eye and 38 had it to the left eye. Thirty-nine had eso deviations (19 constant, 20 intermittent) and 27 had exo deviations (12 constant, 15 intermittent). EMG signal was classed as excellent (30%), good (26%), low (6%), or absent (38%). Percentage net change in angle of deviation was 52% to 60% for eso and exo deviations at near and distance fixation. No association was found in extent of reduction of angle of deviation for type of deviation, presence of constant or intermittent deviation, eye injected, or EMG signal. CONCLUSIONS: All changes in angle of deviation were significant. Larger pretreatment angles of deviation did not preclude significant changes in angle of deviation using botulinum toxin and significantly greater change in deviation was seen in pretreatment angles greater than 20PD.

Ketamine and botulinum: a safe combinationfor the management of childhood strabismus.

AIMS: To determine the prevalence of ketamine side effects in children receiving botulinum toxin injections for strabismus under ketamine anesthesia and to establish the prevalence, severity, and duration of ptosis in these children. METHODS: Children who had undergone ketamine anesthesia for botulinum toxin injections (1999 to 2006) to correct strabismus were identified in a retrospective review. A questionnaire to establish occurrence of nightmares, sleepless nights, hallucinations (ketamine side effects), or ptosis (botulinum toxin side effect), was sent to parents or guardians. Details of side effects were obtained by telephone and the patients' medical records were analyzed. RESULTS: Questionnaires were sent to 113 patients (total of 130 injections). Ninety-seven (114 injections) completed questionnaires were returned. Emergence reactions were experienced by 12 patients (12.4%). Two children experienced sleepless nights, nightmares, and hallucinations. The remaining 10 experienced one side effect only. Eighteen children had ptosis at their 2-week follow-up appointment, most which resolved within 6 weeks. There were no life-threatening or sight-threatening adverse events. CONCLUSIONS: Botulinum toxin injection under intravenous ketamine anesthesia can safely be used for children. Ketamine anesthesia may be associated with side effects, namely hallucinations and sleep disturbances.

Myeloid progenitor cells lacking p53 exhibit delayed up-regulation of Puma and prolonged survival after cytokine deprivation.

Loss of p53-dependent apoptosis contributes to the development of hematologic malignancies and failure to respond to treatment. Proapoptotic Bcl-2 family member Puma is essential for apoptosis in HoxB8-immortalized interleukin-3 (IL-3)-dependent myeloid cell lines (FDM cells) provoked by IL-3 deprivation. p53 and FoxO3a can transcriptionally regulate Puma. To investigate which transcriptional regulator is responsible for IL-3 deprivation-induced Puma expression and apoptosis, we generated wild-type (WT), p53(-/-), and FoxO3a(-/-) FDM cells and found that p53(-/-) but not FoxO3a(-/-) cells were protected against IL-3 withdrawal. Loss of p21(cip/waf), which is critical for p53-mediated cell-cycle arrest, afforded no protection against IL-3 deprivation. A survival advantage was also observed in untransformed p53(-/-) hematopoietic progenitor cells cultured in the presence or absence of cytokines. In response to IL-3 deprivation, increased Puma protein levels in p53(-/-) cells were substantially delayed compared with WT cells. Increased p53 transcriptional activity was detected after cytokine deprivation. This was substantially less than that induced by DNA damage and associated not with increased p53 protein levels but with loss of the p53 regulator, MDM2. Thus, we conclude that p53 protein is activated after IL-3 deprivation by loss of MDM2. Activated p53 transcriptionally up-regulates Puma, which initiates apoptosis.

Botulinum toxin for the treatment of strabismus.

BACKGROUND: The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However it is unclear how effective its use is in comparison to other treatment options for strabismus. OBJECTIVES: To evaluate the efficacy of botulinum toxin in the treatment of strabismus compared with alternative treatment options, to investigate dose effect and complication rates. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE and LILACS up to 15 December 2008. We manually searched the Australian Orthoptic Journal and British and Irish Orthoptic Journal and ESA, ISA and IOA conference proceedings. We attempted to contact researchers who are active in this field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTS) of any use of botulinum toxin treatment for strabismus. DATA COLLECTION AND ANALYSIS: Each review author independently assessed study abstracts identified from the electronic and manual searches. Author analysis was then compared and full papers for appropriate studies were obtained. MAIN RESULTS: We found four RCTs that were eligible for inclusion. Two trials found that there was no difference between the use of botulinum toxin and surgery for patients requiring retreatment for acquired esotropia or infantile esotropia. There was no evidence for a prophylactic effect of botulinum toxin in a treatment trial of acute onset sixth nerve palsy. Botulinum toxin had a poorer response than surgery in a trial of patients requiring treatment for horizontal strabismus in the absence of binocular vision. Reported complications included ptosis and vertical deviation and ranged from 24% in a trial using Dysport to 52.17% and 55.54% in trials using Botox. AUTHORS' CONCLUSIONS: The majority of published literature on the use of botulinum toxin in the treatment of strabismus consists of retrospective studies, cohort studies or case reviews. Although these provide useful descriptive information, clarification is required as to the effective use of botulinum toxin as an independent treatment modality. Four RCTs on the therapeutic use of botulinum toxin in strabismus have shown varying responses ranging from a lack of evidence for prophylactic effect of botulinum toxin in acute sixth nerve palsy, to poor response in patients with horizontal strabismus without binocular vision, to no difference in response in patients that required retreatment for acquired esotropia or infantile esotropia. It was not possible to establish dose effect information. Complication rates for use of Botox or Dysport ranged from 24% to 55.54%.

Standardising practices through form design and education improves insulin management.

Diabetes is common in hospitalised patients and insulin is frequently required for management. Insulin is a high-risk drug, accounting for about 15% of reported medication-related incidents. Despite its complexity, insulin management in hospitals is often undertaken by junior and non-specialist staff. Improving insulin management requires addressing safe prescribing and administration as well as quality use of insulin. Common errors in insulin use are well documented and can be addressed through form design and enhancing decision support. We undertook to improve insulin management using a locally proven improvement methodology. New forms were developed for intravenous and subcutaneous insulin and blood glucose management. Audited pilot studies in four hospitals confirmed improved insulin management without adversely impacting on overall diabetes management as assessed using Glucometrics. Subsequently, the forms have been introduced to 70% of Queensland public hospitals with roll-out to remaining hospitals continuing. Large-scale standardisation of insulin management is feasible.

Bilateral combined resection and recession of the medial rectus muscle for convergence excess esotropia.

Five patients with true convergence excess esotropia were surgically managed with combined resection and recession of the medial rectus muscles. This technique was chosen to address the near/distance angle disparity. The use of this surgical technique produced full asymptomatic binocular control at near and distance fixation in four patients. One patient developed a consecutive exotropia but regained full binocular control following a second surgical procedure.

Surgical treatment for progressive esotropia in the setting of high-axial myopia.

Acquired esotropia in association with high myopia may be secondary to displacement of the lateral rectus muscle pulley system or to the mechanical restriction due to the contact between the posterior elongated globe and the orbital apex limiting rotation. We present the clinical findings and surgical management of a patient with this condition.