A population pharmacokinetic model to guide clozapine dose selection, based on age, sex, ethnicity, body weight and smoking status.

AIMS: Guidance on clozapine dosing in treatment-resistant schizophrenia is based largely on data from White young adult males. This study aimed to investigate the pharmacokinetic profiles of clozapine and N-desmethylclozapine (norclozapine) across the age range, accounting for sex, ethnicity, smoking status and body weight. METHODS: A population pharmacokinetic model, implemented in Monolix, that linked plasma clozapine and norclozapine via a metabolic rate constant, was used to analyse data from a clozapine therapeutic drug monitoring service, 1993-2017. RESULTS: There were 17 787 measurements from 5960 patients (4315 male) aged 18-86 years. The estimated clozapine plasma clearance was reduced from 20.2 to 12.0 L h-1 between 20 and 80 years. Model-based dose predictions to attain a predose plasma clozapine concentration of 0.35 mg L-1 was 275 (90% prediction interval 125, 625) mg day-1 in nonsmoking, White males weighing 70 kg and aged 40 years. The corresponding predicted dose was increased by 30% in smokers, decreased by 18% in females, and was 10% higher and 14% lower in otherwise analogous Afro-Caribbean and Asian patients, respectively. Overall, the predicted dose decreased by 56% between 20 and 80 years. CONCLUSION: The large sample size and wide age range of the patients studied allowed precise estimation of dose requirements to attain predose clozapine concentration of 0.35 mg L-1 . The analysis was, however, limited by the absence of data on clinical outcome and future studies are required to determine optimal predose concentrations specifically in those aged over 65 years.

PERFECTED enhanced recovery pathway (PERFECT-ER) versus standard acute hospital care for people after hip fracture surgery who have cognitive impairment: a feasibility cluster randomised controlled trial.

OBJECTIVES: Assess feasibility of a cluster randomised controlled trial (RCT) to measure clinical and cost-effectiveness of an enhanced recovery pathway for people with hip fracture and cognitive impairment (CI). DESIGN: Feasibility trial undertaken between 2016 and 2018. SETTING: Eleven acute hospitals from three UK regions. PARTICIPANTS: 284 participants (208 female:69 male). INCLUSION CRITERIA: aged >60 years, confirmed proximal hip fracture requiring surgical fixation and CI; preoperative AMTS ≤8 in England or a 4AT score ≥1 in Scotland; minimum of 5 days on study ward; a 'suitable informant' able to provide proxy measures, recruited within 7 days of hip fracture surgery. EXCLUSION CRITERIA: no hip surgery; not expected to survive beyond 4 weeks; already enrolled in a clinical trial. INTERVENTION: PERFECT-ER, an enhanced recovery pathway with 15 quality targets supported by a checklist and manual, a service improvement lead a process lead and implemented using a plan-do-study-act model. PRIMARY AND SECONDARY OUTCOME MEASURES: Feasibility outcomes: recruitment and attrition, intervention acceptability, completion of participant reported outcome measures, preliminary estimates of potential effectiveness using mortality, EQ-5D-5L, economic and clinical outcome scores. RESULTS: 282 participants were consented and recruited (132, intervention) from a target of 400. Mean recruitment rates were the same in intervention and control sites, (range: 1.2 and 2.7 participants/month). Retention was 230 (86%) at 1 month and 54%(144) at 6 months. At 3 months a relatively small effect (one quarter of an SD) was observed on health-related quality of life of the patient measured with EQ-5D-5L proxy in the intervention group. CONCLUSION: This trial design was feasible with modifications to recruitment. Mechanisms for delivering consistency in the PERFECT-ER intervention and participant retention need to be addressed. However, an RCT may be a suboptimal research design to evaluate this intervention due to the complexity of caring for people with CI after hip fracture. TRIAL REGISTRATION NUMBER: ISRCTN99336264.

Selective 5HT3 antagonists and sensory processing: a systematic review.

Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson's disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.

Neuropsychiatric symptoms in limbic-predominant age-related TDP-43 encephalopathy and Alzheimer's disease.

There is clinical overlap between presentations of dementia due to limbic-predominant age-related TDP-43 encephalopathy (LATE) and Alzheimer's disease. It has been suggested that the combination of Alzheimer's disease neuropathological change (ADNC) and LATE neuropathological changes (LATE-NC) is associated with greater neuropsychiatric symptom burden, compared to either pathology alone. Longitudinal Neuropsychiatric Inventory and psychotropic medication prescription data from neuropathologically diagnosed pure ADNC (n = 78), pure LATE-NC (n = 14) and mixed ADNC/LATE-NC (n = 39) brain bank donors were analysed using analysis of variance and linear mixed effects regression models to examine the relationship between diagnostic group and neuropsychiatric symptom burden. Nearly all donors had dementia; three (two pure LATE-NC and one pure ADNC) donors had mild cognitive impairment and another two donors with LATE-NC did not have dementia. The mixed ADNC/LATE-NC group was older than the pure ADNC group, had a higher proportion of females compared to the pure ADNC and LATE-NC groups, and had more severe dementia versus the pure LATE-NC group. After adjustment for length of follow-up, cognitive and demographic factors, mixed ADNC/LATE-NC was associated with lower total Neuropsychiatric Inventory and agitation factor scores than pure ADNC, and lower frontal factor scores than pure LATE-NC. Our findings indicate that concomitant LATE pathology in Alzheimer's disease is not associated with greater neuropsychiatric symptom burden. Future longitudinal studies are needed to further investigate whether mixed ADNC/LATE-NC may be protective against agitation and frontal symptoms in dementia caused by Alzheimer's disease or LATE pathology.

Impact of Biofuel Blends on Black Carbon Emissions from a Gas Turbine Engine.

Presented here is an overview of non-volatile particulate matter (nvPM) emissions, i.e. "soot" as assessed by TEM analyses of samples collected after the exhaust of a J-85 turbojet fueled with Jet-A as well as with blends of Jet-A and Camelina biofuel. A unifying explanation is provided to illustrate the combustion dynamics of biofuel and Jet-A fuel. The variation of primary particle size, aggregate size and nanostructure are analyzed as a function of biofuel blend across a range of engine thrust levels. The postulate is based on where fuels start along the soot formation pathway. Increasing biofuel content lowers aromatic concentration while placing increasing dependence upon fuel pyrolysis reactions to form the requisite concentration of aromatics for particle inception and growth. The required "kinetic" time for pyrolysis reactions to produce benzene and multi-ring PAHs allows increased fuel-air mixing by turbulence, diluting the fuel-rich soot-forming regions, effectively lowering their equivalence ratio. With a lower precursor concentration, particle inception is slowed, the resulting concentration of primary particles is lowered and smaller aggregates were measured. The lower equivalence ratio also results in smaller primary particles because of the lower concentration of growth species.

The Inverted Free Functioning Gracilis Muscle Transfer For Restoration of Elbow Flexion Following Delayed Presentation or Failed Primary Nerve Reconstruction of Upper Trunk Injuries.

Free functional gracilis transfer is a well-established technique for restoring active elbow flexion in brachial plexus injuries following delayed presentation or failed nerve reconstruction procedures. In cases of delayed presentation or failed nerve reconstruction following upper trunk injuries, the lower trunk intraplexal median and ulnar nerves are spared, thereby making them available to reinnervate the transferred gracilis. Therefore, we have inverted the conventional free functional gracilis orientation so as to orient the flap's recipient nerve in closer proximity to donor median or ulnar nerve fascicles to enable a short, tension-free coaptation in the middle to distal arm. Herein is our descriptive surgical technique for performing an inverted free functional gracilis muscle transfer in order to restore elbow flexion in the setting of an upper trunk injury.

Systematic review and meta-analysis of the association between peripheral inflammatory cytokines and generalised anxiety disorder.

OBJECTIVE: Inflammation has been implicated in the aetiology of mental illness. We conducted the first systematic review and meta-analysis of the association between peripheral markers of inflammation and generalised anxiety disorder (GAD). DESIGN: Systematic review and meta-analysis of studies measuring peripheral cytokine levels in people with GAD compared with controls. DATA SOURCES: MEDLINE (1950-), EMBASE (1947-), PsycINFO (1872-) and Web of Science (1945-) databases up until January 2018. ELIGIBILITY CRITERIA: Primary, quantitative research studies of people with a diagnosis of GAD assessed using a standardised clinical interview that measured peripheral inflammatory markers. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed study quality. Meta-analysis using a random-effects model was conducted for individual cytokines where data from three or more studies were available. RESULTS: 14 of 1718 identified studies met the inclusion criteria, comprising 1188 patients with GAD and 10 623 controls. In total 16 cytokines were evaluated. Significantly raised levels of C reactive protein (CRP), interferon-γ and tumour necrosis factor-α were reported in patients with GAD compared with controls in two or more studies. Ten further proinflammatory cytokines were reported to be significantly raised in GAD in at least one study. However, 5 of 14 studies found no difference in the levels of at least one cytokine. Only CRP studies reported sufficient data for meta-analysis. CRP was significantly higher in people with GAD compared with controls, with a small effect size (Cohen's d=0.38, 0.06-0.69), comparable with that reported in schizophrenia. However, heterogeneity was high (I2=75%), in keeping with meta-analyses of inflammation in other psychiatric conditions and reflecting differences in participant medication use, comorbid depression and cytokine sampling methodology. CONCLUSION: There is preliminary evidence to suggest an inflammatory response in GAD, but it remains unclear whether inflammatory cytokines play a role in the aetiology. GAD remains a poorly studied area of neuroinflammation compared with other mental disorders, and further longitudinal studies are required.

Identification of risk factors for arterial repair failures and lessons learned: Experiences from managing 129 combat vascular extremity wounds in the Sri Lankan War.

BACKGROUND: In extremity vascular trauma, early complications occur at a rate of 13% to 44%. The most common of which are infection, dehiscence, thrombosis, and stenosis. Failure of the arterial repair, also called arterial blowout, has the potential for exsanguinating hemorrhage and poses a considerable challenge for the surgeon to save limb and life. METHOD: All adults with extremity vascular injuries admitted in 8-month period were prospectively recorded and retrospectively analyzed. Extremity vascular injuries in this group include those in which limb salvage attempted. 5 arterial blowouts in a recorded 87 arterial repairs were analyzed for demographics, presentation, management and outcome in the context of identifying most probable causative factors. RESULT: 5 arterial blowouts occurred out of 87 arterial repairs for a rate of 5.75%. These occurred at a mean of 14 days post-operatively. All patients were male with the majority of the injuries, 80%, resulting from gunshot wounds. All injuries were associated with severe soft tissue injury and clinical evidence of bacterial infection. Technical error, inadequate debridement, prolonged exposed vessel and unstable skeletal injury were noted as causative factors in addition to the commonly reported causes of repair failure. At a mean follow-up of 17 days, the arterial blowout cohort had 80% limb survival rate. CONCLUSION: Ischemic, damaged and contaminated military wounds lead to infections of varied degree. Delay in closure due to tight distal muscle compartments or severe persistent soft tissue infections, necessitating serial irrigation and debridement (I&D) of wounds, is the common chain noted leading to arterial blowout. To break this chain of events the authors suggest early identification of at risk limbs and aggressive soft tissue cover of the newly constructed repair. LEVEL OF EVIDENCE: Case series, level IV.

Amisulpride for very late-onset schizophrenia-like psychosis: the ATLAS three-arm RCT.

BACKGROUND: Very late-onset (aged ≥ 60 years) schizophrenia-like psychosis (VLOSLP) occurs frequently but no placebo-controlled, randomised trials have assessed the efficacy or risks of antipsychotic treatment. Most patients are not prescribed treatment. OBJECTIVES: The study investigated whether or not low-dose amisulpride is superior to placebo in reducing psychosis symptoms over 12 weeks and if any benefit is maintained by continuing treatment thereafter. Treatment safety and cost-effectiveness were also investigated. DESIGN: Three-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial. Participants who received at least one dose of study treatment were included in the intention-to-treat analyses. SETTING: Secondary care specialist old age psychiatry services in 25 NHS mental health trusts in England and Scotland. PARTICIPANTS: Patients meeting diagnostic criteria for VLOSLP and scoring > 30 points on the Brief Psychiatric Rating Scale (BPRS). INTERVENTION: Participants were randomly assigned to three arms in a two-stage trial: (1) 100 mg of amisulpride in both stages, (2) amisulpride then placebo and (3) placebo then amisulpride. Treatment duration was 12 weeks in stage 1 and 24 weeks (later reduced to 12) in stage 2. Participants, investigators and outcome assessors were blind to treatment allocation. MAIN OUTCOME MEASURES: Primary outcomes were psychosis symptoms assessed by the BPRS and trial treatment discontinuation for non-efficacy. Secondary outcomes were extrapyramidal symptoms measured with the Simpson-Angus Scale, quality of life measured with the World Health Organization's quality-of-life scale, and cost-effectiveness measured with NHS, social care and carer work loss costs and EuroQol-5 Dimensions. RESULTS: A total of 101 participants were randomised. Ninety-two (91%) participants took the trial medication, 59 (64%) completed stage 1 and 33 (56%) completed stage 2 treatment. Despite suboptimal compliance, improvements in BPRS scores at 12 weeks were 7.7 points (95% CI 3.8 to 11.5 points) greater with amisulpride than with placebo (11.9 vs. 4.2 points; p = 0.0002). In stage 2, BPRS scores improved by 1.1 point in those who continued with amisulpride but deteriorated by 5.2 points in those who switched from amisulpride to placebo, a difference of 6.3 points (95% CI 0.9 to 11.7 points; p = 0.024). Fewer participants allocated to the amisulpride group stopped treatment because of non-efficacy in stages 1 (p = 0.01) and 2 (p = 0.031). The number of patients stopping because of extrapyramidal symptoms and other side effects did not differ significantly between groups. Amisulpride treatment in the base-case analyses was associated with non-significant reductions in combined NHS, social care and unpaid carer costs and non-significant reductions in quality-adjusted life-years (QALYs) in both stages. Including patients who were intensive users of inpatient services in sensitivity analyses did not change the QALY result but resulted in placebo dominance in stage 1 and significant reductions in NHS/social care (95% CI -£8923 to -£122) and societal costs (95% CI -£8985 to -£153) for those continuing with amisulpride. LIMITATIONS: The original recruitment target of 300 participants was not achieved and compliance with trial medication was highly variable. CONCLUSIONS: Low-dose amisulpride is effective and well tolerated as a treatment for VLOSLP, with benefits maintained by prolonging treatment. Potential adverse events include clinically significant extrapyramidal symptoms and falls. FUTURE WORK: Trials should examine the longer-term effectiveness and safety of antipsychotic treatment in this patient group, and assess interventions to improve their appreciation of potential benefits of antipsychotic treatment and compliance with prescribed medication. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45593573 and EudraCT2010-022184-35. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 67. See the NIHR Journals Library website for further project information.

An anatomic transcriptional atlas of human glioblastoma.

Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor's molecular and cellular landscapes are complex, and their relationships to histologic features routinely used for diagnosis are unclear. We present the Ivy Glioblastoma Atlas, an anatomically based transcriptional atlas of human glioblastoma that aligns individual histologic features with genomic alterations and gene expression patterns, thus assigning molecular information to the most important morphologic hallmarks of the tumor. The atlas and its clinical and genomic database are freely accessible online data resources that will serve as a valuable platform for future investigations of glioblastoma pathogenesis, diagnosis, and treatment.

TNF alpha inhibitors in Alzheimer's disease: A systematic review.

OBJECTIVES: The objective of this study was to evaluate the effect of tumour necrosis factor-alpha inhibitors (TNF-αI) on Alzheimer's disease-associated pathology. DESIGN: A literature search of PubMed, Embase, PsychINFO, Web of Science, Scopus, and the Cochrane Library databases for human and animal studies that evaluated the use of TNF-αI was performed on 26 October 2016. RESULTS: The main outcomes assessed were cognition and behaviour, reduction in brain tissue mass, presence of plaques and tangles, and synaptic function. Risk of bias was assessed regarding blinding, statistical model, outcome reporting, and other biases. Sixteen studies were included, 13 of which were animal studies and 3 of which were human. All animal studies found that treatment with TNF-αI leads to an improvement in cognition and behaviour. None of the studies measured change in brain tissue mass. The majority of studies documented a beneficial effect in other areas, including the presence of plaques and tangles and synaptic function. The amount of data from human studies was limited. Two out of 3 studies concluded that TNF-αI are beneficial in Alzheimer's disease patients, with one being an observational study and the latter being a small pilot study, with a high risk of bias. CONCLUSION: It was concluded that a large-scale randomized controlled trial assessing the effectiveness of TNF-αI on humans is warranted.

Effect of Biofuels on Biodegradation of Benzene and Toluene at Gasoline Spill Sites.

The risk that benzene and toluene from spills of gasoline will impact drinking water wells is largely controlled by the natural anaerobic biodegradation of benzene and toluene. Benzene and toluene, as well as ethanol and other biofuels, are degraded under anaerobic conditions to the same pool of degradation products. Biodegradation of biofuels may produce concentrations of degradation products that make the thermodynamics for degradation of benzene and toluene infeasible under methanogenic conditions and produce larger plumes of benzene and toluene. This study evaluated the concentrations of fuel alcohols that are necessary to inhibit the anaerobic degradation of benzene and toluene under methanogenic conditions. At two ethanol spill sites, concentrations of ethanol greater ≥42 mg/L inhibited the anaerobic degradation of toluene. The pH and concentrations of acetate, dissolved inorganic carbon, and molecular hydrogen were used to calculate the Gibbs free energy for the biodegradation of toluene. In general, the anaerobic biodegradation of toluene was not thermodynamically feasible in water with ≥42 mg/L ethanol. In a microcosm study, when the concentrations of ethanol were ≥14 mg/L or the concentrations of n-butanol were ≥16 mg/L, the biodegradation of the alcohols consistently produced concentrations of hydrogen, dissolved inorganic carbon, and acetate that would preclude natural anaerobic biodegradation of benzene and toluene by syntrophic organisms. In contrast, iso-butanol and n-propanol only occasionally produced conditions that would preclude the biodegradation of benzene and toluene.

Use of intraoperative fluorescent angiography to assess and optimize free tissue transfer in head and neck reconstruction.

PURPOSE: Composite tissue defects in the head and neck region present unique challenges. Definitive head and neck reconstruction of these cases is often complicated by complex 3-dimensional defects that may require multiple flap or chimeric flap procedures. These advanced techniques can have serious repercussions should poor perfusion of the flap cause flap failure, which can be devastating. MATERIALS AND METHODS: A retrospective review was completed for those complex reconstructions using free tissue transfers and fluorescent indocyanine green angiography (Lifecell SPY Elite imaging, Lifecell Corporation, Bridgewater, NJ) at Walter Reed National Military Medical Center over a 24-month period. Data analyzed included flap type (myocutaneous, osteocutaneous, or fasciocutaneous), flap success and failure rates, and complications. These also were compared with data from the institution before the study period and the incorporation of SPY technology. RESULTS: Sixty-one free flaps, including 11 head and neck flaps, were performed. The head and neck flaps included 1 latissimus, 3 gracilis, 1 vastus lateralis, 4 anterior lateral thigh, and 2 fibular flaps. The overall success rate was 98.4%; 1 flap was lost (1.6%) and 2 flaps developed partial flap necrosis (3.3%). Where SPY Elite was used, there was no unpredicted partial flap necrosis. The only total flap loss was related to a hypercoagulable condition. CONCLUSIONS: Free tissue transfer can be technically challenging, especially in complex head and neck reconstruction. An algorithmic approach using SPY Elite imaging aids in pedicle location, angiosomal assessment, anastomotic flow visualization, and cutaneous and osteocutaneous flap perfusion assessment. This objective tool can assist the reconstructive surgeon in avoiding perfusion-related complications and total and partial flap losses, thus improving patient outcomes.

Soft tissue injury management with a continuous external tissue expander.

BACKGROUND: Blast exposure is a common cause of soft tissue injury within the battlefield setting, with the extremities often critically involved. The resulting injury pattern presents with massive soft tissue defects that may be further complicated by varying degrees of accompanying orthopedic and peripheral nerve damage. To address the severe soft tissue defect, various combinations of advanced reconstructive methods are typically required to achieve definitive wound coverage. Continuous external tissue expansion has been used by our institution to significantly reduce wound burden and provide for definitive wound closure in certain blast-injured patients. METHODS: The authors present an early series of 14 patients who suffered massive extremity soft tissue injuries and were treated with an external tissue expansion system (DermaClose RC). Outcome measurements included time to definitive closure and method of definitive wound closure. A 5-patient subset of this group was prospectively analyzed to determine measurements including initial wound surface area (WSA), percentage reduction in WSA, and related complications. RESULTS: Overall time to wound coverage ranged from 1 to 6 days, with mean time to wound coverage being 4.4 days. Of the 14 patients included in the series, 12 (85.7%) were able to undergo delayed primary closure, whereas 2 required split thickness skin grafting. In the 5-patient subgroup, WSA initially ranged from 20.25 to 1031.25 cm2. Mean wound size was 262.7 cm2. Decrease in WSA ranged from 44% to 93% of the initial WSA, with mean decrease being 74.3% (95% confidence interval, 57.33-91.3). CONCLUSIONS: In the management of large complex wounds, external tissue expansion has proven to be a valuable adjunct in achieving definitive wound closure. It can often aid in successful delayed primary closure of certain soft tissue wounds, has low associated morbidities, and can reduce the need for more complex or morbid procedures when used properly. The authors propose an algorithm for the use of continuous external tissue expansion system to achieve effective and successful wound closure, while potentially reducing the need for increased donor-site morbidities associated with more complex or larger reconstruction measures.

Computer-assisted reduction method for periprosthetic distal femur fracture.

The purpose of this case report is to describe a novel use of computer assistance in identifying and restoring the mechanical axis in the treatment of a periprosthetic distal femur fracture in a 76-year-old female patient with a total knee arthroplasty.

Successful knee extensor mechanism reconstruction in a warfare-related open lower extremity injury complicated by mucormycosis infection: a case report.

Subcutaneous zygomycosis infection associated with a lower extremity open fracture is a potentially life- and limb-threatening condition. This rare and poorly characterized infection complicating war wounds is unique, complex, and poses a significant reconstructive challenge. The objective of this article is to report the reconstruction of a complex Gustilo IIIC warfare-related distal femur fracture with partial extensor mechanism loss complicated by a subcutaneous zygomycosis infection using a novel combination of local and systemic antifungals with negative pressure wound therapy. Negative pressure wound therapy with silver-impregnated sponges and antibiotic/antifungal beads was used to provide temporary wound coverage, improve revascularization, and deliver local antifungal therapy. The distal open femur fracture was fixed using a lateral approach and the medial distal thigh wound and extensor mechanism were reconstructed using an extended gastrocnemius flap with skin graft. The limb was successfully salvaged and the patient is now ambulatory.

Globe rupture with post cataract-surgery safety sunglasses.

UNLABELLED: We report a case of globe rupture associated with the use of post cataract-surgery protective eyewear. The patient had routine cataract surgery 3 months before presentation and had adapted his post cataract-surgery glasses to use on the tennis court. He experienced a large posterior globe rupture after falling directly onto his face during a match. Spectacle torsion is the suspected biomechanical process that led to the rupture. We conclude that although the glasses given to many patients after cataract surgery are protective for most low-impact injuries, patients should be aware they are not designed for activities with a risk for significant impact. Patients should also be counseled to use protective eyewear specifically designed and approved for the sport or activity in which they participate. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Progressive Gorham disease of the forearm.

Gorham's-Stout disease is a rare but potentially debilitating disease consisting of massive bone osteolysis and bone resorption associated with vascular proliferation and increased osteoclastic activity. Although it can present in a wide variety of forms, it typically involves bones formed by intramembranous ossification such as the skull, pelvis, and scapula. It can occur spontaneously or after trauma. Most cases are monofocal and resolved spontaneously, although there are reports of multifocal and rapidly progressing disease. It typically presents as disuse muscle atrophy or pathologic fracture during the second through fourth decades of life, yet it has also been reported in childhood and in the elderly. The etiology of Gorham's disease remains to be fully elucidated. Gorham attributed the origin of the disease to uncontrolled proliferation of small vessels eating away bone tissue. Other authors attribute the cause of the disease to increased osteoclastic activity mediated by elevated cytokine levels and increased osteoclastic differentiation. Treatment is not established and focuses at stopping osteoclastic activity and angiogenic proliferation. Radiation therapy, chemotherapy, bone grafting, and antiresorptives medications have all been used with different degrees of success. In an effort to further characterize this elusive disease, we report on an unusual presentation of a patient with Gorham's disease of the radius spreading to the ulna and then the proximal humerus with a 13-year follow-up. To our knowledge this is the first report in the literature of a saltatory type of Gorham's disease spreading from bone to bone across a joint.

Embryonic stem cell-derived motor neurons preserve muscle after peripheral nerve injury.

BACKGROUND: The potential of motor neuron progenitor cell transplants to preserve muscle tissue after denervation was studied in in vivo and in vitro adult mammalian model of peripheral nerve injury. METHODS: Embryonic stem cells were differentiated to induce cholinergic motor neuron progenitors. Flourescent-labeled progenitor cells were injected into the gastrocnemius muscle of Sprague-Dawley rats (n = 10) after denervation by ipilateral sciatic nerve transection. Control rats received injections of either a phosphate-buffered saline solution only (n = 12), murine embryonic fibroblast (STO) cells (n= 6), or undifferentiated embryonic stem cells (n= 6). Muscles were weighed and analyzed at 7 and 21 days using histology, histomorphometry, and immunostaining. RESULTS: Seven days after progenitor cell transplant, both muscle mass and myocyte cross-sectional area were preserved, compared with control muscles, which demonstrated muscle mass reduction to 70 percent and reduction of cross-sectional area to 72 percent of normal. Fluorescent microscopy of transplanted muscles confirmed the presence of motor neuron progenitors. Presynaptic neuronal staining of the transplants overlapped with alpha-bungarotoxin-labeled muscle fibers, revealing the presence of new neuromuscular junctions. By 21 days, muscle atrophy in the experimental muscles was equal to that of controls and no transplanted cells were observed. Co-culture of the motor neuron progenitor cells and myocytes also demonstrated new neuromuscular junctions by immunofluorescence. CONCLUSIONS: Transplanted motor neuron progenitors prevent muscle atrophy after denervation for a brief time. These progenitor cell transplants appear to form new neuromuscular junctions with denervated muscle fibers in vivo and with myocytes in vitro.