Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity.

We present clinicopathologic data on 10 pulmonary myxoid sarcomas, which are defined by distinctive histomorphologic features and characterized by a recurrent fusion gene, that appear to represent a distinct tumor entity at this site. The patients [7 female, 3 male; aged 27 to 67 y (mean, 45 y)] presented with local or systemic symptoms (n=5), symptoms from cerebral metastasis (1), or incidentally (2). Follow-up of 6 patients showed that 1 with brain metastasis died shortly after primary tumor resection, 1 developed a renal metastasis but is alive and well, and 4 are disease free after 1 to 15 years. All tumors involved pulmonary parenchyma, with a predominant endobronchial component in 8 and ranged from 1.5 to 4 cm. Microscopically, they were lobulated and composed of cords of polygonal, spindle, or stellate cells within myxoid stroma, morphologically reminiscent of extraskeletal myxoid chondrosarcoma. Four cases showed no or minimal atypia, 6 showed focal pleomorphism, and 5 had necrosis. Mitotic indices varied, with most tumors not exceeding 5/10 high-power fields. Tumors were immunoreactive for only vimentin and weakly focal for epithelial membrane antigen. Of 9 tumors, 7 were shown to harbor a specific EWSR1-CREB1 fusion by reverse transcription-polymerase chain reaction and direct sequencing, with 7 of 10 showing EWSR1 rearrangement by fluorescence in situ hybridization. This gene fusion has been described previously in 2 histologically and behaviorally different sarcomas: clear cell sarcoma-like tumors of the gastrointestinal tract and angiomatoid fibrous histiocytomas; however, this is a novel finding in tumors with the morphology we describe and that occur in the pulmonary region.

Use of physiotherapy and alternatives by children with cerebral palsy: a population study

Objectives: To describe the use of physiotherapy services and alternative therapies by a population of children with moderate to severe cerebral palsy (CP).
Design: Descriptive cross-sectional survey.
Subjects: A total of 212 parents of children aged 4–14 years with moderate to severe CP were identified from the Northern Ireland Cerebral Palsy Register (NICPR) and a random subsample of their paediatric physiotherapists.
Main measures: A standardized description of motor impairment or assessment form; a postal questionnaire to parents and paediatric physiotherapists (to validate parents’ reports of service use).
Response rates: In total, 85% of parent questionnaires were returned and 100% of paediatric physiotherapists responded.
Results: Service use among families was high; on average the families had contact with approximately seven services in a 6-month time interval. The overwhelming majority of children (96%) received physiotherapy during the school term and most (59%) received treatment at least twice a week for 30 min; 43% of children had their physiotherapy discontinued over the summer holidays. Over one-quarter (28%) of families had opted out of the NHS and bought alternatives like conductive education (21%) or private forms of conventional physiotherapy (16%). Children with more severe forms of CP, in special education, particularly at schools for physical disability, were high-intensity users of the physiotherapy service. Despite this, 74% of parents wanted more physiotherapy for their child.
Conclusions and implications: The demand for physiotherapy services is likely to continue given the relatively stable prevalence rate of CP, the proportion of children with disabling CP and the level of parent interest in the service. A number of quality aspects and gaps in the service have been identified.

Making doors open: caring for families of children with severe cerebral palsy

Cerebral palsy is a relatively rare condition affecting approximately 2-2.5 children in every 1,000 (Parkes et al 2001). It is a leading cause of physical disability in childhood and is often associated with severe motor and other impairments (Table 1). Improved survival of small and premature babies who are particularly at risk of developing the condition raises concerns about increasing numbers of children with cerebral palsy possibly with more severe forms. In the UK, information about the number and needs of children with CP is not collected routinely. The most reliable sources of information on CP in the UK comes from five dedicated case registers which have monitored live births in their respective geographically defined areas since the 1960s and 1970s. These registers have formed a collaborative network called the United Kingdom Collaboration of Cerebral Palsy Registers (or UKCP) and are listed in Table 2. All five registers are currently funded and all are active in surveillance activities and research.

Trends in the prevalence of cerebral palsy in Northern Ireland, 1981-1997

We describe trends in the prevalence of cerebral palsy (CP) by birth weight group, and in the severity of motor impairments and presence of associated intellectual impairment, in Northern Ireland from 1981 to 1997 (n=909; 510 males, 399 females; total population 415 936 live births) using data from a population-based register of CP. Children with suspected CP or who died before 1 year of age and those with CP of postneonatal origin were excluded. Prevalence of CP was 2.2 per 1000 live births without significant change over time. Among very-low-birthweight (<1500g) live births, prevalence was 44.5 per 1000 (95% confidence interval 32.3–59.8) from 1994 to 1997, with evidence of a statistically significant decline in prevalence since the mid- to late 1980s accompanied by a decrease in the severity of motor impairment and likelihood of intellectual impairment. Among moderately-low-birthweight (1500–2499g) children there was weaker evidence of a peak prevalence in the late 1980s. Prevalence among normal-birthweight infants did not change significantly, but outcome in terms of severity of motor impairment and intellectual impairment improved in the 1990s. Occurrence of bilateral spasticity from 1994 to 1997 was associated with greater severity and likelihood of intellectual impairment for normal-birthweight individuals than for low- or very-low-birth weight individuals.

Ectopic ACTH-syndrome due to a thymic carcinoid tumor

Investigating a recently developed Cushing Syndrome, we diagnosed in a 47-year-old woman an ectopic ACTH syndrome due to a metastatic carcinoid tumor, most likely a thymic carcinoid tumor. Combined therapy with sandostatin and nizoral and later on with sandostatin, metopirone and orimeten, was not able to suppress the hypercortisolism. A few weeks after surgical adrenalectomy, clinical deterioration ensued, culminating in the patient's death 7 months after diagnosis.

Accommodative dysfunction in children with cerebral palsy: a population based study

Purpose. To determine the prevalence, nature, and degree of accommodative dysfunction among children with different types and severities of cerebral palsy (CP) in Northern Ireland. Methods. Ninety subjects with CP (aged 4–15 years) were recruited through the Northern Ireland CP Register (NICPR). Modified Nott dynamic retinoscopy was used to measure lag and lead of accommodation at three test distances: 25 cm (4 D), 16.7 cm (6 D), and 10 cm (10 D) with the distance correction in place. Accommodative function was also assessed in an age-matched control group (n = 125) for comparison. Each subject’s neurologic status was derived from the NICPR. Results. Children with CP demonstrate significantly reduced accommodative responses compared with their neurologically normal peers. Of the subjects with CP, 57.6% demonstrated an accommodative lag outside normal limits at one or more distances. Reduced accommodative responses were significantly associated with more severe motor and intellectual impairments (ANOVA P = 0.001, P < 0.01, respectively). Conclusions. Brain injury such as that present in CP has a significant impact on accommodative function. These findings have implications for the optometric care of children with CP and inform our understanding of the impact of early brain injury on visual development.

Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy

The present study was undertaken to test whether inhibition of the proangiogenic inflammatory cytokine tumor necrosis factor (TNF)-alpha can modulate retinal hypoxia and preretinal neovascularization in a murine model of oxygen-induced retinopathy (OIR). OIR was produced in TNF-alpha-/- and wild-type (WT) control C57B6 neonatal mice by exposure to 75% oxygen between postnatal days 7 and 12 (P7 to P12). Half of each WT litter was treated with the cytokine inhibitor semapimod (formerly known as CNI-1493) (5 mg/kg) by daily intraperitoneal injection from the time of reintroduction to room air at P12 until P17. The extent of preretinal neovascularization and intraretinal revascularization was quantified by image analysis of retinal flat-mounts and retinal hypoxia correlated with vascularization by immunofluorescent localization of the hypoxia-sensitive drug pimonidazole (hypoxyprobe, HP). HP adducts were also characterized by Western analysis and quantified by competitive enzyme-linked immunosorbent assay. TNF-alpha-/- and WT mice showed a similar sensitivity to hyperoxia-induced retinal ischemia at P12. At P13 some delay in early reperfusion was evident in TNFalpha-/- and WT mice treated with semapimod. However, at P17 both these groups had significantly better vascular recovery with less ischemic/hypoxic retina and preretinal neovascularization compared to untreated retinopathy in WT mice. Immunohistochemistry showed deposition of HP in the avascular inner retina but not in areas underlying preretinal neovascularization, indicating that such aberrant vasculature can reduce retinal hypoxia. Inhibition of TNF-alpha significantly, improves vascular recovery within ischemic tissue and reduces pathological neovascularization in OIR. HP provides a useful tool for mapping and quantifying tissue hypoxia in experimental ischemic retinopathy.