A qualitative analysis of the benefits of strength training for young people with cerebral palsy

This qualitative study investigated the positive and negative outcomes of a home-based strength-training programme for young people with cerebral palsy (CP). Eleven young people with spastic diplegic CP (seven females, four males; mean age 12 years 9 months, SD 2 years 10 months; range 8 to 18 years) and their parents were interviewed. Gross Motor Function Classification System scores ranged from I (walks without limitations) to III (walks with assistive device), with a mode of III. The strength-training programme, which was conducted in the participants' homes three times per week for 6 weeks (total of 18 prescribed sessions), comprised three exercises targeting the major support muscles of the lower limbs. Exercises were bilateral half squats, heel raises, and step-ups. The training load was increased by adding free weights to a backpack so that 8 to 10 repetitions of each exercise could be performed. Using thematic coding, three categories of outcome emerged: body function and structure, activity, and participation, which were influenced by environmental and personal contextual factors. The programme generated overwhelmingly positive outcomes with only minor negative responses about some equipment and the need for parental involvement. Benefits included perceptions that strength, flexibility, posture, walking, and the ability to negotiate steps had improved. In addition, participants reported psychological benefits such as a feeling of increased well-being and improved participation in school and leisure activities. The contextual factors highlighted the fact that sufficient clinician resources must be allocated to solve individual exercise and equipment problems. As well as providing further evidence that strength training can be beneficial, this study provides useful indicators to guide future quantitative studies of outcomes that are meaningful for people with CP.     

Conjunctival squamous cell carcinoma with perineural invasion resulting in death.

Conjunctival squamous cell carcinoma is generally a low-grade malignancy. A 42-year-old man presented with histologic evidence of extra-tumoral perineural invasion associated with an incompletely excised limbal conjunctival squamous cell carcinoma. Despite further surgery, close observation, plaque radiotherapy, and eyelid-sparing orbital exenteration followed by external beam radiotherapy, the patient developed intracranial perineural invasion with involvement of the trigeminal and facial nerves, ultimately resulting in death. Repeated magnetic resonance imaging with contrast failed to detect perineural invasion until late in the course of disease. Awareness of the possibility of perineural invasion in patients with conjunctival squamous cell carcinoma and of its aggressive nature may be life-saving. Nevertheless, even with initial aggressive tumor control, some patients will show an aggressive tumor growth with recurrences.     

Genes involved in DNA repair and nitrosamine metabolism and those located on chromosome 14q32 are dysregulated in nasopharyngeal carcinoma.

Polymorphisms in nitrosamine metabolism, DNA repair, and immune response genes have been associated with nasopharyngeal carcinoma (NPC). Studies have suggested chromosomal regions involved in NPC. To shed light on NPC etiology, we evaluated host gene expression patterns in 31 NPC and 10 normal nasopharyngeal tissue specimens using the Affymetrix Human Genome U133 Plus 2.0 Array. We focused on genes in five a priori biological pathways and chromosomal locations. Rates of differential expression within these prespecified lists and overall were tested using a bootstrap method. Differential expression was observed for 7.6% of probe sets overall. Elevations in rate of differential expression were observed within the DNA repair (13.7%; P = 0.01) and nitrosamine metabolism (17.5%; P = 0.04) pathways. Differentially expressed probe sets within the DNA repair pathway were consistently overexpressed (93%), with strong effects observed for PRKDC, PCNA, and CHEK1. Differentially expressed probe sets within the nitrosamine metabolism pathway were consistently underexpressed (100%), with strong effects observed for NQ01, CYP2B6, and CYP2E1. No significant evidence of increases in rate of differential expression was seen within the immune/inflammatory pathway. A significant elevation in rate of differential expression was noted for chromosome 4p15.1-4q12 (13.0%; P = 0.04); both overexpression and underexpression were evident (38% and 62%, respectively). An elevation in the rate of differential expression on chromosome 14q32 was observed (11.3%; P = 0.06) with a consistent pattern of gene underexpression (100%; P < 0.0001). These effects were similar when excluding late-stage tumors. Our results suggest that nitrosamine activation and DNA repair are important in NPC. The consistent down-regulation of expression on chromosome 14q32 suggests loss of heterozygosity in this region.     

Radiofrequency thermal ablation: computer analysis of the size of the thermal injury created by overlapping ablations

OBJECTIVE: The purpose of this study was to perform a computer analysis of the size of the thermal injury created by overlapping multiple thermal ablation spheres. MATERIALS AND METHODS: A computer-assisted design system was used to create three-dimensional models of a spherical tumor, a spherical tissue volume consisting of the tumor plus a 1-cm tumor-free margin, and individual spherical ablations. These volumes were superimposed in real-time three-dimensional space in different geometric relationships. The effect of the size and geometric configuration of the ablation spheres was analyzed with regard to the ability to ablate the required volume of tissue (tumor plus margin) without leaving untreated areas or interstices. RESULTS: The single-ablation model showed that if a 360-degree 1-cm tumor-free margin is included around the tumor targeted for ablation, radiofrequency ablation devices producing 3-, 4-, and 5-cm ablation spheres can be used to treat 1-, 2-, and 3-cm tumors, respectively. The six-sphere model, in which six ablation spheres are placed in orthogonal planes around the tumor, showed that the largest tumor that may be treated with a 3-cm ablation device is 1.75 cm, whereas 4- and 5-cm ablation spheres can be used to treat tumors measuring 3 and 4.25 cm, respectively. The 14- sphere model showed that addition of eight more spheres to the six-sphere model increased the treatable tumor size to 3, 4.6, or 6.3 cm, depending on the diameter of the ablation sphere used. For treating larger tumors, we found a cylindrical model to be less efficient but easier to control. CONCLUSION: Our computer analysis showed that the size of the composite thermal injury created by overlapping multiple thermal ablation spheres is surprisingly small relative to the number of ablations performed. These results emphasize the need for a methodic tumor ablation strategy.     

Outcome of preterm infants with congenital heart disease

OBJECTIVES AND STUDY DESIGN: To evaluate the morbidity and mortality of preterm infants with congenital heart disease (CHD), a chart review was performed for infants with CHD, excluding isolated patent ductus arteriosus, who were <37 weeks' gestation, weighed <2500 g, and were admitted to our neonatal intensive care unit from 1976 to 1999 (N = 201). RESULTS: Patients in the study represented 1.9% of the total neonatal intensive care unit population <37 weeks' gestation and <2500 g. The median gestational age was 33 weeks, and the mean birth weight was 1852 g. CHD diagnosis frequencies were similar to those reported in other large incidence studies, except for a higher percentage of conotruncal defects. The risk of necrotizing enterocolitis was 1.7 times higher and the overall mortality twice as high in our patients compared with patients in the neonatal intensive care unit who did not have CHD. Cardiac surgery (n = 133) was performed on 108 patients. During the recent period of 1985 to 1999, compared with our institution's overall results for CHD surgery, the operative mortality rate was 10.4% versus 5.4% for closed procedures and 25.4% versus 10.5% for open procedures. The actuarial survival rate is 51% at 10 years; survival improved as the study period progressed. CONCLUSIONS: Infants with both CHD and prematurity did significantly worse than either group alone. Such outcome data are required for proper allocation of resources to care for this high-risk pediatric population.     

Variations in the low levels of cyclin D1/BCL1 have prognostic value in chronic lymphocytic leukemia

Cyclin D1 (CyD1)/BCL1 (PRAD1) is expressed at high levels in almost all cases of mantle cell leukemia/lymphoma (MCL) and in rare cases of chronic lymphocytic leukemia (CLL). The CyD1/BCL1 protein plays an important role in the progression of cells through the G1 phase of cell cycle. Most of the CyD1/BCL1 protein expression studies are performed using immunohistochemistry. We used a sensitive solid-phase radioimmunoassay (RIA) to quantify CyD1 protein expression in 199 patients with CLL. Of these 137 patients were previously untreated with the rest having had standard chemotherapeutic regimens including alkylating agents and fludarabine before being referred to our center. Median white cell count in these patients was 49x10(3) /microl (range 3.0-438.5x10(3)/microl), hemoglobin level 13.1 g/dl (range 5.2-17.3 g/dl), platelet count 157x10(3) /microl (range 10-377x10(3) /microl), age 58 (range 26-89), and beta2-microglobulin 2.75 mg/dl (range 1.1-14.3). The median radioactivity (CPM) of mononuclear cells obtained from 56 normal individuals was assigned a value of 1. There was no significant variation in CyD1 levels among normal individuals (SD=0. 12). While most CyD1 levels in MCL varied from 6.5 to 15.6, the median CyD1/BCL1 in CLL was 1.4 with 75th percentile under 2.12. Rare CLL cases (3.5%) showed levels between 4 and 8.83. When divided into two groups at the median level, patients with higher CyD1/BCL1 expression had shorter survival (P = 0.03). This remained true when applied only to the previously untreated patients (P=0.05). Despite the relatively low expression, the CyD1/BCL1 levels in univariate analysis were as good or better predictors of survival than Binet (P = 0.03) or Rai (P = 0.05) staging. Furthermore, CyD1/BCL1 levels correlated with serum beta2-microglobulin (P = 0.001), white blood cell count (P = 0.004) and hemoglobin levels at the time of collection (P = 0.0003) but not with lymphocyte count, platelet count or age. The data demonstrate that CyD1/BCL1 is likely to play a significant role in the biology of CLL and can be used as a prognostic indicator. Further studies to clarify the role of CyD1 in the biology of CLL and its value as a prognostic indicator at the time of diagnosis are encouraged.     

A comparison of the spread of three formulations of botulinum neurotoxin A as determined by effects on muscle function

The purpose of these experiments was to compare the spread of three formulations of botulinum neurotoxin A. A gelatin/phosphate buffer (C), Dysport^R (D {0.5 U}, Botox^R (B {0.167 U}), or a purified preparation of botulinum neurotoxin A [Bont A] (BA {0.5 U}) was injected into the tibialis anterior of male, Wistar rats. After 4 days, the adjacent extensor digitorum longus muscle was isolated in situ and the nerve was maximally stimulated to determine contractile properties and the rate of fatigue. There were no differences in body or muscle weights between any of the groups after 4 days of treatment. Maximal twitch and tetanic tensions were decreased ≈ 25% ( p < 0.05) in all treatment groups compared to C. In addition, rate of tension development was significantly less in all treatment groups compared to C but one-half relaxation time and time to peak tension were not different between any groups. Fatigue of the muscle was significantly faster in all groups compared to C but there was no difference between treatment groups. These data indicated that botulinum toxin A injected intramuscularly was likely to spread to adjacent muscles but that the spread was not different between the three formulations tested. The effect of the spread ranged from a slight to a severe reduction in maximal tension but this did not occur in all animals studied.