Market testing. What am I bid?

Walsall's experience of marketing testing for urology services was that it is a difficult, time-consuming but thoroughly worthwhile process. We believe that a much improved level of service will be available to Walsall residents, representing excellent value for money. Turning the spotlight on to this particular specialty resulted in local provider trusts showing increased willingness to address the clinical management and quality issues about which the HA had expressed concern.     

Hypersensitivity to DNA-damaging agents in cultured cells from patients with Usher''s syndrome and Duchenne muscular dystrophy.

Lymphoblastoid lines from nine Usher's syndrome (recessively inherited retinitis pigmentosa and congenital sensorineural deafness) patients (representing eight kindreds) and from ten Duchenne muscular dystrophy patients (representing seven kindreds) showed a small but statistically significant hypersensitivity to the lethal effects of X-rays, as measured by the cellular ability to exclude the vital dye trypan blue, when compared with lines from 26 normal control subjects. Fibroblast lines from the Usher's syndrome patients, treated with X-rays or the radiomimetic, DNA-damaging chemical N-methyl-N'-nitro-N-nitrosoguanidine, also showed a statistically significant hypersensitivity when compared to normal fibroblast lines. These findings are consistent with the possibility that defective DNA repair mechanisms may be involved in the pathogenesis of these degenerative diseases.     

Extracorporeal irradiation for malignant bone tumors

PURPOSE: Extracorporeal irradiation (ECI) has been used selectively in the management of primary malignant bone tumors since 1996. We report our techniques for ECI and the short-term oncologic and orthopedic outcomes. METHODS AND MATERIALS: Sixteen patients with primary malignant bone tumors were treated with ECI from 1996 to 2000. The median age was 14 years. The histologic diagnoses were Ewing's sarcoma (11), osteosarcoma (4) and chondrosarcoma (1). The treated sites were femur (7), tibia (4), humerus (2), ilium (2), and sacrum (1). Following induction chemotherapy in Ewing's sarcomas and osteosarcoma, en bloc resection of the tumor and tumor-bearing bone was performed. A single dose of 50 Gy was delivered to the bone extracorporeally using either a linear accelerator (9 cases) or a blood product irradiator (7 cases). The orthopedic outcome was recorded using a standard functional scale. RESULTS: At a median follow-up of 19.5 months, there were no cases of local recurrence or graft failure. One patient required amputation due to chronic osteomyelitis. For the 10 patients with follow-up greater than 18 months, the functional outcomes were graded good to excellent. CONCLUSION: The short-term oncologic and orthopedic results are encouraging and suggest that ECI provides a good alternative for reconstruction in limb conservative surgery in selected patients. This technique should only be used in a multidisciplinary setting, where careful follow-up is available to assess the long-term outcomes.     

In vivo knockdown of basal forebrain p75 neurotrophin receptor stimulates choline acetyltransferase activity in the mature hippocampus

This study seeks to determine whether knockdown of basal forebrain p75 neurotrophin receptor (p75^NTR) expression elicits increased hippocampal choline acetyltransferase (ChAT) activity in mature animals. Antisense (AS) oligonucleotides (oligos) targeting p75^NTR were infused into the medial septal area of mature rats continuously for 4 weeks. In all rats, the cannula outlet was placed equidistant between the left and the right sides of the vertical diagonal band of Broca. We tested phosphorothioate (PS), morpholino (Mo), and gapmer (mixed PS/RNA) oligos. Gapmer AS infusions of 7.5 and 22 μg/day decreased septal p75^NTR mRNA by 34% and 48%, respectively. The same infusions increased hippocampal ChAT activity by 41% and 55%. Increased hippocampal ChAT activity correlated strongly with septal p75^NTR downregulation in individual rats. Infusions of PS and Mo AS oligos did not downregulate p75^NTR mRNA or stimulate ChAT activity. These results demonstrate that p75^NTR can dynamically regulate hippocampal ChAT activity in the mature CNS. They also reveal the different efficacies of three diverse AS oligo chemistries when infused intracerebrally. Among the three types, gapmer oligos worked best. © 2016 Wiley Periodicals, Inc.     

Behavioral avoidance test for childhood obsessive-compulsive disorder: a home-based observation

Obsessive-compulsive disorder (OCD) is one of the most debilitating of the anxiety disorders. As our knowledge about this childhood condition continues to grow, there is a need for controlled treatment-outcome trials with precise assessments that are sensitive to treatment change, to guide the development of effective interventions. To evaluate the efficacy of a treatment protocol, it is necessary to have reliable and sensitive measures of OCD symptoms, including measures of obsessions, compulsions, and related levels of distress and avoidance. Whilst structured diagnostic interviews, semistructured clinical interviews, and self-report measures have been widely used in the assessment of childhood OCD, related levels of behavioral distress and avoidance have not been measured in treatment-outcome trials. This study investigated the sensitivity of a behavioral avoidance test (BAT), conducted in the home environment, in assessing treatment-outcome effects for children and adolescents with OCD following a 14-week cognitive-behavioral therapy (CBT) family intervention, in comparison to children in an 8-week "waitlist" control group. The results of the current study strongly support the sensitivity of a standardized BAT in assessing treatment-related changes in children and adolescents with OCD. Implications and future directions for research are discussed.     

Punished behavior: Increases in responding after d-amphetamine

Responding maintained in squirrel monkeys under a 10-min fixed-interval schedule of food presentation was suppressed by presenting a shock after every 30 th response (punishment). During alternate 10-min periods of the same experimental session, but in the presence of a different discriminative stimulus, responding either had no effect (extinction) or postponed delivery of an electric shock (avoidance). During sessions when the avoidance schedule was not in effect, d-amphetamine sulfate decreased punished responding. When the avoidance schedule was present during alternate 10-min periods, however, d-amphetamine (0.01–0.56 mg/kg, i.m.) markedly increased responding during punishment components. Increases in responding during avoidance components were also evident. The effects of d-amphetamine on punished responding depend on the context in which that responding occurs.     

The Effects of the Odstock Drop Foot Stimulator on Perceived Quality of Life for People With Stroke and Multiple Sclerosis

Introduction. Gait speed is often used as a proxy for gait quality. However, some users of FES devices for correction of dropped foot choose to continue to use the device despite no significant change in speed. The Psychosocial Impact of Assistive Devices Scale (PIADS) was used to evaluate the effects of the Odstock Dropped Foot Stimulator (ODFS) on perceived quality of life (QOL) for people with stroke and multiple sclerosis (MS) and was compared with change in walking speed. Method. A total of 21 people with stroke and 20 with MS completed the PIADS questionnaire after 18 weeks of using the ODFS. Walking speed was recorded more than 10 m with and without stimulation. Results. Both groups recorded positive median scores for all three sections of the PIADS questionnaire: Competence (1.25 stroke, 0.91 MS), Adaptability (1.25 stroke, 0.50 MS), and Self‐esteem (0.88 stroke, 0.75 MS). These were significantly greater for the stroke than the MS group for Competence, p= 0.04 and Adaptability, p= 0.006. There was no significant correlation between changes in PIADS and changes in walking speed. Conclusions. FES for correction of dropped foot has a beneficial effect on perceived QOL for people with stroke and MS but this is not correlated with an objective measures of gait.     

The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population

Background

Sexually transmitted infection with the human papillomavirus (hpv) is responsible for a significant burden of human cancers involving the cervix, anogenital tract, and oropharynx. Studies in the United States and Europe have demonstrated an alarming increase in the frequency of hpv-positive oropharyngeal cancer, but the same direct evidence does not exist in Canada.

Methods

Using the London Health Sciences Centre pathology database, we identified tonsillar cancers diagnosed between 1993 and 2011. Real-time polymerase chain reaction was then used on pre-treatment primary-site biopsy samples to test for dna from the high-risk hpv types 16 and 18. The study cohort was divided into three time periods: 1993–1999, 2000–2005, and 2006–2011.

Results

Of 160 tumour samples identified, 91 (57%) were positive for hpv 16. The total number of tonsillar cancers significantly increased from 1993–1999 to 2006–2011 (32 vs. 68), and the proportion of cases that were hpv-positive substantially increased (25% vs. 62%, p < 0.002). Those changes were associated with a marked improvement in 5-year overall survival (39% in 1993–1999 vs. 84% in 2006–2011, p < 0.001). When all factors were included in a multivariable model, only hpv status predicted treatment outcome.

Interpretation

The present study is the first to provide direct evidence that hpv-related oropharyngeal cancer is increasing in incidence in a Canadian population. Given the long lag time between hpv infection and clinically apparent malignancy, oropharyngeal cancer will be a significant clinical problem for the foreseeable future despite vaccination efforts.