Waterloo Vision and Mobility Study: Normal gait characteristics during dark and light adaptation in individuals with age-related maculopathy

The purpose of this study was to evaluate the gait responses of individuals with low vision compared to those of normal-visioned individuals when their vision is challenged by extreme levels of light. Twenty subjects with age-related maculopathy (ARM) and 20 subjects with normal vision first walked along a flat, unobstructed path immediately after the ambient light level was changed from low (5 lux) to high (2500 lux). The procedure was repeated after the light was reduced from the high to the low level. Muscle activity, temporal and kinematic variables, and ground reaction forces were used to detect gait characteristics because of ambient light level changes. Data suggested that ARM subjects walked slower and with more caution than normal subjects but that these differences were not related to ambient light level. Head angle, an estimate of gaze direction, was lower for ARM subjects during high light, but the gaze direction for both groups was low during low light. Among these ARM subjects, extreme levels of ambient light did not affect gait; subjects made adaptations that were reasonable to encourage safe ambulation, despite the direction of light change. Normal-visioned individuals in this study experienced more difficulty in low light than high light situations.     

Allograft reconstruction of the acetabulum during revision total hip arthroplasty. Clinical, radiographic, and scintigraphic assessment of the results

In twenty-one hips of twenty-one patients, the acetabulum was reconstructed using allografts during revision of a total hip arthroplasty. The patients' average age at the time of revision was 64.3 years (range, nineteen to eighty-six years). At an average follow-up of 3.5 years (range, two to five years), three patients had died of causes unrelated to the hip reconstruction, and one had been lost to follow-up. In the other seventeen, the average Harris hip rating was 89 points (range, seventy to 100 points) at follow-up. In one patient the allograft collapsed, so that revision was required. Two patients had asymptomatic progressive radiolucencies at the cement-bone interface of the reconstructed acetabulum, and another had a 1.5-millimeter-wide lucency at the interface of the donor and recipient bone but was asymptomatic, and there had been no change in the position of the cemented acetabular component since operation. The remaining grafts appeared to be incorporated securely, as determined by radiographic examination. Three-dimensional computerized tomographic radioisotopic bone scans showed uniform uptake, consistent with revascularization and new-bone formation, in all grafts. There was no radiographic evidence of focal avascularity and there were no infections. Femoral-head bone allografts appear to provide a useful technique for the reconstruction of a severely deficient acetabulum during revision total hip arthroplasty.     

Effects of nicotine on bacterial toxins associated with cot death

Toxins produced by staphylococci and enterobacteria isolated from the nasopharynx of cases of sudden infant death syndrome (SIDS) have a lethal effect when injected into chick embryos. If the toxins are progressively diluted the lethal effect disappears, but certain combinations of toxins show synergy so that if sublethal doses are mixed a highly lethal effect is produced. In this paper it is shown that nicotine at very low concentrations (less than that produced in man by 0.05 cigarettes) potentiates the lethal action of certain SIDS associated bacterial toxins and markedly potentiates the lethal action of synergistic combinations of bacterial toxins. These results could explain, at least in part, why parental smoking increases the risk of SIDS. They also provide further support for the common bacterial toxin hypothesis of cot death.     

Encapsidated adenovirus mini-chromosome-mediated delivery of genes to the retina: application to the rescue of photoreceptor degeneration

First (DeltaE1/E3) and second (DeltaE1+DeltaE2/E3/E4) generation adenovirus (Ad) vectors have been shown previously to be of limited use in the treatment of human genetic diseases due to the induction of a host cytotoxic T-cell mediated immune response against virally expressed genes. In addition, a limited cloning capacity of approximately 8 kb does not cater for the incorporation of large upstream sequences essential for regulated tissue-specific expression or inclusion of multiple gene-expression cassettes. In this study we have exploited our recently developed Ad-based vector, the encapsidated adenovirus mini-chromosome (EAM) from which all of the viral genes have been deleted. EAMs contain only the inverted terminal repeats required for replication and five cis -acting Ad encapsidation signals necessary for packaging. We have shown previously that EAMs can efficiently transduce a variety of cell types in vitro. In this study we demonstrate that EAMs can transduce and rescue cells from the neurosensory retina in vivo. EAM-mediated delivery of the beta subunit of cyclic GMP phosphodiesterase (PDE) cDNA to mice affected with retinal degeneration (rd) allows prolonged transgene expression and rescue of rod photoreceptor cells. RT-PCR analysis from the injected retina indicates that transgene products are present for at least 18 weeks post-injection. Both the alpha and beta subunits of PDE could be detected up to 90 days postnatal in EAM-injected rd retina by western analysis. A maximal PDE activity of 150 nm/min/mg was detected at 33 days postnatal. Examination of outer nuclear thickness showed significant differences up to 12 weeks post-injection. These results demonstrate an improved level of rescue over first-generation adenoviral vectors and suggest the possibility of successful EAM- mediated treatment of some retinal diseases in humans.      

Changes in symptom scores as a potential clinical endpoint for studies of cystic fibrosis pulmonary exacerbation treatment

Introduction: Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822.Methods: Median daily CRISS reduction (i.e., improvement) and covariates associated with CRISS reduction by Day 14 were assessed by logistic regression.Results: Among 173 subjects, median baseline CRISS was 49 [IQR 41, 56]; 93.6% had a CRISS reduction of ≥11 (minimal clinically important difference); median time to –11 reduction was 2 days [95% CI 2, 3]. The greatest median CRISS difference from baseline, on Day 17, was –26 [–29, –23]. Odds of –26 CRISS change by Day 14 were greater in subjects with higher baseline CRISS (P=.006) and younger ages (P=.041).Conclusions: CRISS response has good dynamic range and may be a useful efficacy endpoint for PEx interventional trials. The optimal use of CRISS change as an endpoint remains uncharacterized.