Search PubMed⌕ Search

Biomedical subjects

W King

Publications and source records attributed to W King.

At least 91 records · Page 5Linked to original sources

Characterization of translational frame exception patients in Duchenne/Becker muscular dystrophy.

The clinical progression of Duchenne muscular dystrophy (DMD) patients with deletions can be predicted in 93% of cases by whether the deletion maintains or disrupts the translational reading frame (frameshift hypothesis). We have identified and studied a number of patients who have deletions that do not conform to the translational frame hypothesis. The most common exception to the frameshift hypothesis is the deletion of exons 3 to 7 which disrupts the translational reading frame. We identified a Becker muscular dystrophy (BMD) patient, an intermediate, and a DMD patient with this deletion. In all three cases, dystrophin was detected and localized to the membrane. One DMD patient with an inframe deletion of exons 4-18 produced no dystrophin. One patient with a mild intermediate phenotype and a deletion of exon 45, which shifts the reading frame, produced no dystrophin. Two patients with large inframe deletions had discordant phenotypes (exons 3-41, DMD; exons 13-48, BMD), but both produced dystrophin that localized to the sarcolemma. The DMD patient, 113, indicates that dystrophin with an intact carboxy terminus can be produced in Duchenne patients at levels equivalent to some Beckers. The dystrophin analysis from these patients, together with patients reported in the literature, indicate that more than one domain can localize dystrophin to the sarcolemma. Lastly, the data shows that although most patients show correlation of clinical severity to molecular data, there are rare patients which do not conform.

Adolescent↗

Prevention of bicycle-related injuries in childhood: role of the caregiver.

To assess perceptions of bicycle-related head injuries, helmet use, and safety practices, we had questionnaires distributed to caregivers of 2,500 children in the third through sixth grades; 1,006 (40.2%) completed surveys were returned. Eight hundred thirty-two caregivers (82.7%) indicated that they had a child cyclist in their household; approximately 65% responded that they believed head injury was likely if their child was involved in a bicycle mishap. A majority (approximately 70%) also said that a bicycle helmet may prevent head injury in between 25% and 75% of all occurrences. Yet 758 (91.1%) students did not own or have access to a bicycle helmet. Among the caregivers whose child did not have a bicycle helmet, 530 (69.9%) stated that they had never thought about purchasing one. Caregivers of both helmeted and nonhelmeted youngsters indicated concern for bicycle safety (100% versus 94%, respectively). Most caregivers (approximately 64%) stated that they would encourage their child to attend a bicycle safety camp. These findings suggest that caregivers perceive the dangers associated with bicycling but are not cognizant of available programs and methods that prevent the risk of serious injury to bicyclists.

Accident Prevention↗

A comparison of daily and alternate-day prednisone therapy in the treatment of Duchenne muscular dystrophy.

We previously reported the results of a randomized, double-blind 6-month trial of prednisone therapy in which 102 boys aged 5 to 15 years with Duchenne muscular dystrophy received daily doses of 1.5 and 0.75 mg/kg per day and were compared with those receiving placebo. The strength and function in both prednisone-treated groups improved equally and were significantly better than in the placebo group. To compare alternate-day and daily dosing of prednisone with respect to benefits and adverse side effects, the placebo group was started on alternate-day prednisone therapy, and the treatment group regimens were changed to equivalent doses of alternate-day prednisone without breaking the double-blind nature. At the end of 6 months, the group that was changed from daily to alternate-day therapy had declined in strength back to levels observed 12 months previously, at the start of daily therapy. The group in which alternate-day therapy was started showed a significant improvement in strength at 3 months, similar in magnitude to the response of boys treated with daily therapy. However, their strength declined significantly in the subsequent 3 months compared with boys who received daily therapy. The frequency of side effects was not significantly different for alternate-day therapy compared with daily therapy. We conclude that alternate-day prednisone therapy effectively increases strength but does not sustain the improvement to the same extent as daily therapy or mitigate side effects.

Adolescent↗

Fatal incidents involving pickup trucks in Alabama.

Death or injury resulting from crashes involving light trucks (ie, pickup trucks) is a significant problem. Data show that fatal crashes and occupant fatalities involving light trucks have steadily increased since 1983. This project describes vehicle crashes involving passengers riding in the beds of pickup trucks. Actual crashes were identified through the Fatal Accident Reporting System (FARS) of the National Highway Traffic Safety Administration. The 40 incidents studied involved 204 pickup truck passengers. Of these, 45 were killed, 107 sustained visible injuries or were carried from the scene, 6 had bruises and abrasions, and 2 had no visible injury but were briefly unconscious or had a documented complaint of pain. The risk of death among pickup truck passengers who were fully ejected from the vehicle was nearly six times that of passengers not fully ejected. Correspondingly, the risk of ejection from the truck was 26.7 times greater among occupants riding in the bed than occupants riding in the cab.

Accidents, Traffic↗

Long-term benefit from prednisone therapy in Duchenne muscular dystrophy.

Two successive, 6-month, randomized, double-blind, controlled trials of prednisone showed that 0.75 mg/kg/d was the optimal dose to improve strength in boys with Duchenne muscular dystrophy (DMD). We attempted to maintain 93 boys on that dose for an additional 2 years. During the 3 years of observation, the decline in average muscle strength scores of all boys taking prednisone was 0.072 units/yr, as compared with an expected decline of 0.341 units/yr from natural history controls. The occurrence of side effects in some boys prevented maintenance of the full dose, which may have lessened the response. At the time of last visit, dosages ranged from 0.15 mg/kg to 0.75 mg/kg. In addition to maintaining their strength, several of the boys actually improved their performance in lifting kilogram weights and in some timed function tests. Treatment of DMD with prednisone significantly slows the progression of weakness and loss of function for at least 3 years.

Adolescent↗

Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy.

We performed a randomized, double-blind, controlled six-month trial of prednisone in 103 boys with Duchenne's muscular dystrophy (age, 5 to 15 years). The patients were assigned to one of three regimens: prednisone, 0.75 mg per kilogram of body weight per day (n = 33); prednisone, 1.5 mg per kilogram per day (n = 34); or placebo (n = 36). The groups were initially comparable in all measures of muscle function. Both prednisone groups had significant improvement of similar degree in the summary scores of muscle strength and function. Improvement began as early as one month and peaked by three months. At six months the high-dose prednisone group, as compared with the placebo group, had improvement in the time needed to rise from a supine to a standing position (3.4 vs. 6.2 seconds), to walk 9 m (7.0 vs. 9.7 seconds), and to climb four stairs (4.0 vs. 7.1 seconds), in lifting a weight (2.1 vs. 1.2 kg), and in forced vital capacity (1.7 vs. 1.5 liters) (P less than 0.001 for all comparisons). There was an increase in urinary creatinine excretion (261 vs. 190 mg per 24 hours), which suggested an increase in total muscle mass. However, the prednisone-treated patients who had required long-leg braces (n = 5) or wheelchairs (n = 11) continued to require them. The most frequent side effects were weight gain, cushingoid appearance, and excessive hair growth. We conclude from this six-month study that prednisone improves the strength and function of patients with Duchenne's muscular dystrophy. However, further research is required to identify the mechanisms responsible for these improvements and to determine whether prolonged treatment with corticosteroids may be warranted despite their side effects.

Adolescent↗

Long-lasting alterations in behavior and brain neurochemistry following continuous low-level LSD administration.

Groups of rats were administered either 80 micrograms LSD-25 continuously over seven days using subcutaneous minipumps, or were given the same total amount of drug in seven daily injections, or were administered vehicle. When tested long after cessation of drug administration, persisting alterations in behavior and brain were found in the continuous LSD groups. In social open-field tests, this consisted of decreased social distance between animals; this effect increased upon repeated testing. In uptake of labeled ligands, this was reflected predominantly by decreased 3H-LSD binding in several limbic regions. LSD appears to have especially persisting neurotoxic effects when administered in a continuous, low-level fashion.

Animals↗

A new colorimetric nucleic acid hybridization assay for Listeria in foods.

Non-isotopic colorimetric detection has been applied in a rapid nucleic acid dipstick hybridization assay for detection of Listeria spp. in food and environmental samples. The assay takes approximately 2.5-3 h following a two day broth and plate enrichment. Hybridization occurs between fluorescein labeled detector probes, poly(deoxyadenosine)-tailed capture probes, and Listeria-specific regions of 16 S ribosomal RNA. These target:probe complexes are captured on poly(deoxythymidine) coated plastic dipsticks. Detection is based on binding of horseradish peroxidase conjugated anti-fluorescein antibody to the hybridization complex, and enzyme-mediated color development. The colorimetric endpoint is read on a photometer at 450 nm. In these initial studies, 306 inoculated dairy, meat and seafood samples, and 200 environmental samples were tested. When compared with total culture results the hybridization assay had unconfirmed positive and false-negative rates of approximately 1.4-2.9% and 0.8-4.7%, respectively.

Colorimetry↗

An evaluation of the Saskatchewan pit and fissure sealant program: a longitudinal followup.

The Saskatchewan Health Dental Plan (SHDP) is a publicly funded dental insurance program for children between the ages of five and 16 years residing in the province. In 1981, fissure sealants were added as a covered expense. Until September 1, 1987, sealants and other dental treatments covered under the SHDP were provided to schoolchildren by dental therapists in dental clinics established in elementary schools throughout the province. After September 1, 1987, the provision of dental services was transferred to private practitioners in the province. The objectives of this study were to (1) estimate the retention rates of sealants after one, two, and three years of placement; and (2) conduct a longitudinal followup of sealed and unsealed sound teeth to measure the effectiveness of sealants in reducing dental caries incidence. Relative to the first objective, a cohort of children was identified and comparisons were carried out for the periods of 1982-83, 1982-84, and 1982-85. For the last objective, a longitudinal evaluation of effectiveness was carried out only for children five to seven years of age in 1981. Saskatchewan children, who experienced higher caries prevalence than children in the United States, had the highest caries increments on occlusal surfaces of posterior teeth. About 79 percent of the sealants applied by dental therapists were retained three years after application. Sealed teeth experienced 46 percent less caries than unsealed teeth four years after the application of sealants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Squamous carcinoma of the gums.

We reviewed a 20-year experience with squamous carcinoma of the gums in 347 patients who received definitive therapy. More than three-quarters of the lesions involved the lower gum and all but 37 patients were previously untreated. The proportion of patients with localized tumors (N0) remained the same (64 percent). Surgery continued to be the treatment of choice in 97 percent of patients, but proportionately more patients had a more conservative procedure which preserved lower jaw continuity. The 5-year determinate survival rate was little changed (54 percent). Advanced clinical stage (stages III and IV), prior dental extraction, bone invasion, and involvement of surgical margins were predictive of a lower survival rate on univariate analysis. Clinical stage was the only significant predictor of survival on multivariate analysis. The impact of adjunctive radiotherapy could not be assessed.

Adult↗

Stress fractures of the tarsal navicular in long-distance runners.

The authors report on a study that attempted to (1) determine anatomic variations that predispose runners to tarsal navicular stress fractures; (2) study that loading responses of runners with stress fractures and of uninjured runners; (3) study the mechanical factors and biomechanics of the foot during running; (4) define a population at risk for developing stress fractures; and (5) propose an alteration in footwear that may reduce the force across the talonavicular joint.

Adolescent↗

Clinical investigation of Duchenne muscular dystrophy. A methodology for therapeutic trials based on natural history controls.

Between 1979 and 1987 we documented the natural history of Duchenne muscular dystrophy in 170 patients, aged from 3 to 23 years, by making serial measurements in over 5000 individual evaluations. This database makes it possible to design and conduct therapeutic trials using natural history controls. Such trials do not replace the need for randomized placebo-controlled trials of promising agents but they do require fewer patients, are cost-effective, and permit the use of high-risk therapy where toxicity monitoring may be important. Natural history-controlled trials, therefore, may serve as a screening method for new therapeutic agents. Drugs showing a significant benefit can then be evaluated in a randomized controlled trial.

Adolescent↗

Measuring disease activity: comparison of joint tenderness, swelling, and ultrasonography in rheumatoid arthritis.

In a prospective study of 6 patients with classic rheumatoid arthritis, we evaluated 3 measures of disease activity: comprehensive joint swelling and joint tenderness counts, and ultrasonography of joints. After baseline data were obtained on these 6 patients, therapy with fenbufen, a new nonsteroidal antiinflammatory drug, was begun. Followup examinations were performed at 4 weeks and 24 weeks after baseline. There were statistically significant differences between joint tenderness and joint swelling findings and between joint tenderness and joint ultrasonography findings (P less than 0.05 by kappa test statistic). In comparisons of joint swelling and ultrasonography, no difference was found (P greater than 0.05). When measures of changes over 6 months were compared, there was a high concordance between improvement in joint swelling and improvement in joint ultrasonography (P less than 0.01). Our results demonstrate that clinical assessment of joint swelling provides an accurate measure of synovial effusion, as confirmed by the more objective ultrasound measurements.

Arthritis, Rheumatoid↗

Chronic low-level lead exposure impairs embryonic to adult conversion of the neural cell adhesion molecule.

The neural cell adhesion molecule (N-CAM) is a complex of surface glycoproteins that are developmentally regulated and believed to be intimately involved in the orderly structuring of the CNS. Here the effect of chronic low-level lead exposure on their expression in the postnatally developing cerebellum is described. Rat pups were chronically exposed to lead via their dam's drinking water which contained either 200 or 400 mg PbCl2/L from time of birth. Pup postnatal blood lead levels ranged between 10 and 20 micrograms/dl until day 16 after which they became elevated to 40 micrograms/dl on day 20. During this period the developmental sialylation state of N-CAM, which is believed to regulate cell-cell interaction, fibre outgrowth, and synapse formation, was monitored by rocket immunoelectrophoresis. In control animals the expected desialylation of N-CAM was found to occur at times coincident with postnatal synaptogenesis. In contrast, desialylation in animals chronically exposed to lead was found to be significantly impaired when blood lead levels exceeded 20 micrograms/dl. This could not be attributed to lead-induced undernutrition or alterations in immunoprecipitate formation. These observations could account for the neurobehavioural deficits that are known to be induced at similar blood lead levels, and the potential contribution of impaired N-CAM desialylation to synaptic elaboration is discussed.

Aging↗