Natural history of retinal degeneration in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinoses.

Neuronal ceroid lipofuscinoses (NCL; Batten disease) are a group of inherited neurodegenerative diseases with a common set of symptoms including cognitive and motor decline and vision loss. Naturally occurring sheep models of CLN5 and CLN6 disease display the key clinical features of NCL, including a progressive loss of vision. We assessed retinal histology, astrogliosis, and lysosomal storage accumulation in CLN5 affected (CLN5-/-) and CLN6 affected (CLN6-/-) sheep eyes and age-matched controls at 3, 6, 12, and 18 months of age to determine the onset and progression of retinal pathology in NCL sheep. The retina of CLN5-/- sheep shows progressive atrophy of the outer retinal layers, widespread gliosis, and accumulation of lysosomal storage in retinal ganglion cells late in disease. In contrast, CLN6-/- retina shows significant atrophy of all retinal layers, progressive gliosis, and earlier accumulation of lysosomal storage. This study has highlighted the differential vulnerability of retinal layers and the time course of retinal atrophy in two distinct models of NCL disease. This data will be valuable in determining potential targets for ocular therapies and the optimal timing of these therapies for protection from retinal dysfunction and degeneration in NCL.

Having it all: historical energy intakes do not generate the anticipated trade-offs in fecundity.

An axiom of life-history theory, and fundamental to our understanding of ageing, is that animals must trade-off their allocation of resources since energy and nutrients are limited. Therefore, animals cannot "have it all"--combine high rates of fecundity with extended lifespans. The idea of life-history trade-offs was recently challenged by the discovery that ageing may be governed by a small subset of molecular processes independent of fitness. We tested the "trade-off" and "having it all" theories by examining the fecundities of C57BL/6J mice placed onto four different dietary treatments that generated caloric intakes from -21 to +8.6% of controls. We predicted body fat would be deposited in relation to caloric intake. Excessive body fat is known to cause co-morbidities that shorten lifespan, while caloric restriction enhances somatic protection and increases longevity. The trade-off model predicts that increased fat would be tolerated because reproductive gain offsets shortened longevity, while animals on a restricted intake would sacrifice reproduction for lifespan extension. The responses of body fat to treatments followed our expectations, however, there was a negative relationship between reproductive performance (fecundity, litter mass) and historical intake/body fat. Our dietary restricted animals had lower protein oxidative damage and appeared able to combine life-history traits in a manner contrary to traditional expectations by having increased fecundity with the potential to have extended lifespans.

Optimisation of acid fast smears for the direct detection of mycobacteria in clinical samples.

AIMS: Despite its long history, the acid fast smear remains unstandardised. Technical variations in both the preparation of clinical material and subsequent staining mean that smear sensitivity relative to culture may vary from 50% to over 80%. This study assessed the sensitivity of acid fast microscopy at each of five stages of sample preparation and by both commonly used staining methods. METHODS: Sputum samples thought for varying reasons to be highly likely to be culture positive were used to prepare a series of smears in which the effects of digestion (liquefaction), concentration (centrifugation), and decontamination (sodium hydroxide) could be assessed, together with a comparison of staining by the auramine/phenol and Ziehl-Neelsen techniques. RESULTS: The most effective method for the demonstration of acid fast organisms in sputum was found to be an auramine phenol stain applied to a liquefied, concentrated sample and examined before the decontamination process. CONCLUSIONS: The auramine phenol stain applied to a liquefied, concentrated sample and examined before the decontamination process is the most effective method for the demonstration of acid fast organisms in sputum.

Reciprocating gait prosthesis for the bilateral hip disarticulation amputee.

This paper describes the design, manufacture and use of a new prosthesis which produced reciprocating gait for a bilateral hip disarticulation amputee. A special mechanism used the hip extension moment during weight bearing to drive the contralateral limb through the swing phase. The user rapidly attained efficient and safe reciprocating gait, together with simple donning and doffing. The success of this project has major implications for hip disarticulation amputees in terms of profound improvements of their independence and self-esteem.

Prevention of laboratory animal allergy.

Laboratory animal allergy (LAA) is a significant occupational hazard for workers in a number of research settings, including the pharmaceutical industry. Prevention of allergy and asthma is important because the illness can affect health and career. In a major pharmaceutical company, in an effort to prevent LAA, a comprehensive program to reduce exposure to environmental allergens was developed. The program included education, engineering controls, administrative controls, use of personal protective equipment, and medical surveillance. A prospective survey of five years of data was completed to determine the effect of the program on the prevalence and incidence of LAA. After instituting this program, we found that the prevalence of LAA ranged from 12%-22% and that the incidence was reduced to zero during the last two years of observation. We concluded that LAA is preventable through the implementation of a comprehensive effort to reduce exposure to allergens.

Undergraduate dermatology education in Canada: a survey.

BACKGROUND: Two reviews done in the 1980's showed that many Canadian medical schools scheduled relatively little time for dermatological teaching. Many students did not have a real clinical exposure to dermatology. OBJECTIVE: The purpose of this study was to obtain new data to reevaluate the undergraduate training in dermatology in Canada. METHODS: A survey was sent to the coordinators of undergraduate dermatology of all 16 Canadian medical schools. RESULTS: The survey of medical schools demonstrates the current status of dermatology undergraduate teaching across Canada. Although many improvements have been made in the way dermatology is taught to medical students, many of the problems noticed in the 1980s remain unresolved. CONCLUSION: Because dermatological care in Canada is often rendered by nondermatologists, the dermatologists should emphasize the importance of undergraduate training in their specialty.

A multicentre, parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis.

Short-contact treatment with dithranol (anthralin) is a widely used treatment for chronic plaque psoriasis. Although effective, it causes staining and irritation, and is therefore inconvenient. Calcipotriol is a recently developed vitamin D analogue which is effective and easy to use. To evaluate the relative efficacy, safety and acceptability of these treatments a multicentre, open, randomized, parallel-group comparison was performed. Four hundred and seventy-eight patients with chronic plaque psoriasis were randomized to use one of the two treatments for 8 weeks. One group applied calcipotriol ointment (50 micrograms/g) twice daily. The other used a single application for 30 min each day of Dithrocream in the highest concentration tolerated. Severity of psoriasis was assessed by modified PASI score at baseline, and after 2, 4, and 8 weeks of treatment. A five-point scale was used by subjects and by investigators as an additional assessment of overall response, and a similar scale was used by subjects to grade acceptability. Total serum calcium was monitored at baseline and after 2 and 8 weeks on treatment. The mean PASI score fell from 9.1 to 4.7 after 8 weeks on dithranol (P < 0.001), and from 9.4 to 3.4 on calcipotriol (P < 0.001). The difference between the two treatments was significant in favour of calcipotriol at 2 weeks (P < 0.001), and remained so at subsequent assessments. At 8 weeks the difference between mean improvements in scores for the two groups was 1.6 (95% confidence interval 0.5-2.7). Efficacy grading by subjects and investigators, and acceptability grading by subjects, were all significantly better for calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cold stress and exercise on fat loss in females.

A Latin Square design has been used to test the responses of 24 relatively fit young women to 200 minute bouts of exercise performed over 5 day trials under each of three different ambient conditions: 15 degrees C (warm-warm; (WW)); -20 degrees C while inhaling, from a facemask, air heated to 18 degrees C (cold-warm; (CW)); and -20 degrees C (cold-cold; (CC)). In both of the cold environments, special clothing and boots were provided (insulation 0.47 degree C X watt-1 X m-2 and 0.62 degree C X watt-1 X m-2; (4 and 3 CLO units)). All three trials led to a small (0.6-0.7 degree C) rise of rectal temperature, but in the two cold environments mean body temperatures fell by over 1.0 degree C. A large increase of serum ketones occurred under all conditions, and the exercise respiratory quotient suggested some increase of fat utilization, WW (0.85) through CW (0.84) to CC (0.83). A fat loss of about 0.5 kg over the five days was confirmed by hydrostatic weighing and measurement of skinfold thicknesses. This was much less than the change previously observed in men, and moreover, it seemed to be independent of ambient conditions. Possible reasons why cold did not increase fat loss in these women include: a lower relative intensity of exercise; a greater stability of fat stores in women; avoidance of caffeine; a possible translocation of subcutaneous fat to deep fat depots; and a greater desire to "lose weight" irrespective of environmental conditions.

Characteristics of patients found not to have multiple sclerosis.

Of 400 consecutive patients referred to Dalhousie University's multiple sclerosis research unit 52 (13%) were found not to have multiple sclerosis. Forty-one (79%) of the patients were female and 11 (21%) were male. About half of the patients had raised the suspicion of multiple sclerosis, and about half had either a medical background or a close association with a patient with the disease. Although in many cases a diagnosis was made at the initial visit, in difficult cases the most effective diagnostic technique was repeated assessment of the patient over a long period. It is important to keep an open mind when assessing patients suspected of having multiple sclerosis and to apply the recognized criteria for diagnosis of the disease.