Lower cardiorespiratory fitness in children with Type 1 diabetes.

AIMS: The present study aimed to compare cardiorespiratory fitness levels in children with and without Type 1 diabetes. In addition, the relationship between cardiorespiratory fitness and a range of physical and clinical factors was investigated. METHODS: Eighty-eight children with Type 1 diabetes aged 5-14 years completed a submaximal step test of cardiorespiratory fitness. Sixty-two of these children were successfully matched to control subjects without diabetes based on age, sex and anthropometrics for comparison. In addition, the relationship between cardiorespiratory fitness and a range of physical and clinical variables was assessed in the children with diabetes. RESULTS: The heart rate response to exercise was higher in children with Type 1 diabetes, indicating reduced cardiorespiratory fitness levels compared with control subjects. Both gender and glycaemic control (HbA(1c) ) were significantly associated with cardiorespiratory fitness, with female sex and poorer glycaemic control associated with reduced fitness. CONCLUSIONS: Future research should investigate whether the reduced fitness in children with Type 1 diabetes is attributable to lower physical activity levels, or physiological changes resulting from the diabetes pathology itself.

What is the functional outcome for the upper limb after stroke?

The Motor Assessment Scale (MAS) and the Functional Independence Measure (FIM) are commonly used in Australian rehabilitation centres but there have been few systematic studies using them to measure recovery after stroke, especially with regard to upper limb function. The aims of this study were to provide a profile of upper limb recovery in a non-surgical stroke population using measures of impairment and disability. The records of 153 subjects were audited for upper limb MAS sub-scores, the FIM sub-score for upper body dressing, and the total FIM score at admission and discharge from rehabilitation. Significant improvement occurred for all outcome measures. There was no relationship between the MAS scores and the functional task of upper body dressing. The results emphasize the importance of using outcome measures that assess both impairment and disability, and indicate that substantial improvements in upper limb function frequently occur after stroke. Although the MAS has limitations, it is a valuable tool for measuring upper limb outcome after stroke because it provides a more accurate profile of true upper limb recovery than the FIM.

Amphotericin B colloidal dispersion combined with flucytosine with or without fluconazole for treatment of murine cryptococcal meningitis.

Studies with animals and in vitro studies have demonstrated that flucytosine plus amphotericin B or fluconazole has significantly improved mycologic activity against meningitis caused by Cryptococcus neoformans compared to the activity of amphotericin B or fluconazole used alone. However, few doses have been tested in combination. This study evaluated the antifungal efficacy of amphotericin B colloidal dispersion (ABCD) combined with flucytosine with and without fluconazole in a murine model of cryptococcal meningitis. The following dosages were tested: ABCD at 0 to 12.5 mg/kg of body weight given intravenously 3 days/week, flucytosine at 0 to 110 mg/kg/day, and fluconazole at 0 to 50 mg/kg/day. Meningitis was established in male BALB/c mice by intracerebral injection of C. neoformans. Treatment with flucytosine with or without fluconazole dissolved in the sole source of drinking water was started on day 2; animals were sacrificed at 16 days, and the numbers of fungal colonies in the brain were quantified. A survival rate of 100% was achieved with ABCD plus flucytosine without fluconazole; however, the addition of fluconazole was required to prevent weight loss (P < 0.00001) and to achieve the maximum antifungal effect (P < 0.00001). The only region of dose combinations for which the 99% confidence intervals were less than 100 CFU/g of brain was defined by ABCD at 5.0 to 7.5 mg/kg combined with flucytosine at 20 to 60 mg/kg/day and fluconazole at 30 to 40 mg/kg/day. The triple combination of ABCD plus flucytosine and fluconazole was necessary to achieve the greatest antifungal activity.

Effect of severity of meningitis on fungicidal activity of flucytosine combined with fluconazole in a murine model of cryptococcal meningitis.

We studied the effect of the severity of meningitis on the response to therapy with fluconazole and flucytosine in a murine model of cryptococcal meningitis. Meningitis was established by intracerebral injection of Cryptococcus neoformans. The severity of meningitis was varied by delaying the onset of treatment from 3 to 7 days. Animals were sacrificed after 14 days of treatment, and the numbers of C. neoformans per gram of brain tissue were quantified. The range of effective dose combinations of fluconazole and flucytosine became progressively reduced as the severity of meningitis increased. The magnitude of treatment effect, as measured by the numbers of CFU/gram of brain tissue, was also reduced with increasing severity of meningitis. In this model, as the severity of meningitis increases, higher doses of fluconazole are required to achieve equivalent levels of activity. The combination of fluconazole and flucytosine appears to have the most-potent antifungal effects. This is most readily observed in animals with more-severe meningitis.

Adaptive optimization and the harvest of biological populations.

Adaptive management of renewable biotic resources accounts explicitly for uncertainties in system responses to management and recognizes the importance of reducing uncertainties while pursuing other management goals. An adaptive approach to the harvest of wildlife populations that are subject to (1) uncontrollable environmental variation, (2) uncertainties about the appropriate characterization of resource dynamics, (3) limitations on the controllability of harvest rates, and (4) uncertainties as to population status, expressed as sampling variation in the monitoring of populations and habitats, is described. Adaptive management is framed in terms of maximizing long-term harvest value against a background of various kinds and degrees of uncertainty, with an emphasis on structural uncertainty. By an appropriate extension of the "system state," adaptive optimization can be defined in terms of Markov decision processes. Solution algorithms are described for systems that are subject to structural uncertainty and are either partially or completely observable. Adaptive optimization is illustrated with an example in waterfowl harvest management that incorporates uncertainty in the relationship between harvest rates and survivorship.

Sublingual apomorphine solution in Parkinson's disease.

OBJECTIVE: To compare the effects of single doses of oral levodopa, subcutaneous apomorphine and sublingual apomorphine. DESIGN: Single-blind placebo-controlled comparative study. SETTING: Subjects were admitted as day patients to the neurology ward. PATIENTS: Five patients with idiopathic Parkinson's disease and "end of dose deterioration" entered and completed the study. INTERVENTIONS: Patients were given domperidone (20 mg by mouth three times a day) to prevent nausea and apomorphine (1-3 mg by subcutaneous injection), apomorphine in glycerol (10-30 mg sublingually) or their usual levodopa regimen. MAIN OUTCOME MEASURES: Efficacy, time to onset of effect and duration of effect of oral levodopa, subcutaneous apomorphine and sublingual apomorphine. Tremor amplitude and timed pegboard and gait tasks were used as objective indices of clinical state. RESULTS: Maximal efficacy of the three treatments was comparable (P = 0.28-0.99). Mean latency to onset of effect of both formulations of apomorphine was less than that of levodopa (P = 0.022-0.048) but so was the duration of effect (P = 0.044-0.049). CONCLUSIONS: Sublingual apomorphine may be a convenient means of rapidly terminating "off" periods associated with long term levodopa therapy.