Selective brain dopamine depletion in developing rats: an experimental model of minimal brain dysfunction.

Administration of 6-hydroxydopamine to neonatal rats produces a rapid and profound depletion of brain dopamine. Total activity of treated animals is significantly greater than that of controls between 12 and 22 days of age, but then declines, an activity pattern similar to that seen in affected children. This suggests a functional deficiency of brain dopamine in the pathogenesis of minimal brain dysfunction.

Provision of acute and elective general surgical care at a tertiary facility in the era of subspecialisation.

BACKGROUND: The need for an acute care and general surgical unit (ACGSU) to provide care for patients previously managed on an ad hoc basis by subspecialist units was recognised by the provincial government of the Western Cape Province, South Africa, the management of Groote Schuur Hospital (GSH) and the Department of Surgery. OBJECTIVE: To describe the resulting ACGSU and its functioning. METHODS: Data available from administrative records, patient files and operating room forms were collected in spreadsheet form for the period July 2013 - November 2016 inclusive. RESULTS: The ACGSU comprised a medical care team of four consultants and four to five trainees. A total of 7 571 patients were seen during the study period, the majority (66.1%) referred from the GSH Emergency Centre. Skin and soft-tissue infections formed the major disease complex. A total of 3 144 operative records were available. The most common procedures were wound debridement and inguinal hernia repairs. Trainees acted as primary surgeon in most cases. Complications (Clavien-Dindo grades I - V) were noted in 25.0% of patients. CONCLUSIONS: The ACGSU provides patient management that would otherwise complicate care in the subspecialist surgical units. It serves as a training ground for registrars and stands as a model for other institutions. Further research into the effect on patient care is planned.

Methylphenidate in 6-hydroxydopamine-treated developing rat pups. Effects on activity and maze performance.

In order to better devine the relationship between brain catecholaminergic mechanisms and the clinical syndrome of minimal brain dysfunction, we have developed an experimental model that has many of the features of the disorder seen in children. This model is effected by the preferential depletion of brain dopamine in 5-day-old rat pups following the intracisternal administration of 6-hydroxydopamine, and in the present investigation, we have examined the effects of methylphenidate hydrochloride (0.25 to 2.0 mg/kg) on activity levels and cognitive performance in normal and 6-hydroxydopamine treated animals. Methylphenidate therapy resulted in a significant increase in activity levels of normal rat pups 12 and 19 days of age; in contrast, methylphenidate administered to 6-hydroxydopamine-treated animals did not increase activity at 12 days of age and significantly reduced activity at 19 and 26 days. Methylphenidate had no effect on T-maze performance in normals, but significantly improved performance in 6-hydroxydopamine-treated animals. Our results suggest that the "paradoxical" response to methylphenidate found in 6-hydroxydopamine-treated rat pups may be the result of central denervation supersensitivity.

The effect of 6-hydroxydopamine on habituation of activity in the developing rat pup.

The role of brain catecholaminergic mechanisms in habituation of activity was investigated in rat pups treated with 6-hydroxydopamine (6-OHDA). Intracisternal administration of this agent in the neonatal period resulted in a permanent and significant depletion of brain dopamine to 35.5% of controls while brain norepinephrine remained unchanged. Activity levels in normal developing rat pups increased rapidly between 15-22 days, then declined at maturity (26 days), while activity in 6-OHDA treated animals during this peak period of behavioral arousal increased to a significantly greater degree than that of their littermate controls. Habituation of activity, defined as the decrement of spontaneous activity, was calculated by regression over the first 30 min of observation. At both 5 and 8 days of age 6-OHDA and control rat pups exhibited low levels of activity whose decrease with time did not differ significantly and this pattern continued through 12 days of age. However, by 15 days of age activity in control animals declined by 19% each 10 min period compared to only a 10% decline found in 6-OHDA animals. At 19 days normal rat pups declined by 10% compared to a significantly reduced decrement of 3% found in treated animals, but these differences were no longer apparent by 22, 26, or 29 days of age. Our results are consistent with the notion that habituation of activity is a complex phenomenon mediated in part by catecholaminergic systems.

Ontogenesis of spontaneous activity and habituation of activity in the rat pup.

Individual components of activity and habituation of activity were determined throughout the 1st month of life in the rat pup. Total activity increased from 25% at 8 days of age to 68% at 22 days before declining to 49% at 26 days. Total slight activity (predominantly sniffing) increased to a maximum of 33% at 15 days whereas total very active behavior (predominantly ambulation) reached its maximum of 38% at 22 days. Habituation of activity expressed as the mean slope of decrement of activity over the 1st 30 min of the observation period was observed in rats as young as 8 days of age. By 12 days, habituation of total activity had increased significantly reflecting a 3-fold increase ihabituation of slight activity, an effect observed at 15 days as well. However, by 19 days the slope of activity decrement had declined to half of its 15-day value, indicating an impairment of habituation and reflecting the attenuation of very active behavior, predominantly ambulation. This decline in habituation continued through 22 days but by 26 days habituation of activity had increased again reaching a maximum for the 1st month of postnatal life. Our results suggest that the phenomenon of behavioral arousal observed in the developing rat pup 19 days of age reflects an inability of the organism to modulate his activity as effectively as the 15-day- or 26-day-old animal.