A nurse-led paediatric oncology fast-track clinic proves a successful ambulatory intervention for patients.

AIM: To assess the impact of a pilot nurse-led paediatric oncology fast-track clinic (OFTC) for complications and side effects following chemotherapy within a paediatric tertiary hospital. METHODS: Prospective clinical data from the first 100 patients seen in the OFTC were compared with retrospective data of oncology patient presentations to the emergency department (ED) (over a 1-year period, n = 196) who would have been eligible for review in the OFTC. Parent and patient satisfaction of clinical care were also assessed via surveys pre- and post-OFTC implementation. RESULTS: Analysis which achieved statistical difference was a reduction in the number of blood tubes taken in OFTC (average 1.9 for those discharged from clinic, 2.9 for those admitted from clinic) in comparison to those seen in the ED (average 3.2) (p = 0.0027). The average number of interventions per patient seen in the ED were 2.1 (standard deviation 1.64) compared with 1.7 (standard deviation 1.55) interventions per patient seen in the OFTC, and who were not admitted following review. This result approached statistical significance with p = 0.0963. Other results which did not meet statistical significance included a reduction in treatment times, hospital admissions and medical oncology reviews. CONCLUSION: Our pilot study implementing an OFTC for the triage and assessment of chemotherapy-related complications has proven successful from an operational and consumer perspective. The clinic improved care by ensuring expedited review, more streamlined interventions, and less overall hospital admissions. The improvements in efficiency were also mirrored by increased parent and patient satisfaction.

A mobile cage facilitates periodic social contact and exercise for singly caged adult Vervet monkeys.

A mobile exercise cage that expands the quantity and improves the quality of the space available to singly caged adult Vervet monkey males is described. It was easily fitted into an existing caging system and the addition of a resident consort female made it possible for the males to mate and have regular social contact.

Modification of membrane-bound proteins of the hippocampus and entorhinal cortex by change in behavior in rats.

Rats were trained in an instrumental task for 2 X 25 min during 1 day and 4 days and compared with active controls with respect to membrane-bound proteins solubilized by chloral hydrate and fractionated on polyacrylamide gels. Then 30-micrograms samples of the hippocampus and entorhinal cortex were labeled by 14C- and 3H-valine. The distribution of the stained electrophoretogram was recorded by microdensitometry. The results show that the 1-day training induced an increased synthesis of a membrane protein fraction of 50,000 mol wt already present in the brain membrane proteins of active controls. Training for 4 days resulted in an overall stimulation of the hippocampal membrane protein fractions, especially in the higher-molecular-weight range. The entorhinal cortex showed two stimulated membrane protein fractions, 50,000 and 120,000 mol wt. Together with previous studies, this study makes it probable that training to establish a new behavior induces a modulation of both soluble and membrane-bound protein patterns in the hippocampus and the entorhinal cortex with a time phase retardation for the latter.

The effect of S100 protein on the plasma membrane function of neurons.

The protein S100 markedly increases the net intake of GABA across the plasma membrane of Deiters' neurons which have GABA receptors on their surfaces. This membrane function of S100 was found by using a new microtechnique. Plasma membranes of such cells have been freshly prepared by freehand microsurgery and are tightly fixed over a 30-micrometers phi hole between two compartments of a microchamber containing 2.0 mM GABA in 7.5 microliters and 0.2 mM GABA in 75 microliters, respectively. The transport of GABA has been determined after incubation of the membrane for from 30 sec to 10 min at 29 degrees C. GABA is transported at a rate of 145 ng in 3 min over a 700-micrometers2 membrane area. S100 in its calcium form reacts with the membrane and increases GABA transport by 20% which is ATP dependent and inhibited by ouabain and ruthenium red. The kinetics of the transport furthermore prove that GABA transport across the plasma membrane is an active process.

The effect of antiserum to S 100 protein on behavior and amount of S 100 in brain cells.

Since antiserum raised against the S 100 protein has an impairing effect on acquisition in behavioral tests, when interacting with S 100 on hippocampal cells, the effect of S 100 antiserum was studied in rats on the S 100 content of the hippocampus and thalamus, as well as on behavior. The operant reversal of handedness test and a light discrimination test were used. S 100 antiserum, 2 X 30 mu l, was injected intraventricularly before and during the sessions of two different learning tests. The S 100 protein was determined by quantitative immunoelectrophoresis. In the antiserum-injected animals, the levels of S 100 protein was increased by up to 30%, the incorporation values of 3H-valine increased in proteins of high molecular weight. Further acquisition was inhibited compared to controls, in which antiserum absorbed with pure S 100 protein was injected intraventricularly. The stimulation of S 100 synthesis, probably by the glia, may have occurred by a negative feedback effect, as has been observed in thymocytes.

S100-glia regulation of GABA transport across the nerve cell membrane.

A technique has been devised to isolate and prepare fresh nerve cell plasma membranes in order to study the transport of biologically active substances across the membrane and in the two opposite directions. The membrane is placed tightly over a 30-micrometer diameter hole in a thin glass plate forming a partition between two compartments of a micro-chamber made from silicon rubber. The plasma membrane is usually placed with the outer surface facing the upper compartment. We have studied the transport of labeled GABA across the plasma membrane of Deiters' nerve cells and the effect of the brain-specific protein S-100 in its calcium form on this process. 100 nl samples were separated by thin layer chromatography and each sample analyzed by an instrument especially made for low level 3H- and 14C-measurements. The S-100, Ca2+ protein significantly increased the GABA transport across the nerve cell membrane by maximally 25% and against a gradient. The kinetics of the transport process, and inhibition by 2-4 diaminobutyric acid, furthermore supported the conclusion that the S-100, Ca2+-stimulated GABA transport was an active process. When a thin layer of the nerve cell's S-100-synthesizing glia was placed in contact with the plasma membrane - as in the vivo situation - the stimulation of GABA transport was abrogated. The S-100, Ca2+ protein, if absorbed on the nerve cell membrane, stimulates GABA transport across the membrane. This phenomenon seems to be regulated by the glia which cover all parts of the plasma membrane except the post-synaptic areas.

Protein pattern alterations in hippocampal and cortical cells as a function of training in rats.

The study reports changes in the protein pattern and incorporation of L-[U-14C]-leucine in brain cells of the hippocampus and sensorimotor cortex of rats. The following subcellular fractions were analyzed by SDS-acrylamide gel electrophoresis: plasma membranes, synaptosomal membranes and synaptic mitochondria. Recurring reversal training gave an increased synthesis of synaptosomal membrane proteins with mol. wt. 35,000-45,000 and 60,000 and 100,000 in trained animals compared to active controls. Lesser changes were observed in plasma membrane and synaptic mitochondria fractions. Of the brain areas studied, the hippocampal synaptosomal fraction showed an initial, temporary response, and the cortical cell fractions responded subsequently. Judged from the time sequence of the protein response, it seems that recurrent reversal training induces a change in synaptic protein towards higher molecular weights, suggesting that these changes reflect a modification of the distribution of synaptic protein.

Response of a brain protein fraction 24 hours after training in rats.

The aim of the study was to follow the amount and incorporation of 14C-valine into separate, soluble protein fractions of the hippocampus, thalamus, and visual cortex of rats from 0 to 72 hr after training. The behavioral test consisted of reversal of handedness with training twice daily for 25 min for 2 days, followed by a 5-day intermission without training, and a final session of 24 min. The animals were injected intraperitoneally with 14C-valine 30 min before sacrifice and taken 0, 24, 48, and 72 hr after last training. After 24 hr, and only at that time, double incorporation values and increased amounts were observed in a protein fraction, No. 6 from the front, in all three brain areas of the trained rats compared to active controls. At 48 hr this protein fraction was at control level.

Brain proteins in undernourished rats during learning.

The effect of protein calorie undernourishment was studied in the hippocampus, the visual and the sensory-motor cortex of rats, subjected to a reversal learning test, with respect to protein fractions containing the acid proteins S-100 and 14-3-2. These proteins are brain specific and are confined to the nervous system of vertebrates and invertebrates. The 14-3-2 protein is localized in the fractions 4 and 5 counted from the anodal front in an acrylamide electrophoretic separation. Incorporation of 1-14-C-leucine and 3-H-leucine was determined in single and double-labeling experiments. The rats learned to discriminate between dark and light in a reversal and in a final re-reversal test. Extinction rats served as a comparison to trained rats although we stress the comparison trained, undernourished versus trained, fully fed rats. Behaviorally, the undernourished rats showed lower acquisition expressed as number of correct responses per trial block, but a somewhat higher rate of acquisition compared to the fully fed rats. In the untrained rats (undernourished versus fully fed) the following was found: a decreased amount of S100 in the visual cortex; an increased amount of S100 in the sensory-motor cortex. Significant differences existed in the biochemical response between the two groups of rats in the learning test (trained, undernourished versus trained, fully fed rats): decreased relative specific activities of the hippocampal S100, 4 and 5 proteins, and the 4 protein of the visual cortex; but increased relative specific activities of the 4 and 5 proteins of the sensory-motor cortex. Evidence is presented that these protein changes are specific. The changed response of the undernourished rats is interpreted as an adaption of the central nervous system to the stress on the organism induced by the protein calorie deficiency.

Localization and response of the 14-3-2 brain protein.

The 14-3-2 acidic protein specific for nerve tissue has been localized to bands 4 and 5 counted from the anodal front band in a polyacrylamide-gel electrophoretic pattern. The material consisted of cut-out layers of pyramidal nerve cells of the CA3 hippocampal region of the rat. Extracted protein samples were subjected to immunoprecipitation, Coons' double-layer immunofluorescence, microcomplement fixation, and a localization experiment using microdensitometry on a 400 muphi gel electrophoresis pattern with and without extra added 14-3-2 protein. The protein fractions 4 and 5, now shown to contain 14-3-2 protein, have recently been found to incorporate increased precursors at training as compared to controls.

Protein changes in different brain areas as a function of intermittent training.

Incorporation of [(3)H]leucine into protein of eight different brain areas in rats was determined during 1 month of intermittent training for reversal of handedness. The incorporation values of all areas of the trained animals were lower than those of the controls. This finding was corroborated by autoradiography. After initial training the relative specific activities of the sensory-motor and entorhinal cortex and reticular formation were low compared to those of the hippocampus. With more training and time, these values became inversed.

S100 brain protein: correlation with behavior.

The brain-specific acidic protein, S100, in the pyramidal nerve cells of the hippocampus was investigated as a possible correlate to learning during transfer of handedness in rats. The amount of S100 increased during training. Intraventricular injection of antiserum against the S100 protein during the course of training prevented the rats from further increases in learned behavior but did not affect motor function in the animals. Antibodies against the S100 protein could be localized after injection by immunofluorescence, in hippocampal structures, penetrating presumably through slight ependymal lesions caused by the injection. By contrast, control animals subjected to the same training and injected with S100 antiserum that had been absorbed with S100 protein or with other antisera against gamma-globulins showed no decrease in their ability to learn. The conclusion is that the brain-specific protein, S100, is linked to the learning process, at least within the training used.

Brain-cell protein synthesis specifically related to learning.

The study takes up the problem whether synthesis of certain protein fractions in nerve cells of the hippocampus in rats during the transfer of handedness may be specific for this learning process. Electrophoretic separation of protein was carried out on polyacrylamide gels at the microscale. The investigation encompasses the brain-specific, acidic protein S100 and two protein fractions moving close to the S100 protein during electrophoresis. The protein synthesis was studied during one month of intermittent training of the animals. The temporal link between behavior and an increase in the synthesis of nerve-cell protein indicates that the protein response is specific for the processes occurring in the hippocampus during learning.