Unilateral frontal lobectomy can produce strategy application disorder.

Following a 5 cm left frontal lobectomy for the removal of a mixed astrocytoma-oligodendroglioma, a 51 year old right handed man showed a marked dissociation between his performance on standard neuropsychological tests and his everyday behaviour. In contrast to his intact neuropsychological test performance, he was impaired on a test of "strategy application" which requires goal articulation, plan specification, self-monitoring, and evaluation of outcomes, as well as the establishment of mental "markers" to trigger specific behaviour. Strategy application disorder can therefore be produced by a unilateral circumscribed frontal lobe lesions.     

Production of 5–15 µm Diameter Alginate-Polylysine Microcapsules by an Air-Atomization Technique

A novel method of preparing small-sized microcapsules using a Turbotak air-atomizer is reported. Alginate-polylysine microcapsules containing Bacillus Calmette Guérin vaccine have been prepared by an adaptation of the method of Lim (1) which allows the manufacture of small-sized microcapsules. A Turbotak is used to spray sodium alginate solution into calcium chloride solution to form temporary calcium alginate microgel capsules. These temporary microgel droplets are subsequently cross-linked with polylysine to form permanent membranes. Microcapules in the size range of 5–15 µm have been produced which can be compared to an average diameter of 300 µm obtained by the method reported by Lim. The microcapsule size is dependent on the conditions of operation of the Turbotak and the concentration of the sodium alginate solution. Particles within the size range 5–15 µm can be reproducibly manufactured using the conditions of operation reported here. Other size ranges below the minimum of 300 µm reported by Lim are also feasible using this technique.     

Pharmacoeconomic evaluation of treatment of penetrating abdominal trauma.

The hospital, pharmacy, and antibiotic costs for patients with penetrating abdominal trauma were compared with reimbursement received; these costs were also analyzed to assess the potential impact of a total prospective pricing system (PPS). During a four-year period, 46 patients admitted solely for penetrating abdominal trauma were retrospectively evaluated: their discharge summaries indicated that, for 9 patients, reimbursement was based on diagnosis-related groups (DRGs) under the PPS; 9 patients had private insurance; and 28 were classified as "self-paying/no insurance." All costs, corrected for inflation, were reported in 1989 dollars. Antibiotics represented 22.5%, 1.7%, and 0.5% of pharmacy, hospital, and DRG reimbursement, respectively; pharmacy costs were 8.5% of hospital costs and 2.3% of DRG reimbursement. For all 46 patients, a net loss of $295 per patient was incurred. Four patients accounted for 43% of the hospital costs. If the hospital had been reimbursed for all of these patients by prospective pricing and DRGs, it would have had a median profit of $9730 in 42 of 46 patients. Costs exceeded DRG reimbursement in the remaining four patients by a median of $8210. Antibiotic costs and pharmacy costs represent a small portion of hospital costs and DRG reimbursement for patients with penetrating abdominal trauma; thus, cost containment efforts in these patients should be directed at other ancillary services and length of stay.     

A rejoinder to Professor Bruening

Point and Counterpoint

A rejoinder to Professor Bruening     

Recoding, storage, rehearsal and grouping in verbal short-term memory: an fMRI study

Functional magnetic resonance imaging (fMRI) of healthy volunteers is used to localise the processes involved in verbal short-term memory (VSTM) for sequences of visual stimuli. Specifically, the brain areas underlying (i) recoding, (ii) storage, (iii) rehearsal and (iv) temporal grouping are investigated. Successive subtraction of images obtained from five tasks revealed a network of left-lateralised areas, including posterior temporal regions, supramarginal gyri, Broca's area and dorsolateral premotor cortex. The results are discussed in relation to neuropsychological distinctions between recoding and rehearsal, previous neuroimaging studies of storage and rehearsal, and, in particular, a recent connectionist model of VSTM that makes explicit assumptions about the temporal organisation of rehearsal. The functional modules of this model are tentatively mapped onto the brain in light of the imaging results. Our findings are consistent with the representation of verbal item information in left posterior temporal areas and short-term storage of phonological information in left supramarginal gyrus. They also suggest that left dorsolateral premotor cortex is involved in the maintenance of temporal order, possibly as the location of a timing signal used in the rhythmic organisation of rehearsal, whereas Broca's area supports the articulatory processes required for phonological recoding of visual stimuli.     

Modeling place fields in terms of the cortical inputs to the hippocampus

A model of place-cell firing is presented that makes quantitative predictions about specific place cells' spatial receptive fields following changes to the rat's environment. A place cell's firing rate is modeled as a function of the rat's location by the thresholded sum of the firing rates of a number of putative cortical inputs. These inputs are tuned to respond whenever an environmental boundary is at a particular distance and allocentric direction from the rat. The initial behavior of a place cell in any environment is simply determined by its set of inputs and its threshold; learning is not necessary. The model is shown to produce a good fit to the firing of individual place cells, and populations of place cells across environments of differing shape. The cells' behavior can be predicted for novel environments of arbitrary size and shape, or for manipulations such as introducing a barrier. The model can be extended to make behavioral predictions regarding spatial memory.     

Pancreatic islet xenograft tolerance after short-term costimulation blockade is associated with increased CD4+ T cell apoptosis but not immune deviation

BACKGROUND: Our purpose was to determine if short-term inhibition of the CD40/CD40L and CD28/B7 costimulatory pathways was capable of inducing specific unresponsiveness to pancreatic islet xenografts and to ascertain the mechanism of tolerance induction. METHODS: Diabetic B6AF1 mice were transplanted with Wistar or DA rat islets and were treated short term with CTLA4-Fc and anti-CD40L mAb (MR1). RESULTS: Coadministration of CTLA4-Fc with MR1, resulted in indefinite rat islet xenograft survival in mice. Tolerance was species but not strain specific as long-term surviving recipients rejected third party BALB/c islet allografts but accepted a second rat islet xenograft from the same or different donor strain. Tolerance induction was associated with a large leukocyte infiltrate that did not exhibit features of immune deviation as intragraft T cell-specific cytokine gene expression was globally reduced. In particular, interleukin-4 gene expression was markedly suppressed. There was a complete inhibition of anti-donor IgG, IgG1, and IgM antibody in the serum of CTLA4-Fc/MR1- treated animals. Tolerance induction was associated with increased CD4+ T cell apoptosis as there was an increased proportion of annexin-V staining and Fas expressing CD4+ T cells and a decrease in CD4+ T cell Bcl-2 expression in the grafts and draining lymph nodes of CTLA4-Fc/MR1-treated recipients. CONCLUSION: Combined costimulatory blockade was capable of producing tolerance to pancreatic islet xenografts. The induction of this tolerant state was associated with increased T cell apoptosis, whereas the maintenance phase of tolerance was associated with the accumulation of a large number of inactive lymphocytes within the graft.     

A new cranial access device for cerebral monitoring

We report the design and clinical application of a new cranial access device (triple bolt) designed to transmit intracranial pressure monitors, multiparameter sensors, microdialysis catheters and laser doppler probes into the cerebral parenchyma. The objective was to achieve insertion on the Neuro-Critical Care Unit, imaging compatibility, angled trajectories and versatility of monitor application. The bolt has been successfully applied to 100 patients with severe head injury and subarachnoid haemorrhage.