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.     

散发内淋巴囊瘤VHL基因位点微卫星标志杂合性丢失的研究

目的 探讨散发内淋巴囊瘤发病与VHL基因异常之间的关系。方法 采用组织微切割技术和多聚酶链式反应等方法对3例散发内淋巴囊瘤肿瘤细胞VHL基因位点染色体微卫星标志的杂合性丢失进行分析。结果 3例散发内淋巴囊瘤中有2例发生VHL基因位点微卫星标志的杂合性丢失,进一步的研究证实,该两例肿瘤细胞中分别存在着VHL基因第二外显子的异常。结论 VHL基因的异常导致其功能改变不但是VHL的致病原因,而且是散发性内淋巴囊瘤发病的重要的基因遗传学基础。     

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.     

Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Short-term wound complications after application of flaps for coverage of traumatic soft-tissue defects about the tibia. The Lower Extremity Assessment Project (LEAP) Study Group

BACKGROUND: The purpose of the present study was to compare the rate of short-term wound complications associated with rotational flaps and that associated with free flaps for coverage of traumatic soft-tissue defects about the tibia. METHODS: Of 601 patients prospectively enrolled in a multicenter study of high-energy trauma of the lower extremity, 190 patients (195 limbs) required flap coverage and had six months of follow-up. The injury data included the ASIF/OTA classification of the tibial fracture and the soft-tissue injury and the functional status of the neurovascular and muscular structures of the soft-tissue compartments at the time of soft-tissue coverage. The treatment data consisted of the type of flap, the timing of the flap coverage, and the type of fixation. The patient characteristics that were recorded included the age, gender, presence of comorbidities, and smoking status at the time of the injury. Short-term complications included wound infection, wound necrosis, and loss of the flap within the first six months after the injury. RESULTS: Eighty-eight limbs were treated with a rotational flap, and 107 limbs were treated with a free flap. Overall, complications occurred after fifty-three (27 percent) of the 195 flap procedures; forty-six (87 percent) of the fifty-three required operative treatment. The two treatment groups were similar with respect to age, gender, comorbidities, preinjury smoking status, ASIF/OTA classification of the fracture, and prevalence of vascular injury requiring repair (p>0.05). There were two important differences between the two groups. First, three of the four leg compartments--that is, the anterior, lateral, and deep posterior compartments--were more likely to be functionally compromised in the free-flap group than in the rotational flap group (p<0.05), suggesting that patients in the free-flap group had sustained more severe soft-tissue injuries. Second, the Injury Severity Score was significantly higher (p = 0.001) in the rotational flap group (mean, 14 points) than in the free-flap group (mean, 11 points), suggesting that patients in the former group had sustained more substantial total body trauma. Overall, there were no significant differences between the two groups with respect to the complication rates. However, among those with the most severe grade of underlying osseous injury (an ASIF/OTA type-C injury), 44 percent of the limbs that were treated with a rotational flap had a wound complication compared with 23 percent of the limbs that were treated with a free flap (p = 0.10). To control for any differences between the two groups with respect to the severity of the injury, the treatment methods, or the patient characteristics, multivariate regression modeling was performed. An interaction effect between the type of flap and the severity of the underlying osseous injury demonstrated significance (p<0.05) after controlling for other factors. Of the limbs that sustained an ASIF/OTA type-C osseous injury, those that were treated with a rotational flap were 4.3 times more likely to have a wound complication requiring operative intervention than were those treated with a free flap. No significant difference in the rate of complications was detected with respect to the type of flap used for the limbs that had lower-grade osseous injuries. CONCLUSIONS: We found that use of a free flap to treat limbs with a severe underlying osseous injury was significantly less likely to lead to a wound complication requiring operative intervention than was use of a rotational flap.