Cerebral blood flow, arteriovenous oxygen difference, and outcome in head injured patients.

Cerebral blood flow (CBF) and other physiological variables were measured repeatedly for up to 10 days after severe head injury in 102 patients, and CBF levels were related to outcome. Twenty five of the patients had a reduced CBF [mean (SD) 0.29 (0.05) ml/g/min]; 47 had a normal CBF, (0.41 (0.10) ml/g/min); and 30 had a raised CBF (0.62 (0.14) ml/g/min). Cerebral arteriovenous oxygen differences were inversely related to CBF and averaged 2.1 (0.7) mumol/ml in the group with reduced CBF, 1.9 (0.5) mumol/ml in the group with normal CBF, and 1.6 (0.4) mumol/ml in the group with raised CBF. Patients with a reduced CBF had a poorer outcome than patients with a normal or raised CBF. Mortality was highest in patients with a reduced CBF, and was 32% at three months after injury, whereas only 21% of the patients with a normal CBF and 20% of the patients with a raised CBF died. There were no differences in the type of injury, initial score on the Glasgow Coma Scale, mean intracranial pressure (ICP), highest ICP, or the amount of medical treatment required to keep the ICP less than 20 mm Hg in each group. Systemic factors did not significantly contribute to the differences in CBF among the three groups. A logistic regression model of the effect of CBF on neurological outcome was developed. When adjusted for variables which were found to be significant confounders, including age, initial Glasgow Coma Score, haemoglobin concentration, cerebral perfusion pressure and cerebral metabolic rate of oxygen, a reduced CBF remained significantly associated with an unfavourable neurological outcome.     

Assessment of HER-2/neu status in breast cancer. Automated Cellular Imaging System (ACIS)-assisted quantitation of immunohistochemical assay achieves high accuracy in comparison with fluorescence in situ hybridization assay as the standard

This retrospective study of formalin-fixed infiltrating breast cancer specimens compared manual immunohistochemical assay with a new image analyzer-assisted immunohistochemical quantitation method, using fluorescence in situ hybridization assay (FISH) as the standard. Following the manual immunohistochemical assay, 189 cases, including most manual immunohistochemically positive and some random negative cases, were analyzed by FISH assay for Her-2/neu gene amplification and by the Automated Cellular Imaging System (ACIS) for immunohistochemical staining. Using the FISH standard, the ACIS immunohistochemical assay attained a higher concordance rate and sensitivity than the manual immunohistochemical assay (91.0% and 88% vs 85.7% and 71%, respectively), with only a slight decrease in specificity (93% vs 96%, respectively). In particular, the ACIS immunohistochemical assay resulted in a higher correlation with the FISH assay in the manual immunohistochemical assay 2+ cases. The ACIS immunohistochemical assay achieved higher accuracy than the manual method according to receiver operating characteristic curve analysis. The ACIS method represents a substantial improvement over the manual method for objective evaluation of the HER-2/neu status.     

Inhibition of in vivo tumorigenicity and invasiveness of a human glioblastoma cell line transfected with antisense uPAR vectors

Our previous studies showed that glioblastomas express increased urokinase-type plasminogen activator receptors (uPARs) in comparison to low-grade gliomas (Yamamoto et al., Cancer Res., 54, 5016-5020, 1994). To explore whether downregulation of uPAR inhibits tumor formation and invasiveness, a human glioblastoma cell line was transfected with a cDNA construct corresponding to 300 bp of the human uPAR's 5¢ end in an antisense orientation, resulting in a reduced number of uPA receptors. Co-culture studies with tumor spheroids and fetal rat brain aggregates showed that antisense SNB19-AS1 cells expressing reduced uPAR failed to invade fetal rat brain aggregates. Intracerebral injection of SNB19-AS1 stable transfectants failed to form tumors and were negative for uPAR expression in nude mice. Thus uPAR appears in this model to be essential for tumorigenicity and invasion of glioblastomas in vivo.     

Identification and validation of genes involved in the pathogenesis of colorectal cancer using cDNA microarrays and RNA interference.

PURPOSE: The purpose of this study was to profile gene expression changes in colorectal tumors to identify new targets and strategies for the management of this disease. EXPERIMENTAL DESIGN: cDNA microarray analysis was used to detect differences in gene expression between normal tissue and colon tumors and polyps isolated from 20 patients. To identify genes that are important in regulating the growth properties of colorectal cancer, RNA interference (RNAi) was used to disrupt expression of several of the overexpressed genes in a colon tumor cell line, HCT116, which showed similar patterns of gene expression as many of the patient tumors. RESULTS: Expression changes of > or =2-fold in approximately one-third of the patients were consistently observed for 2632 of a total of 9592 genes (574 up-regulated genes and 2058 down-regulated genes). Subsequent analysis of 13 genes by quantitative real-time PCR confirmed the reliability of this analysis. RNAi-mediated disruption of the expression of one of these genes, survivin, a potent inhibitor of apoptosis, severely reduced tumor growth both in vitro and in an in vivo xenograft model. CONCLUSIONS: The combined use of microarray analysis and RNAi provides an excellent system to define the role of specific genes that are up-regulated in cancer lead to the increased in vitro and in vivo growth of colon tumors.     

Isolated Ruptured Inter‐Atrial Septal Cystic Echinococcosis during Pregnancy

Herein, we present a case of asymptomatic isolated cardiac cystic echinococcosis localized entirely to the inter‐atrial septum in a pregnant woman. The patient underwent successful surgery. Cardiac cystic echinococcosis is rarely seen in pregnancy. A high index of suspicion is necessary for the diagnosis of a cardiac cyst hydatid. The treatment of cardiac cyst hydatid is surgical and should not be delayed during pregnancy. Early surgery might prevent septic embolization and cardiac life‐threatening complications and save the lives of both mother and baby as in the present case.     

A cohort cost analysis of lumbar laminectomy—current trends in surgeon and hospital fees distribution

Background contextSpine-related health-care expenditures accounted for $86 billion dollars in 2005, a 65% increase from 1997. However, when adjusting for inflation, surgeons have seen decreased reimbursement rates over the last decade.PurposeTo assess contribution of surgeon fees to overall procedure cost, we reviewed the charges and reimbursements for a noninstrumented lumbar laminectomy and compared the amounts reimbursed to the hospital and to the surgeon at a major academic institution.Study design/settingRetrospective review of costs associated with lumbar laminectomies.Patient sampleSeventy-seven patients undergoing lumbar laminectomy for spinal stenosis throughout an 18-month period at a single academic medical center were included in this study.Outcome measuresCost and number of laminectomy levels.MethodsThe reimbursement schedule of six academic spine surgeons was collected over 18 months for performed noninstrumented lumbar laminectomy procedures. Bills and collections by the hospital and surgeon professional fees were comparatively analyzed and substratified by number of laminectomy levels and patient insurance status. Unpaired two-sample Student t test was used for analysis of significant differences.ResultsDuring an 18-month period, patients underwent a lumbar laminectomy involving on average three levels and stayed in the hospital on average 3.5 days. Complications were uncommon (13%). Average professional fee billing for the surgeon was $6,889±$2,882, and collection was $1,848±$1,433 (28% overall, 30% for private insurance, and 23% for Medicare/Medicaid insurance). Average hospital billing for the inpatient hospital stay minus professional fees from the surgeon was $14,766±$7,729, and average collection on such bills was $13,391±$7,256 (92% overall, 91% for private insurance, and 85% for Medicare/Medicaid insurance).ConclusionBased on this analysis, the proportion of overall costs allocated to professional fees for a noninstrumented lumbar laminectomy is small, whereas those allocated to hospital costs are far greater. These findings suggest that the current focus on decreasing physician reimbursement as the principal cost saving strategy will lead to minimal reimbursement for surgeons without a substantial drop in the overall cost of procedures performed.