Precision of quantitative ultrasound: comparison of three commercial scanners

Quantitative ultrasound (QUS) measurements of bone have been shown to be independent predictors of osteoporotic fracture risk. Drawbacks of this technique have included the precision of the scanners, which is said to be poorer than in dual-energy X-ray absorptiometry (DXA), in part due to difficulty in repositioning of the foot in an os calcis system and difficulty in comparison across different technologies. A new type of QUS scanner has been introduced that produces an image of the area scanned and is believed to improve precision by aiding repositioning. In this study, we compare three scanners: a dry system (McCue CUBA Clinical); a nonimaging water-bath system (Lunar Achilles(+)); and an imaging water-bath system (Osteometer DTU-One). Short-term phantom precision was calculated by repeating measurements ten times in succession on the manufacturer-supplied phantom. Long-term phantom precision was calculated by examining the phantom measurements over a 6 month period. In vivo precision was calculated in 26 normal volunteers (19 women, 7 men) and 20 women with osteoporosis. Monitoring time intervals (MTIs) were also calculated using the manufacturer's normative database. The MTI is the period between scans required to show that a "true" change has occurred, and was between 0.5 year for stiffness (a derived index produced by the Lunar Achilles instrument) and >5 years for all other measurements. The imaging system did not seem to improve precision. Precision for the QUS phantom was similar to that of DXA with a coefficient of variation (CV) of around 1.5% for BUA and <1% for speed of sound (SOS). The precision was such that the technique may be considered for monitoring skeletal changes. However, the change of bone mass at the os calcis in response to treatment was slow, which made the time needed to wait before assessing change, on the whole, longer than that for DXA. An exception may be the Lunar Achilles "stiffness" parameter, but this can only be determined in a longitudinal, comparative treatment study.     

Inhibition of β-Catenin Translocation in Rodent Colorectal Tumors: A Novel Explanation for the Protective Effect of Nonsteroidal Antiinflammatory Drugs in Colorectal Cancer

In a rodent colorectal cancer model, nonsteroidal antiinflammatory drugs reduce tumor mass by increasing the rate of tumor cell apoptosis and decreasing proliferation. We have examined -catenin as a potential target for these agents in colorectal cancer. Carcinogen-treated rats were treated for 23 weeks with a range of nonsteroidal antiinflammatory drugs. Control animals received vehicle alone. Intracellular -catenin was examined using immunohistochemistry. In tumors from untreated animals, staining was seen in the cytoplasm and nucleus (median 24% of nucleii). The frequency of nuclear -catenin staining correlated directly with the volume of tumor and inversely with the rate of apoptosis. In tumors from treatment groups, the cytoplasmic staining for -catenin was unchanged; however, nuclear staining was absent except in the celecoxib group, where it was reduced to a median of 14%. Colorectal tumors from animals treated with NSAIDs show reduced levels of nuclear -catenin immunoreactivity.     

Headache types and panic disorder: directionality and specificity

OBJECTIVE: To examine the relationship of migraine and other severe headaches with panic disorder. METHODS: Representative samples of persons with migraine, non-migrainous severe headaches, and controls with no history of severe headaches, identified by a telephone survey, were interviewed in person, using a standardized psychiatric interview. Cox proportional hazards models with time-dependent covariates were used to examine the relationship of headaches with first-onset panic disorder and vice versa. RESULTS: Lifetime prevalence of panic disorder was significantly higher in persons with migraine and in persons with other severe headaches, compared with controls. Migraine and other severe headaches were associated with an increased risk for first onset of panic disorder (hazards ratios = 3.55 and 5.75). Panic disorder was associated with an increased risk for first onset of migraine and for first onset of other severe headaches, although the influences in this direction were lower (hazards ratios = 2.10 and 1.85). CONCLUSIONS: Comorbidity of panic disorder is not specific to migraine and applies also to other severe headaches. The influence is primarily from headaches to panic disorders, with a weaker influence in the reverse direction. The bidirectional associations, despite the difference in the strength of the associations, suggest that shared environmental or genetic factors might be involved in the comorbidity of panic disorder with migraine and other severe headaches.     

Left posterior BA37 is involved in object recognition: a TMS study

Functional imaging studies have proposed a role for left BA37 in phonological retrieval, semantic processing, face processing and object recognition. The present study targeted the posterior aspect of BA37 to see whether a deficit, specific to one of the above types of processing could be induced. Four conditions were investigated: word and nonword reading, colour naming and picture naming. Repetitive transcranial magnetic stimulation (rTMS) was delivered over posterior BA37 of the left and right hemispheres (lBA37 and rBA37, respectively) and over the vertex. Subjects were significantly slower to name pictures when TMS was given over lBA37 compared to vertex or rBA37. rTMS over lBA37 had no significant effect on word reading, nonword reading or colour naming. The picture naming deficit is suggested to result from a disruption to object recognition processes. This study corroborates the finding from a recent imaging study, that the most posterior part of left hemispheric BA37 has a necessary role in object recognition.     

Predictors of acquiring a nosocomial bloodstream infection on extracorporeal membrane oxygenation

PURPOSE: The aim of this study was to identify independent predictors of acquiring a nosocomial bloodstream infection (BSI) during extracorporeal membrane oxygenation (ECMO). METHODS: This retrospective cohort consisted of 202 neonates treated with ECMO from 1989 to 1998 at the author' institution. Data collected included patient demographics, primary and secondary diagnoses, white blood cell counts, antibiotic usage, presence of central lines, operative procedures, and outcome. Surveillance blood cultures were drawn daily from the circuit using sterile technique to identify acquired pathogens. Statistical analyses included logistic regression, Cox proportional regression analysis, and discriminate analysis. RESULTS: There were 1,245 blood cultures drawn on 202 patients (6.2 cultures per patient), and a nosocomial BSI was identified in 7 patients (3.4%) during this 10-year span. These were infections that were neither present nor incubating on admission. Pre-ECMO diagnoses of patients who had a nosocomial BSI while on bypass included group B beta-hemolytic streptococcal sepsis (n = 2), herpes simplex viral sepsis (n = 1), congenital diaphragmatic hernia (n = 2), persistent pulmonary hypertension (n = 1), and congenital heart disease (n = 1). The median time on ECMO before obtaining a positive culture was 390 hours. The infectious agents responsible for these BSIs included Staphylococcus epidermidis (n = 5), Staphylococcus aureus (n = 1), and Escherichia coli (n = 1). The major factor associated with acquiring a nosocomial BSI on ECMO was the duration of bypass (391 v 141 hours, P =.002). Additionally, patients in the BSI group were more likely to have had an arterial catheter in place (16 v 7 days, P =.009) and to have received more screening blood cultures (16 v 6 cultures, P < 001). White blood cell counts, absolute neutrophil counts, and immature/total (I/T) ratios were not useful in predicting a nosocomial BSI. Of the 31 patients who required ECMO for more than 10 days, 7 (23%) had a positive blood culture, and 5 of these 7 infants (71%) died (P =.03). CONCLUSIONS: The only predictor of acquiring a nosocomial BSI on ECMO was the duration of support for greater than 10 days. Because classical predictors of infection are unreliable while the patient is on ECMO, the authors suggest that obtaining daily surveillance blood cultures beginning on the tenth day should be performed with prolonged ECMO courses. The authors confirmed previous reports of the association between a prolonged ECMO course and a high mortality rate. However, the authors speculate that, in actuality, the primary diagnosis leads to the prolonged course of support and is the major factor in the infant' demise.     

Pediatric trauma registries: the foundation of quality care

BACKGROUND/PURPOSE: Traumatic injuries cause substantial morbidity and mortality in children. Trauma registries are essential to assess and improve standards of trauma care. An interprovincial study of pediatric trauma between 6 centers across Canada who use identical software components was completed. METHODS: Data were collected from April 1, 1995 to December 31, 1998 for children aged 1 day to 17 years with an injury severity score of > or = 12. Cause of injury, injury time and day, gender, age, injury scores, length of hospital stay, and outcomes were compared. RESULTS: A total of 1,276 patients were included. Mean age was 10.3 +/- 5.6 years. Motor vehicle collisions were the most common mechanism of injury (56%). Boys were more often injured (66%; P < .05). Injuries occurred mainly between 1600 and 2400 hours (P < .0001). Mean hospital stay was 11.5 +/- 16.6 days. The longest stays in the hospital were among those who had an abdominal abbreviated injury score (AIS) of 1 (P < or = .03). Patients with similar injury severities remained twice as long in Winnipeg Children's Hospital (hospital 5), hospital 2, and hospital 6 as compared with patients in hospital 3 (P < .05). Differences existed in discharge placement between hospitals (P < .0001). CONCLUSIONS: This study was the first to compare pediatric patients in multiple Canadian centers using identical trauma registries. Variations in length of stay and discharge placements between hospitals were identified. Further analysis of data in the registries may clarify these differences and serve as a foundation for hospitals to improve the quality of patient care.     

Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: in vitro and in vivo analysis

BACKGROUND: It has previously been demonstrated that 17-allylamino geldanamycin (17-AAG) enhances paclitaxel-mediated cytotoxicity and downregulates vascular endothelial factor expression in non-small cell lung cancer. This project was designed to evaluate the tumoricidal and antiangiogeneic effects of 17-AAG and paclitaxel in H358 non-small cell lung cancer cells grown as xenografts in nude mice. METHODS: In vitro cytotoxic drug combination effects were evaluated by (4, 5-dimethylthiazo-2-yl)-2, 5-diphenyl tetrazolium bromide-based proliferation assays. The combinations of 17-AAG and paclitaxel were administered intraperitoneally in nude mice bearing H358 tumor xenografts. Tumor volumes were measured weekly. Tumor expression of erbB2, vascular endothelial cell growth factor, von Willebrand factor (tumor microvasculature), and activated caspase 3 (apoptosis) were determined by immunohistochemistry. RESULTS: Five- to 22-fold enhancement of paclitaxel cytotoxicity was achieved by paclitaxel + 17-AAG combination that was paralleled with marked induction of apoptosis. This combination treatment profoundly suppressed tumor growth and significantly prolonged survival of mice bearing H358 xenografts. Immunohistochemical staining of tumor tissues indicated profound reduction of vascular endothelial cell growth factor expression associated with reduction of microvasculature in tumors treated with 17-AAG. Apoptotic cells were more abundant in tumors treated with 17-AAG + paclitaxel than in those treated with 17-AAG or paclitaxel alone. CONCLUSIONS: Concurrent exposure of H358 cells to 17-AAG and paclitaxel resulted in supraadditive growth inhibition effects in vitro and in vivo. Analysis of molecular markers of tumor tissues indicated that therapeutic drug levels could be achieved with this chemotherapy regimen leading to significant biological responses. Moreover, 17-AAG-mediated suppression of vascular endothelial cell growth factor production by tumor cells may contribute to the antitumor effects of this drug combination in vivo.