Comparison of the Diagnostic Utility of 4D-DSA with Conventional 2D- and 3D-DSA in the Diagnosis of Cerebrovascular Abnormalities.

BACKGROUND AND PURPOSE: 4D-DSA is a time-resolved technique that allows viewing of a contrast bolus at any time and from any desired viewing angle. Our hypothesis was that the information content in a 4D-DSA reconstruction was essentially equivalent to that in a combination of 2D acquisitions and a 3D-DSA reconstruction. MATERIALS AND METHODS: Twenty-six consecutive patients who had both 2D- and 3D-DSA acquisitions were included in the study. The angiography report was used to obtain diagnoses and characteristics of abnormalities. Diagnoses included AVM/AVFs, aneurysms, stenosis, and healthy individuals. 4D-DSA reconstructions were independently reviewed by 3 experienced observers who had no part in the clinical care. Using an electronic evaluation form, these observers recorded their assessments based only on the 4D reconstructions. The clinical evaluations were then compared with the 4D evaluations for diagnosis and lesion characteristics. RESULTS: Results showed both interrater and interclass agreements (κ = 0.813 and 0.858). Comparing the 4D diagnosis with the clinical diagnosis for the 3 observers yielded κ values of 0.906, 0.912, and 0.906. The κ values for agreement among the 3 observers for the type of abnormality were 0.949, 0.845, and 0.895. There was complete agreement on the presence of an abnormality between the clinical and 4D-DSA in 23/26 cases. In 2 cases, there were conflicting opinions. CONCLUSIONS: In this study, the information content of 4D-DSA reconstructions was largely equivalent to that of the combined 2D/3D studies. The availability of 4D-DSA should reduce the requirement for 2D-DSA acquisitions.

Validity of height loss as a predictor for prevalent vertebral fractures, low bone mineral density, and vitamin D deficiency.

Many osteoporosis-related vertebral fractures are unappreciated but their detection is important as their presence increases future fracture risk. We found height loss is a useful tool in detecting patients with vertebral fractures, low bone mineral density, and vitamin D deficiency which may lead to improvements in patient care. INTRODUCTION: This study aimed to determine if/how height loss can be used to identify patients with vertebral fractures, low bone mineral density, and vitamin D deficiency. METHODS: A hospital database search in which four patient groups including those with a diagnosis of osteoporosis-related vertebral fracture, osteoporosis, osteopenia, or vitamin D deficiency and a control group were evaluated for chart-documented height loss over an average 3 1/2 to 4-year time period. Data was retrieved from 66,021 patients (25,792 men and 40,229 women). RESULTS: A height loss of 1, 2, 3, and 4 cm had a sensitivity of 42, 32, 19, and 14% in detecting vertebral fractures, respectively. Positive likelihood ratios for detecting vertebral fractures were 1.73, 2.35, and 2.89 at 2, 3, and 4 cm of height loss, respectively. Height loss had lower sensitivities and positive likelihood ratios for detecting low bone mineral density and vitamin D deficiency compared to vertebral fractures. Specificity of 1, 2, 3, and 4 cm of height loss was 70, 82, 92, and 95%, respectively. The odds ratios for a patient who loses 1 cm of height being in one of the four diagnostic groups compared to a patient who loses no height was higher for younger and male patients. CONCLUSIONS: This study demonstrated that prospective height loss is an effective tool to identify patients with vertebral fractures, low bone mineral density, and vitamin D deficiency although a lack of height loss does not rule out these diagnoses. If significant height loss is present, the high positive likelihood ratios support a further workup.

Clinical height measurements are unreliable: a call for improvement.

UNLABELLED: Height measurements are currently used to guide imaging decisions that assist in osteoporosis care, but their clinical reliability is largely unknown. We found both clinical height measurements and electronic health record height data to be unreliable. Improvement in height measurement is needed to improve osteoporosis care. INTRODUCTION: The aim of this study is to assess the accuracy and reliability of clinical height measurement in a university healthcare clinical setting. METHODS: Electronic health record (EHR) review, direct measurement of clinical stadiometer accuracy, and observation of staff height measurement technique at outpatient facilities of the University of Wisconsin Hospital and Clinics. We examined 32 clinical stadiometers for reliability and observed 34 clinic staff perform height measurements at 12 outpatient primary care and specialty clinics. An EHR search identified 4711 men and women age 43 to 89 with no known metabolic bone disease who had more than one height measurement over 3 months. The short study period and exclusion were selected to evaluate change in recorded height not due to pathologic processes. RESULTS: Mean EHR recorded height change (first to last measurement) was -0.02 cm (SD 1.88 cm). Eighteen percent of patients had height measurement differences noted in the EHR of ≥2 cm over 3 months. The technical error of measurement (TEM) was 1.77 cm with a relative TEM of 1.04 %. None of the staff observed performing height measurements followed all recommended height measurement guidelines. Fifty percent of clinic staff reported they on occasion enter patient reported height into the EHR rather than performing a measurement. When performing direct measurements on stadiometers, the mean difference from a gold standard length was 0.24 cm (SD 0.80). Nine percent of stadiometers examined had an error of >1.5 cm. CONCLUSIONS: Clinical height measurements and EHR recorded height results are unreliable. Improvement in this measure is needed as an adjunct to improve osteoporosis care.

Retrospective evaluation of canine and feline maxillomandibular trauma cases. A comparison of signalment with non-maxillomandibular traumatic injuries (2003-2012).

OBJECTIVES: To determine differences in signalment between maxillomandibular (MM) and non-maxillomandibular (non-MM) trauma patients to help predict the type of injury sustained. METHODS: A medical records database was searched from December 2003 to September 2012 to identify all MM trauma patients. A random sample of non-MM trauma patients was generated for comparison. Patient species, age, sex, weight, and injury aetiology were recorded for both populations. RESULTS: Sixty-seven MM trauma patients and 129 non-MM trauma patients were identified. Feline patients were almost twice as likely to be presented for MM trauma compared with non-MM trauma. The median weight of canine patients suffering MM injury was significantly less than that of non-MM patients (p = 0.025). A significant association existed between the causes of injuries associated with MM and non-MM trauma populations (p = 0.000023). The MM trauma patients were more likely to sustain injury as a result of an animal altercation (Bonferroni p = 0.001) while non-MM injuries were more likely to result from motor vehicle accidents (Bonferroni p = 0.001). Overall, animals that were less than one year of age with traumatic injuries were overrepresented (65/196) in comparison to the entire patient population. CLINICAL SIGNIFICANCE: The results of this study may help guide clinicians in the evaluation and screening of trauma patients that are presented as an emergency. Cats, small dogs and animals suffering from animal altercations should all be closely evaluated for MM injury.

Retrospective evaluation of canine and feline maxillomandibular trauma cases. Comparison of lunar cycle and seasonality with non-maxillomandibular traumatic injuries (2003-2012).

OBJECTIVES: To determine relationships between seasonality and lunar cycle and the frequency of maxillomandibular (MM) and non-maxillomandibular (non-MM) injury in canine and feline trauma patients. METHODS: A medical records database was searched to identify all MM trauma patients (n = 67) and a random sample of non-MM trauma patients (n = 129) according to search criteria. Season of injury, moon phase, and moon luminosity were calculated for the date of injury. RESULTS: Maxillomandibular injury occurred predominately in the spring and decreased through winter while non-MM injury occurred more frequently in the summer and fall. The difference in the frequency of MM and non-MM injuries during different seasons was not significant (p = 0.071). When comparing the amount of moon illuminated when injuries occurred during the quarters before or after the full moon, a difference (p = 0.007) was noted with a greater number of injuries occurring immediately following the full moon. CLINICAL SIGNIFICANCE: These results may guide clinicians to closely evaluate trauma patients that are presented on emergency during a particular season or lunar phase. Based on the season at the time of injury, close evaluation for MM versus non-MM trauma may be appropriate.

Peak CSF velocities in patients with symptomatic and asymptomatic Chiari I malformation.

BACKGROUND AND PURPOSE: PCMR is used to evaluate the Chiari I malformation. We compared quantitative PCMR in symptomatic and asymptomatic patients with Chiari I. MATERIALS AND METHODS: PCMR image data in an axial section near the foramen magnum in a consecutive series of patients with Chiari I malformations were evaluated. Patients were classified as symptomatic for a Chiari I if they had apnea spells and/or exertional headaches and as asymptomatic if they had symptoms not considered specific for a Chiari I malformation. The PCMR CSF flow study was obtained with the same protocol for all patients and with the neck in neutral, flexed, and extended positions. Images were inspected for CSF flow jets and synchronous bidirectional flow. Peak CSF flow velocities were calculated with commercial software. Differences between the 2 groups were tested with mixed-effects ANOVA and Wilcoxon rank sum or Fisher exact probability tests with significance set at the .05 level. RESULTS: Twenty-six patients with Chiari I were classified as symptomatic, and 24, as asymptomatic. Abnormal flow jets tended to occur more often in the symptomatic than in the asymptomatic patients (P = .054). Peak CSF velocities ranged from 2 to 20 cm/s in the symptomatic and the asymptomatic groups and did not differ significantly between the 2 groups or with neck position. CONCLUSIONS: Peak CSF flow velocities near the foramen magnum did not differentiate symptomatic and asymptomatic patients with Chiari I.

Direct detection of bacterial genomic DNA using gold nanoparticle probes.

The molecular probes and associated instrumentation necessary to perform genetic analyses are typically expensive, complex, and prone to error. While techniques such as real-time polymerase chain reaction (PCR) and gene expression analysis have provided a wealth of information previously unattainable, their utility in clinical diagnostics has yet to be realized due to the aforementioned limitations. Nanosphere Inc. has developed a gold nanoparticle-based platform for sequence specific DNA detection that is well-suited for clinical diagnostics due to its cost-effectiveness, simplicity, and accuracy. Thirteen nanometer gold nanoparticle probes, stabilized by a shell of oligonucleotides using proprietary attachment chemistries, enable highly sensitive and specific detection of bacterial genomic DNA sequences without synthetic amplification techniques on a glass array. After silver staining, light scattered by the nanoparticle probes is collected with robust, cost-effective instrumentation. It is the unique features of Nanosphere's detection methodology that provide the necessary steps forward to allow for genetic analyses to become part of routine clinical diagnostics.

Renal proximal tubular cell growth and differentiation are differentially modulated by renotropic growth factors and tyrosine kinase inhibitors.

BACKGROUND: The renotropic growth factors (GFs), hepatocyte GF (HGF), epidermal GF (EGF), and insulin-like GF-I (IGF-I) accelerate renal regeneration in animal models after toxic or ischemic injury. These GFs initiate their biological effects on renal tubular cells by interaction with specific transmembrane receptor tyrosine kinases. MATERIALS AND METHODS: In the proximal tubular cell line PT-1, the biological effects of HGF, EGF, and IGF-I and the growth-inhibitory effects of different tyrosine kinase inhibitors (TKIs) were investigated. Receptor binding and tyrosine kinase phosphorylation were determined by ligand binding studies and Western blot analysis. RESULTS: HGF, EGF, and IGF-I bound with nanomolar affinity to their specific cell membrane receptor tyrosine kinases. In contrast to EGF or IGF-I, HGF induced a variety of cell morphological changes, including cell scattering, formation of tubular structures, and expression of long microvilli on the apical cell membrane. HGF was a 10-fold more potent and more effective growth promoter than EGF or IGF-I. Among the TKIs tested, the mitogenic effect of HGF could be more specifically inhibited by emodin and tyrphostin, that of EGF by methyl-2,5-dihydroxycinnamate, lavendustin A, and genistein, and that of IGF-I by geldanamycin. CONCLUSIONS: In contrast to EGF and IGF-I, HGF stimulated both growth and differentiation of renal proximal tubular cells, demonstrating the amazing biological potency of this renotropic growth factor. Selective TKIs may be a promising approach to modulate diseases with abnormalities in protein kinase signalling pathways such as renal cell carcinoma.

Inhibitory effect of epidermal growth factor and hepatocyte growth factor on endothelin-1 release by rabbit proximal tubule cells.

Several studies have demonstrated an upregulation of endothelin-1 (ET-1) synthesis in acute and chronic renal failure. Epidermal growth factor (EGF) and hepatocyte growth factor (HGF) have been shown to stimulate renal tubular cell proliferation and to accelerate renal regeneration after drug-induced and ischemia-induced renal injury. This study aimed to investigate the effect of EGF and HGF on ET-1 release, and whether the effect of EGF and HGF is antagonized by the tyrosine kinase inhibitor lavendustin A. Rabbit proximal tubule cells were incubated for 48 h with EGF or HGF (0.1-10.0 nM), lavendustin A (0.1-10.0 microM) or co-incubated with EGF or HGF (1 nM) and lavendustin A. ET-1 concentrations in the culture medium were measured with a specific enzyme-linked immunosorbent assay (ELISA). EGF and HGF exerted a significant (p < 0.001) dose-dependent inhibitory effect on ET-1 release. Lavendustin A induced a dose-dependent stimulation of ET-1 release and antagonized the inhibitory effect of EGF and HGF on ET-1 release. The inhibition of EGF and HGF receptor tyrosine kinase activity by lavendustin A was confirmed by Western blotting. These data suggest that EGF and HGF reduce ET-1 release via EGF and HGF receptor tyrosine kinase activity. The inhibitory action of EGF and HGF on ET-1 release might be involved in mediating the protective effects of EGF and HGF in renal injury.

Loss & change: new directions in death education for adolescents.

The subject of this paper is Loss & change, a preventive health education school based program. The program has been developed, in conjunction with teachers, by a team of health workers from an Australian community health agency. This program is generalist in nature. It explores the losses adolescents experience within the context of healthy adolescent development. Based on a primary prevention model, it has a strong focus on life, and, as such, is a death education program which is different from those which focus on suicide prevention or bereavement support. The paper serves as an interim report on a program which is still developing, and which may provide some insight into a promising means of support for adolescent development.

Blebs and hematomas in the lips of CL/Fr and A/J mice.

Newborn-CL/Fr mice have +/- 20% frequency of cleft lip with or without cleft palate (CLP) depending on environment. However, examination of early fetal development from days 12 to 15 disclosed an increased number of hematomas or fluid-filled blebs in the regions of maxillary process fusion. The earliest stages do not appear to involve the blood supply directly but separate the epithelium from underlying mesenchyme by clear blebs. Similar defects were found in untreated A/J mice. These findings suggest that osmotic and hemodynamic abnormalities may be part of the mechanism of cleft lip formation in these related strains and that these defects may result from a biochemical defect of the connective tissue matrix in regions of process fusion.