Citations

The effect of hypercholesterolemia on the transverse wall properties of the upper descending thoracic aorta was studied in canines. Hypothyroid animals were fed a free diet supplemented with cholesterol, propylthiouracil, and saturated fat (lard) for 11 mo. The mechanical properties of the wall showed marked changes following experimental pathology. The failure stress, failure elongation, and energy to failure decreased following hypercholesterolemia. The tensile response was bilinear in both the pathological and control tissues. In the initial region, which is controlled by elastic fibers, the response was left unchanged by the experimental pathology. In the secondary region, which is controlled by stretching of the collagen fibers, the intercept with the strain axis and the slope were decreased by the pathology. This indicates that there are changes in the strength-bearing collagen and its interaction with the amorphous matrix. However, no significant parallel histological changes were observed in the structure of collagen and elastic fibers. Although this phenomenon precedes the development of atherosclerotic plaques which are charateristic of a diagnosed human disease, the aortic wall is already “hardened” because of its reduced compliance resulting from the shift in the onset of secondary (collagenous) response.

Since the electrogoniometric method has been justified for the measurement of lower extremity joint motion, a similar device is developed for the measurement of elbow joint and forearm rotations. In this design, the axis of forearm rotation coincides with the anatomical axis which eliminates the cross talk existing in the regular triaxial goniometer. Although the axis of abduction-adduction is still offset from the elbow joint, special linkage arrangement was used to obtain equivalent motion. Experimental method was used to validate the accuracy of the device and model simulation was performed to emphasize the importance of accurate placement of the instrument on test subjects. Application of the present apparatus to normal subjects was studied to illustrate the range of elbow motion required in performing normal activities of daily living. This device is currently used in the functional evaluation of patients with elbow and forearm problems.

Abstract Purpose: Various studies have shown the importance of the GAIP interacting protein, COOH-terminus (GIPC, also known as Synectin) as a central adaptor molecule in different signaling pathways and as an important mediator of receptor stability. GIPC/Synectin is associated with different growth-promoting receptors such as insulin-like growth factor receptor I (IGF-IR) and integrins. These interactions were mediated through its PDZ domain. GIPC/Synectin has been shown to be overexpressed in pancreatic and breast cancer. The goal of this study was to show the importance of GIPC/Synectin in pancreatic cancer growth and to evaluate a possible therapeutic strategy by using a GIPC-PDZ domain inhibitor. Furthermore, the effect of targeting GIPC on the IGF-I receptor as one of its associated receptors was tested. Experimental Design: The in vivo effects of GIPC/Synectin knockdown were studied after lentiviral transduction of luciferase-expressing pancreatic cancer cells with short hairpin RNA against GIPC/Synectin. Additionally, a GIPC-PDZ–targeting peptide was designed. This peptide was tested for its influence on pancreatic cancer growth in vitro and in vivo. Results: Knockdown of GIPC/Synectin led to a significant inhibition of pancreatic adenocarcinoma growth in an orthotopic mouse model. Additionally, a cell-permeable GIPC-PDZ inhibitor was able to block tumor growth significantly without showing toxicity in a mouse model. Targeting GIPC was accompanied by a significant reduction in IGF-IR expression in pancreatic cancer cells. Conclusions: Our findings show that targeting GIPC/Synectin and its PDZ domain inhibits pancreatic carcinoma growth and is a potential strategy for therapeutic intervention of pancreatic cancer.

Objective. A study supported by the EULAR and the ACR being conducted to establish classification criteria for polymyalgia rheumatica (PMR) will include ultrasound examination of the shoulders and hips. Ultrasound (US) depicts glenohumeral joint effusion, biceps tenosynovitis, subdeltoid bursitis, hip joint synovitis, and trochanteric bursitis in PMR. These findings may aid in distinguishing PMR from other diseases. The purpose of this study was to assess standards and US interreader agreement of participants in the PMR classification criteria study.Methods. Sixteen physicians in four groups examined shoulders and hips of 4 patients and 4 healthy adults with ultrasound. Overall agreement and interobserver agreement were calculated.Results. The overall agreement (OA) between groups was 87%. The OA for healthy shoulders was 88.8%, for healthy hips 100%, for shoulders with pathology 85.2%, and 74.3% for hips with pathology, respectively.Conclusion. There was a high degree of agreement found for the examination of healthy shoulders and pathologic hips. Agreement was moderate for pathologic shoulders and perfect for healthy hips. US of shoulder and hips performed by different examiners is a reliable and feasible tool for assessment of PMR related disease pathology and can be incorporated into a classification criteria study.

Diffuse axonal injury (DAI) with prolonged coma has been produced in the primate using an impulsive, rotational acceleration of the head without impact. This pathophysiological entity has been studied subsequently from a biomechanics perspective using physical models of the skull-brain structure. Subjected to identical loading conditions as the primate, these physical models permit one to measure the deformation within the surrogate brain tissue as a function of the forces applied to the head. An analytical model designed to approximate these experiments has been developed in order to facilitate an analysis of the parameters influencing brain deformation. These three models together are directed toward the development of injury tolerance criteria based upon the shear strain magnitude experienced by the deep white matter of the brain. The analytical model geometry consists of a rigid, right-circular cylindrical shell filled with a Kelvin-Voigt viscoelastic material. Allowing no slip on the boundary, the shell is subjected to a sudden, distributed, axisymmetric, rotational load. A Fourier series representation of the load allows unrestricted load-time histories. The exact solution for the relative angular displacement (V) and the infinitesimal shear strain (ε) at any radial location in the viscoelastic material with respect to the shell was determined. The strain response for brain tissue (μ = 345 Poise, G = 1.38 × 104 Pa) was examined at the non-dimensional radial location R = 0.3. The size (1.8<R0<6.8 cm) and constitutive properties of the brain, and the magnitude, duration (2<TD<100 msec) and waveform (sine, square, triangle) of the applied load were varied independently; each contributed to the response of the tissue. Strain increased linearly with increasing magnitude of the applied load and exponentially with increasing brain size (where the exponent n was frequency-dependent). Peak angular acceleration (Θ¨p) and peak angular velocity (ΔΘ˙p) were defined as appropriate load descriptors. As ΔΘ˙p increased, strain rose rapidly and was independent of Θ¨p, then levelled off and was highly sensitive to Θ¨p.

Background and Purpose— Transient ischemic attacks are a frequent diagnosis in the emergency department setting, yet expert opinion as to the proper follow-up and need for hospitalization differs widely. Recently, an effort has been made to risk-stratify patients presenting with transient ischemic attacks through scoring systems such as the ABCD and ABCD2 scales. The aim of our study was to independently validate these scores using a population-based cohort. Methods— Using the data from the Rochester Stroke and Transient Ischemic Attack Registry and resources of the Rochester Epidemiology Project, medical records of all residents of Rochester, Minn, with a diagnosis of incident transient ischemic attack from 1985 through 1994 were examined (N=284). Patients were scored on the ABCD and ABCD2 scales and new scores were created by adding hyperglycemia and a history of hypertension. The end points of stroke and death were collected previously and were verified through the Rochester Epidemiology Project data. Results— Although our study did find that scores >4 had a statistically significant predictive value for future stroke, a substantial proportion of strokes within 7 days (9 of 36 cases [25%]) occurred in patients with low or intermediate risk scores (≤4) on the ABCD2 scale. Including history of hypertension and hyperglycemia on presentation increased the sensitivity of the score to identify patients who had a stroke within 7 days. Conclusions— Reliance on the ABCD and ABCD2 scores misses some patients who will have a stroke within 7 days of a transient ischemic attack. Adding hyperglycemia and a history of hypertension to the predictive model could be useful, but the value of these additions need to be evaluated further.

Abstract Background: The repertoire of serologic tests for identifying a monoclonal gammopathy includes serum and urine protein electrophoresis (PEL), serum and urine immunofixation electrophoresis (IFE), and quantitative serum free light chain (FLC). Although there are several reports on the relative diagnostic contribution of these assays, none has looked at the tests singly and in combination for the various plasma cell proliferative disorders (PCPDs). Methods: Patients with a PCPD and all 5 assays performed within 30 days of diagnosis were included (n = 1877). The diagnoses were multiple myeloma (MM) (n = 467), smoldering multiple myeloma (SMM) (n = 191), monoclonal gammopathy of undetermined significance (MGUS) (n = 524), plasmacytoma (n = 29), extramedullary plasmacytoma (n = 10), Waldenström macroglobulinemia (WM) (n = 26), primary amyloidosis (AL) (n = 581), light chain deposition disease (LCDD) (n = 18), and POEMS syndrome (n = 31). Results: Of the 1877 patients, 26 were negative in all assays. Omitting urine from the panel lost an additional 23 patients (15 MGUS, 6 AL, 1 plasmacytoma, 1 LCDD), whereas the omission of FLC lost 30 patients (6 MM, 23 AL, and 1 LCDD). The omission of serum IFE as well as urine lost an additional 58 patients (44 MGUS, 7 POEMS, 5 AL, 1 SMM, and 1 plasmacytoma). Conclusions: The major impact of using a simplified screening panel of serum PEL plus FLC rather than PEL, IFE, and FLC is an 8% reduction in sensitivity for MGUS, 23% for POEMS (7 patients), 4% for plasmacytoma (1 patient), 1% for AL, and 0.5% for SMM. There is no diminution in sensitivity for detecting MM, macroglobulinemia, and LCDD.

Abstract Background: Previous comparisons of monoclonal protein quantification identified a bias between serum protein electrophoresis (SPEP) and immunonephelometry (NEPH). Methods: We reviewed data from 2845 patients in whom a single sample provided a γ fraction M-spike by SPEP, a heavy chain isotype by immunofixation electrophoresis (IFE), and an Ig quantification by NEPH. We examined the relationship between SPEP and NEPH. Selected sera with high monoclonal protein concentrations were diluted and reassessed. Results: For all isotypes, the relationship between SPEP and NEPH was best fitted with cubic curves. We determined the concentrations of each isotype that fitted a linear relationship. IgA had the best correspondence (slope 0.92, 95% CI 0.87–1.02), whereas IgM demonstrated a systematic bias of higher values by NEPH (slope 1.80, 95% CI 1.68–1.92). IgG demonstrated a nonlinear relationship between SPEP and NEPH, with a linear region &lt;19.2 g/L having a slope of 0.83 (95% CI 0.79–0.89) and a second linear region having a slope of 1.47 (95% CI 1.39–1.53) at higher concentrations. Dilutions of high-concentration IgG monoclonal proteins were linear by NEPH and nonlinear by SPEP. Conclusions: There are systematic differences in the quantification of monoclonal IgM and IgG by SPEP and NEPH. The bias in IgM is from NEPH overestimation. The nonlinearity of SPEP at high monoclonal IgG concentrations may obscure changes in plasma cell populations. Clinicians should be made aware of the biases and nonlinearity in these tests to make proper conclusions regarding treatment response.