Measurement of kinetic parameters in skeletal muscle by magnetic resonance imaging with an intravascular agent.

The purpose of this work was to investigate the use of an intravascular contrast agent to determine perfusion kinetics in skeletal muscle. A two-compartment kinetic model was used to represent the flux of contrast agent between the intravascular space and extravascular extracellular space (EES). The relationship between the image signal-to-noise ratio (SNR) and errors in estimating permeability surface area product (Ktrans), interstitial volume (ve), and plasma volume (vp) for linear and nonlinear curve-fitting methods was estimated from Monte Carlo simulations. Similar results were obtained for both methods. For an image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%, respectively. In vivo experiments were conducted in rabbits to examine physiological differences between these parameters in the soleus (SOL) and tibialis anterior (TA) muscles in the hind limb. Values for Ktrans were significantly higher in the SOL (3.2+/-0.9 vs. 2.0+/-0.5x10(-3) min-1), as were values for vp (3.4+/-0.8 vs. 2.1+/-0.7%). Differences in ve for the two muscles (8.7+/-2.2 vs. 8.5+/-1.6%) were not found to be significant. These results demonstrate that relevant physiological metrics can be calculated in skeletal muscle using MRI with an intravascular contrast agent.     

Estimation of the DNA sequence discriminatory ability of hairpin-linked lexitropsins

Three- and four-ring polyamides containing N-methylimidazole and N-methylpyrrole, and their hairpin-linked derivatives, bind side-by-side in the minor groove of DNA in a sequence-specific manner. The sequences recognized by side-by-side molecules are dependent on the pairings of the polyamide rings to the bases. In this study we report a mathematical model for estimating the free energies of binding for γ-aminobutyric acid-linked polyamides to 5- and 6-bp DNA sequences. The model parameters are calibrated by a least-squares fit to 35 experimental binding constants. The model performs well in cross-validation experiments and the parameters are consistent with previously proposed empirical rules of polyamide–DNA binding. We apply the model to the design of targeted polyamides, evaluating the ability of the proposed polyamides to bind to a DNA sequence of interest while minimizing binding to the remaining DNA sequences.     

Constraints on Social Activities of Care-Givers: A Sociological Perspective

Newer policies of community care for those with disabilities have resulted in the home becoming the usual site of care. Policy makers must now give attention to the needs of those at home giving this care. This article explores the constraints on sociability opportunities of 73 mothers who were caring for children with disabilities. These opportunities are often built into leisure pursuits for women without caring responsibilities. However, choice of out-of-house leisure activity was circumscribed for the mothers in this study and their reported leisure activities revolved around home and neighbourhood. Even these sites offered limited scope for sociability because of the way in which caring affected domestic space and because of the characteristics of the modern Australian suburb. It is argued in this paper that personal time and personal domestic space are needed by care-givers so their sociability needs can be fulfilled. An understanding of the constraints imposed by use of the home as a place of care may make possible the planning of a rearrangement of domestic space to increase sociability opportunities for carers.     

BookReviews

Annals of Vascular Surgery -     

Percent spinal canal compromise on MRI utilized for predicting the need for surgical treatment in single-level lumbar intervertebral disc herniation

BACKGROUND CONTEXT: There is limited information describing the correlation between the initial quantitative measurements on magnetic resonance imaging (MRI) scans of disc herniation area, canal cross-section areas, percent canal compromise, and disc herniation location to the need for surgery. PURPOSE: Our aim is to determine if the size of disc herniation area, canal cross-section area, percent canal compromise, and disc herniation location taken from MRI images of patients with symptomatic single-level lumbar herniated intervertebral discs upon initial presentation to a spine surgeon, were predictive of the need for surgical treatment. STUDY DESIGN/SETTING: This is a retrospective case matched study of patient MRI images in the senior author's private practice. PATIENT SAMPLE: From a pool of 332 patients with sciatica caused by lumbar intervertebral disc herniations at our institution, 65 patients had surgery, of which MRI images were available and analyzed on 44 patients. Forty-four additional patients were randomly selected from the remaining 267 original group as nonoperative controls. METHODS: The axial MRI image showing the largest canal compromise by the herniated disc was selected for measurements. Using T1- and T2-weighted images, the areas of interest were digitally scanned at high resolution. The canal area and disc herniation area measurement were calculated from the total number of pixels per cross-sectional area, multiplied by a scan correction factor, mm(2) /pixel. Disc herniation locations were classified into either central or paracentral. The percent canal compromise was obtained by disc herniation area divided by canal cross-section area and multiplied by 100. RESULTS: The surgical group's overall mean herniated disc area was 219.6 square millimeter (mm(2)), 179.8 at L4-5, and 267.4 at L5-S1. The nonoperative group's overall mean herniated disc area was 178.4 mm(2), 135.1 at L2-3, 160.3 at L4-5, and 207.4 at L5-S1. The surgical group's overall mean canal cross-sectional area was 471.8 mm(2), 418.6 at L4-5, and 535.6 at L5-S1. The nonoperative group's overall mean canal cross-sectional area was 541.3 mm(2), 518.1 at L2-3, 446.8 at L4-5, and 669.9 at L5-S1. The overall percent canal compromise ratio in the surgery group was 46.7%, 44.1% at L4-5, and 49.8% at L5-S1. The overall percent canal compromise in the nonoperative group was 34.2%, 34.1% at L2-3, 36.1% at L4-5, and 31.8% at L5-S1. The percent canal compromise in central herniations at L4-5 level was 53.0% in the surgical group, and 32.8% in the nonoperative group; at the L5-S1 level surgical group percent canal compromise was 64.1% and in the nonoperative group canal compromise was 27%. L4-L5 level paracentral herniations canal compromise was 36.7% in the surgical group compared with 42.5% canal compromise in the nonoperative group. At the L5-S1 level the canal compromise was 45% in the surgical group and 34.8% in the nonoperative group. CONCLUSIONS: Our findings show a trend for patients treated with surgery to have larger disc herniation areas and smaller canal cross-section areas, corresponding to larger percent canal compromise than the nonoperative group. Centrally located herniations followed this trend closely at all levels studied. However, the paracentral herniation at the L4-5 level does not follow this trend, possibly because paracentral disc herniation clinical course is determined more by herniation location rather than the overall herniation size.     

Relaxin down-regulates renal fibroblast function and promotes matrix remodelling in vitro.

BACKGROUND: Renal fibroblasts are important effector cells in tubulointerstitial fibrosis, with experimental antifibrotic strategies focusing on the functional down-regulation of these cells. Several experimental models of fibrosis have provided evidence for the effectiveness of the polypeptide hormone relaxin as a potential antifibrotic agent. This study was conducted to further elucidate the antifibrotic mechanisms of relaxin on renal fibroblasts in vitro. METHODS: Rat cortical fibroblasts were obtained from outgrowth culture of renal tissue isolated from kidneys 3 days post-unilateral ureteric obstruction and constituted 100% of cells studied. A relaxin radio-receptor assay was used to establish binding of relaxin to renal fibroblasts in vitro. Functional studies then examined the effects of H2 relaxin (0, 1, 10 and 100 ng/ml) on fibroblast kinetics, expression of alpha-smooth muscle actin (alpha-SMA), total collagen synthesis, collagenase production and collagen-I lattice contraction. CTGF mRNA expression was also measured by northern analysis. RESULTS: H2 relaxin bound with high affinity to rat renal fibroblasts, but receptor numbers were low. Consistent with its previously reported bimodal effect, transforming growth factor (TGF-beta 1) reduced fibroblast proliferation, an effect abrogated by H2 relaxin. Fibroblasts exposed to H2 relaxin (100 ng/ml) for 24 h demonstrated decreased immunostaining for alpha-SMA and reduced alpha-SMA protein expression compared with controls. There was a trend for a relaxin-mediated reduction in total collagen synthesis and alpha 1(I) mRNA expression with large dose-related increases in collagenase protein expression being observed. TGF-beta 1-stimulated collagen-I lattice contraction was significantly inhibited following co-incubation with 100 ng/ml relaxin. Incremental doses of H2 relaxin had no significant effect on CTGF mRNA expression. CONCLUSIONS: The findings of this study suggest that the antifibrotic effects of relaxin involve down-regulation of fibroblast activity, increase in collagenase synthesis and restructuring of collagen-I lattices, which are consistent with its known physiological role of matrix remodelling. Although there appears to be an interaction between TGF-beta 1 and H2 relaxin, this does not appear to involve a reduction in CTGF mRNA expression.     

Assessment of quality of life in children with peanut allergy

Children with a peanut allergy (PA) are faced with food and social restrictions due to the potentially life-threatening nature of their disease, for which there is no cure or treatment. This inevitably impacts upon their quality of life (QoL). QoL of 20 children with PA and 20 children with insulin-dependent diabetes mellitus (IDDM) was measured using two disease-specific QoL questionnaires (higher scores correspond to a poorer QoL). One questionnaire was designed by us and the other was adapted from the Vespid Allergy QoL questionnaire. We gave subjects cameras to record how their QoL is affected over a 24-h period. Response rates for both questionnaires were 100%. Mean ages were 9.0 and 10.4 years for PA and IDDM subjects, respectively. Children with a PA reported a poorer quality of life than children with IDDM: mean scores were 54.85 for PA subjects and 46.40 for diabetics (p = 0.004) in questionnaire 1 and 54.30 and 34.50 (p≤0.001) in questionnaire 2. PA children reported more fear of an adverse event and more anxiety about eating, especially when eating away from home. Photographs fell into seven common categories: food, management, environment, away from home, physical activities, restaurant and people. Most photographs related to food and management issues and revealed difficulties for both groups regarding food restrictions. PA subjects felt more threatened by potential hazards within their environment, felt more restricted by their PA regarding physical activities, and worried more about being away from home. However, they felt safe when carrying epinephrine kits and were positive about eating at familiar restaurants. The QoL in children with PA is more impaired than in children with IDDM. Their anxiety may be considered useful in some situations, promoting better adherence to allergen avoidance advice and rescue plans.     

Effects of tumor necrosis factor alpha on parathyroid hormone-induced increases in osteoblastic cell cyclic AMP

Summary Tumor necrosis factor α (10⁻¹⁰–10⁻⁸M) had no effects on cyclic AMP production by the osteoblastic osteosarcomal cells, Saos-2 and G292, or normal rat calvarial cells. The cytokine did, however, inhibit the parathyroid hormone (PTH)-induced effect on cyclic AMP in the Saos-2 and normal rat osteoblastic cells. This inhibitory effect did not occur on prostaglandin E₂-induced cyclic AMP increases in the osteoblastic cells. Interleukin-1 (10 U/ml −100 U/ml) did not produce any effect on basal levels or PTH-induced cyclic AMP increases in these cells.