The haemodynamic effects of iodinated water soluble radiographic contrast media: a review

All classes of iodinated water-soluble radiographic contrast media (RCM) are vasoactive with the iso-osmolar dimers inducing the least changes in the vascular tone. The mechanisms responsible for RCM-induced changes in the vascular tone are not fully understood and could be multifactorial. A direct effect on the vascular smooth muscle cells causing alterations in the ion exchanges across the cell membrane is thought to be an important factor in RCM-induced vasodilatation. The release of the endogenous vasoactive mediators adenosine and endothelin may also play a crucial role in the haemodynamic effects of RCM particularly in the kidney. In addition, the effects of RCM on blood rheology can cause a reduction in the blood flow in the microcirculation. The purpose of this review is to discuss the pathophysiology of the haemodynamic effects of RCM and to offer some insight into the biology of the endothelium and vascular smooth muscle cells as well as the pharmacology of the important vasoactive mediators endothelin and adenosine.     

Determining cephalometric norms for Caucasians and African Americans in Birmingham

The purpose of this study was to establish age- and sex-specific normative data for Caucasians and African Americans in Birmingham, Ala. Subjects (136) between 6 and 18 years old were included in the study. Chang's method (AF-BF) and 12 other measurements were used as determinates of the skeletal sagittal jaw relationship. All subjects had acceptable facial profiles and Class I occlusion. Subjects were divided into eight subgroups based on race, gender, and age. Differences of mean cephalometric values were tested using parametric and nonparametric statistical tests. Compared with Caucasians, African Americans had greater mean values for all measurements except AFB and AF-BF. More negative values were found for the African Americans in the Wits appraisal. Most measurements were found to decrease with age. These findings support our hypothesis that cephalometric norms should be based on racial, sex, and age differences.     

Thromboembolism after foot and ankle surgery. A multicenter study

Thromboembolic disease presents a potentially fatal complication to patients undergoing orthopaedic surgery. Although the incidence after hip and knee surgery has been studied and documented, its incidence after surgery of the foot and ankle is unknown. For this reason, a prospective multicenter study was undertaken to identify patients with clinically evident thromboembolic disease to evaluate potential risk factors. Two thousand seven hundred thirty-three patients were evaluated for preoperative risk factors and postoperative thromboembolic events. There were six clinically significant thromboembolic events, including four nonfatal pulmonary emboli, after foot and ankle surgery. The incidence of deep vein thrombosis was six of 2733 (0.22%) and that of nonfatal pulmonary emboli was four of 2733 (0.15%). Factors found to correlate with an increased incidence of deep vein thrombosis were nonweightbearing status and immobilization after surgery. On the basis of these results, routine prophylaxis for thromboembolic disease after foot and ankle surgery probably is not warranted.     

Autonomic cardiovascular neuropathy in Sj?gren's syndrome. A controlled study

OBJECTIVE: To test patients with primary Sj?gren's syndrome (SS) for evidence of autonomic neuropathy. METHODS: Thirty-two patients with primary SS and 22 age and sex matched healthy individuals were asked specific questions about symptoms suggestive of autonomic neuropathy, and were subjected to a battery of 5 cardiovascular tests: response of blood pressure to sustained hand grip, Valsalva maneuver, heart rate response to deep breathing, and heart rate and blood pressure response to standing up. The chi-squared test with Yates' correction and 95% confidence intervals were used for statistical analysis of the results. RESULTS: Sixteen patients (50%) had symptoms of autonomic neuropathy when specifically asked versus none of the controls (p < 0.0005). The frequency of abnormal responses to the tests was 68.8% in patients and 12.7% in controls (p < 0.0001). Severe autonomic cardiovascular neuropathy was found in 87.5% of the patients but in none of the healthy individuals (p < 0.0001). CONCLUSION: Our results suggest that autonomic neuropathy is a feature of a significant portion of the SS population, and such patients should have appropriate evaluation. Similarly, patients with unexplained autonomic neuropathy should be investigated for evidence of SS.     

Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction

The closely related proto-oncogene proteins CrkII and CrkL consist of one SH2 and two SH3 domains and share 60% overall homology with the highest identity within their functional domains. In this study we show that CrkL and CrkII may play overlapping but different roles in insulin-like growth factor (IGF)-I receptor-mediated signal transduction. While both proteins are substrates involved in IGF-I receptor signaling, they apparently demonstrate important different properties and different biological responses. Evidence supporting this hypothesis includes (a) the oncogenic potential of CrkL versus the absence of this potential in CrkII overexpressing cell lines, (b) the inhibition of IGF-I-dependent cell cycle progression by overexpression of CrkII, and (c) the differential regulation of the phosphorylation status of selective proteins in CrkII and CrkL overexpressing cell lines. In addition we demonstrate the specific association of CrkL and CrkII with the newly characterized IRS-4 protein, again in a differential manner. Whereas CrkL strongly interacts with IRS-4 via its SH2 and N-terminal SH3 domains, CrkII interacts only via its SH2 domain, possibly explaining the unstable nature of IRS-4-CrkII association. The results obtained allow us to propose a unique mechanism of CrkL and CrkII tyrosine phosphorylation in response to IGF-I stimulation. Thus these highly homologous proteins apparently possess structural features that allow for the differential association of each protein with different effector molecules, thereby activating different signaling pathways and resulting in unique biological roles of these proteins.     

Experiences with functional magnetic resonance imaging at 1 tesla

Functional magnetic resonance imaging (fMRI) has been performed on a standard 1 T system using a pulse sequence developed to utilize blood oxygen level dependent (BOLD) contrast and an off-line analysis routine using correlation techniques. The sequence and the data analysis routine have been validated by reproducing the conventional hand movement paradigm studies reported by numerous other workers. Our work has then been extended to investigate cerebral foci for a tonic pain stimulus and the cortical representation of oesophageal stimulation. Both these studies relate to paradigms where the expected BOLD signal is significantly less than that encountered for motor or visual cortex paradigms. The results show good agreement with other modalities (positron emission tomography, magnetoencephalography and cortical evoked potentials). Performing fMRI at 1 T is slightly controversial. However, our successful study of demanding paradigms, using a standard clinical 1 T imaging system, has important implications for many other users operating at this field strength.     

Synthesis and pharmacological evaluation of benzofuran-acetamides as "antineophobic" mitochondrial DBI receptor complex ligands

A sries of novel benzofuran analogues of N,N-di-n-hexyl-2-phenylindole-3-acetamide (5, FGIN-1-27), a potent and highly specific mitochondrial DBI receptor complex ligand, were synthesized by a modified Fischer method and found in vitro and in vivo to be equally potent and selective as FGIN-1-27.     

The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors

BACKGROUND: During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this exposure is of clinical benefit to patients who later receive an allograft as an adult, we analyzed the outcome of primary renal transplantations from sibling donors. METHODS: We retrospectively studied graft survival and rejection episodes in 205 patients who had received renal transplants at nine centers between 1966 and 1996 from sibling donors bearing maternal or paternal HLA antigens not inherited by the recipient. The sibling donors were categorized by analysis of family HLA-typing data. RESULTS: In the multicenter analysis, graft survival was higher at 5 years and at 10 years after transplantation in recipients of kidneys from siblings expressing maternal HLA antigens not inherited by the recipient than in recipients of kidneys from siblings expressing paternal HLA antigens not inherited by the recipient (86 percent vs. 67 percent at 5 years and 77 percent vs. 49 percent at 10 years, P=0.006 for both). Paradoxically, there was a higher incidence of early rejection in the former group, suggesting that fetal and neonatal exposure to maternal antigens results in immunologic priming. Pretransplantation transfusions of donor blood reduced the incidence of acute rejection while preserving the beneficial effect of tolerance to noninherited maternal antigens on graft survival. Since 1986, new immunosuppressive drugs have lessened the short-term, but not the long-term, survival advantage of grafts expressing maternal HLA antigens not inherited by the recipient. CONCLUSIONS: In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.     

Cytogenetic analysis of sister chromosome sets in the second polar body and in pronuclei of unicellular mouse embryos. I. Frequency and origin of aneuploidy in embryos heterozygous for the reciprocal chromosome translocation T[14;15]6Ca]

Matrix metalloproteinases have been implicated to play a vital role in glioma invasion as they degrade extracellular matrix to facilitate the subsequent migration of tumor cells into the surrounding brain tissue. The cytokine Interleukin-10 (IL-10) was detected recently in glial tumors in vivo. Expression of specific IL-10 mRNA as well as blood serum levels of IL-10 in glioma patients increased with malignancy suggesting a functional role of IL-10 in glioma progression. Moreover, glioma cell migration in vitro was enhanced in the presence of IL-10. We therefore investigated the expression of the matrix metalloproteinases (MMPs) stromelysin-1 (MMP-3), 72-kDa collagenase (MMP-2), 92-kDa collagenase (MMP-9), matrilysin (MMP-7) and the human macrophage metalloelastase (MMP-12). In addition, a possible relation between exposure of glioma cells to IL-10 and invasiveness of these cells due to MMP expression was analyzed. Experiments with Matrigel coated Boyden chambers revealed a pronounced dose dependent effect of IL-10 on glioma invasiveness. The synthetic MMP-inhibitor Marimastat markedly reduced cell invasion in the Boyden chambers confirming the significance of MMPs in the process of invasion. Subsequently, the expression level of MMPs and the serine protease uPA was investigated in 7 glioma cell lines (U373, GaMG, U251, GHE, SNB19, U138 and D54) by RT-PCR. In all but one cell line no enhancement of MMP expression by IL-10 was detected. Matrilysin in U373 cells was the only protease found to be upregulated in the presence of IL-10 dependent on cell density. The present data suggest that IL-10 related effects on the invasive properties of the cell lines are not directly mediated by an upregulation of matrix metalloproteinase expression.     

Temporal variability of vena contracta and jet areas with color Doppler in aortic regurgitation: a chronic animal model study

OBJECTIVE: The purpose of our study was to determine the temporal variability of regurgitant color Doppler jet areas and the width of the color Doppler imaged vena contracta for evaluating the severity of aortic regurgitation. METHODS: Twenty-nine hemodynamically different states were obtained pharmacologically in 8 sheep 20 weeks after surgery to produce aortic regurgitation. Aortic regurgitation was quantified by peak and mean regurgitant flow rates, regurgitant stroke volumes, and regurgitant fractions determined using pulmonary and aortic electromagnetic flow probes and meters balanced against each other. The regurgitant jet areas and the widths of color Doppler imaged vena contracta were measured at 4 different times during diastole to determine the temporal variability of this parameter. RESULTS: When measured at 4 different temporal points in diastole, a significant change was observed in the size of the color Doppler imaged regurgitant jet (percent of difference: from 31.1% to 904%; 233% +/- 245%). Simple linear regression analysis between each color jet area at 4 different periods in diastole and flow meter-based severity of the aortic regurgitation showed only weak correlation (0.23 < r < 0.49). In contrast, for most conditions only a slight change was observed in the width of the color Doppler imaged vena contracta during the diastolic regurgitant period (percent of difference, vena contracta: from 2.4% to 12.9%, 5.8% +/- 3.2%). In addition, for each period the width of the color Doppler imaged vena contracta at the 4 different time periods in diastole correlated quite strongly with volumetric measures of the severity of aortic regurgitation (0.81 < r < 0.90) and with the instantaneous flow rate for the corresponding period (0.85 < r < 0.87). CONCLUSIONS: Color Doppler imaged vena contracta may provide a simple, practical, and accurate method for quantifying aortic regurgitation, even when using a single frame color Doppler flow mapping image.