Incompatible kidney donor candidates' willingness to participate in donor-exchange and non-directed donation.

Although paired donation, list donation and non-directed donation allow more recipients to receive living donor transplants, policy makers do not know how willing incompatible potential donors are to participate. We surveyed 174 potential donors ruled out for ABO-incompatibility or positive cross-match about their participation willingness. They were more willing to participate in paired donation as compared to list donation where the recipient receives the next deceased donor kidney (63.8% vs. 37.9%, p < 0.001) or non-directed donation (63.8% vs. 12.1%, p < 0.001). Their list donation willingness was greater when their intended recipients moved to the top versus the top 20% of the waiting list (37.9% vs. 19.0%, p < 0.001). Multivariate logistic regression modeling revealed that potential donors' empathy, education level, relationship with their intended recipient and the length of time their intended recipient was on dialysis also affected willingness. For paired donation, close family members of their intended recipient (odds ratio (OR) = 3.01, confidence intervals (CI) = 1.29, 7.02), with high levels of empathy (OR = 2.68, CI = 1.16, 6.21) and less than a college education (OR = 2.67, CI = 1.08, 6.61) were more willing to participate compared to other donors. Extrapolating these levels of willingness nationally, a 1-11% increase in living donation rates yearly (84-711 more transplants) may be possible if donor-exchange programs were available nationwide.

Dobutamine effects on systole and diastole in rats with myocardial infarction.

In this article, the authors attempt to determine the effect of catecholamine stimulation on the systolic and diastolic properties of the left ventricle (LV) in rats with chronic infarction. Male Sprague-Dawley rats underwent coronary artery ligation at 8-10 weeks of age. Baseline hemodynamics were measured 1-2 months after infarction. Dobutamine was administered in bolus injections of increasing concentrations, and peak hemodynamic response after each dose was recorded. Rats were divided into three groups: controls (n = 14), rats with infarct size less than 30% of LV (n = 13), and rats with infarct size at least 30% of LV (n = 9). Baseline hemodynamics were similar among the three groups. There was no significant difference in the maximal response of LV systolic pressure and heart rate between the three groups. Left ventricle +dP/dt increased with dobutamine in all three groups, but rats with infarct size of at least 30% had a significantly smaller increase above baseline as compared with control rats. In contrast, LV -dP/dt increased to a similar degree in all three experimental groups with dobutamine. Although hemodynamics can be affected by loading conditions in the intact animal, the magnitude of the change in +dP/dt with unaltered -dP/dt suggests that there is an impaired inotropic but not lusitropic response to catecholamine stimulation in rats with large chronic myocardial infarcts. The findings imply a differential effect of beta-agonist stimulation on systolic and diastolic properties of the heart.

Contraction band necrosis: its modification by the free radical scavenger N-2-mercaptopropionyl glycine.

Contraction band necrosis (CBN) may represent infarct extension from free radical generation during reperfusion. We sought to limit CBN with the free radical scavenger N-2-mercaptopropionyl glycine (MPG, 20 mg/kg). Sixteen chronically instrumented Beagles (8 control, and 8 MPG treated) underwent 90-min left anterior descending coronary artery (LAD) occlusion followed by 6-h reperfusion. Coronary blood flow (CBF) was measured by the radioactive microsphere technique. The dogs were killed, and the hearts were perfused with red and blue dyes to determine area at risk (AAR), stained with nitroblue tetrazolium for infarct localization, and sectioned for histologic analysis and BF measurements. In controls and MPG-treated animals, infarct/risk ratios were 40 +/- 5 and 38 +/- 6%, and epicardial collateral BFs were 0.21 +/- 0.037 and 0.15 +/- 0.034 ml/g/min, respectively (p = NS). Hemodynamic measurements did not differ between the two groups. However, CBN as a percentage of total infarct was reduced in controls (22 +/- 3%) as compared with MPG-treated animals (35 +/- 2%, p = 0.002). Thus, MPG altered the histologic composition of infarcts in this model, surprisingly increasing the amount of CBN without altering overall infarct size (IS). These results raise questions about the role of free radical scavengers in generation of CBN and suggest that a population of cells exists in which treatment with MPG may alter the mechanism of cell death.

Feasibility of recanalization of human coronary arteries using high-intensity ultrasound.

To investigate the feasibility of ultrasonic recanalization of obstructed human coronary arteries in vitro, high-intensity ultrasound was applied to 16 coronary arteries obtained at autopsy, using a prototype instrument enabling insonification through a catheter tip. It was a 119 cm long, 0.95 mm thick wire in an 8Fr catheter connected to an external ultrasonic transformer and power generator. A 5 MHz phased-array 2-dimensional echocardiography instrument was used to determine minimal luminal diameter and percent diameter narrowing before and after ultrasound application. The ultrasonic energy was delivered at 21.5 kHz and with a 52 +/- 19 micrometer average amplitude of tip displacement. The mean percent luminal diameter narrowing, flow rate and mean pressure gradient before ultrasound exposure were 74 +/- 11%, 97 +/- 61 ml/min, and 92 +/- 18 mm Hg, respectively. After recanalization, the mean percent luminal diameter narrowing decreased to 45 +/- 17% (p < 0.001), the mean flow rate increased to 84 +/- 92 ml/min (p < 0.001), and the mean pressure gradient was reduced to 45 +/- 24 mm Hg (p < 0.001). Of the debris particles, 95% had a diameter < 9 microns (range 5 to 12). Arterial perforation occurred in 5 of 16 arteries (31%) and all 5 occurred due to stiff wire manipulation and without ultrasound application. Mechanical fracture of the wire occurred in 8 cases (50%). No signs of thermal injury were found on histology. Thus, ultrasonic recanalization of human coronary arteries in vitro is feasible. It may reduce obstruction and improve blood flow. Debris sizes are sufficiently small to minimize the hazard of peripheral embolization.

Morphological effects of pulsed ultrasound in the lung.

We have previously described the induction of subcapsular hemorrhage in the murine lung by extracorporeal shock wave lithotripsy at exposures of 2 MPa (Hartman et al. 1990) and pulsed ultrasound (Child et al. 1990). Since extravasation of erythrocytes and alveolar flooding are prominent, we proposed to determine whether or not the injury was progressive, by continuing to develop following termination of exposure, and by localizing where the injury was developing. Mice were exposed to 10 microsecond impulses at 1.6 MPa for 3 min and sacrificed either immediately or 5 min following exposure. When observed with both light and transmission electron microscopy, there was no gradation in lung injury, with a sharp demarcation of the hemorrhagic area. Moreover, both type I pneumocytes and capillary endothelial cells were injured, causing direct continuities between vessel lumina and alveolar spaces. In the absence of extravasation, the tissue appeared normal. There was no evidence that injury increased in severity during the first 5 min after exposure.

Ability of high-intensity ultrasound to ablate human atherosclerotic plaques and minimize debris size.

To investigate whether high-intensity ultrasound can destroy atherosclerotic plaques while sparing the normal arterial wall, 279 normal human aortic sites and 119 fibrous and 193 calcified plaques, obtained from 24 necropsies, were insonified in a water tank, at 20 kHz and at 5 different power intensities, ranging from 68 W/cm2 (P1) to 150 W/cm2 (P5). These intensities were associated with a total excursion of the ultrasound irradiation apparatus tip from 90 to 268 microns, respectively. Time to perforate normal aortic sites and fibrous and calcified plaques was recorded at each intensity. There was no difference in perforation time between normal aortic sites and fibrous and calcified plaques when high-power levels (P2 to P5) were used. However, at the lowest power (P1), perforation time for the normal aortic wall was significantly longer than for fibrous and calcified plaques: 30 +/- 18 seconds (166 observations), 14 +/- 7 seconds (p less than 0.001) (78 observations) and 12 +/- 8 seconds (p less than 0.001) (115 observations), respectively. When perforation times for normal vessel wall versus fibrous plaque and normal vessel wall versus calcified plaque from the same necropsy specimen were compared in a pairwise manner, the results were: 29 +/- 13 vs 16 +/- 7 (p less than 0.001) (48 paired observations) and 26 +/- 9 vs 10 +/- 5 seconds (p less than 0.001) (55 paired observations), respectively. Regardless of whether paired or unpaired comparison was applied, no significant difference was found in perforation time between fibrous and calcified plaques. The debris did not differ in size as measured separately for normal sites and fibrous and calcified plaques by a computer-interfaced Channelizer and Coulter Counter system.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential topographical portrayal of myocardial blood flow.

Methods to portray myocardial blood flow in a two-dimensional continuum are advantageous in that they allow blood flow history to be overlaid on histological or histochemical descriptions of the consequences of ischemia. We describe here autoradiographic methods that allow such portrayals at three separate times during the evolution of ischemic injury. A computer-based image-analysis system was used to derive such flow maps by taking advantage of the physical characteristics of radioactive isotopes.

Fatal multisystem disease with immune enteropathy heralded by juvenile rheumatoid arthritis.

The prognosis of juvenile rheumatoid arthritis (JRA) is generally good, although premature death occurs in a subset of children. Secondary infections, chronic amyloidosis, and heart disease have been reported as common causes. Our experience indicates that JRA can also herald the development of a severe immune enteropathy. In the case presented, typical JRA was followed by fulminant hepatitis; skin rashes; recurrent, severe, watery diarrhea; malabsorption; and ultimately death. Biopsies of the small bowel exposed to the patient's serum revealed deposition of complement and immunoglobulins in the epithelium. Although not widely appreciated, JRA can herald a multisystem syndrome characterized by severe immune enteropathy.

Acoustic microscopy of red blood cells.

We used a scanning acoustic microscope to image normal and outdated red blood cells, cells with different hemoglobin content, red cell ghosts, and cells treated with various drugs that induce echinocyte-stomatocyte transformation. Images were obtained at different planes of focus within the cells, corresponding to maxima and minima of signal intensity. Digitization and gray scale amplitude mapping were used to create axonometric plots that display signal amplitude variations within the cells. The images of red cells contain features produced by differences in topology, density, elasticity, and absorption. Both hemoglobin content and the cell cytoskeleton contribute to image features, and various deformations, characterized by the formation of blebs and vacuoles, are displayed in cells undergoing echinocyte-stomatocyte transformation. These preliminary findings, although mainly descriptive, indicate that acoustic microscopy may be a useful new method for evaluating red cell deformation and associated changes in mechanical properties.

High-frequency attenuation measurements using an acoustic microscope.

An acoustic microscope was used to measure excess attenuation of aqueous solutions of sugars and proteins at 1.0 GHz. Interference pattern spacing and peak amplitude reduction of V(z) curves, obtained with these solutions as the acoustic microscope coupling liquid, were related to the solution wavespeed and attenuation, respectively. Consistent with published results for lower frequencies, solutions with molecular weight greater than 10,000 had a higher specific absorption than those with a molecular weight less than 1000 and within these two molecular weight ranges specific absorption was independent of concentration.

Multicenter validation study of real-time ultrasonography, arteriography, and pathology: pathologic evaluation of carotid endarterectomy specimens.

The morphologic description and measurements of endarterectomy specimens are usually believed to be accurate and are used as the gold standard against which the findings of diagnostic procedures are judged. Pathology data on 289 endarterectomy specimens from five participating centers and the corresponding angiography and B-mode ultrasonography data provided a basis for scrutinizing the validity of using the morphologic measurements as a standard. Discrepancies of greater than 1 mm between pathology and angiography measurements of minimum residual lumen occurred in 35% of the cases and between pathology and B-mode ultrasonography measurements in 64% of the cases. Discrepancies of greater than 1 mm between pathology- and angiography-measured lesion width occurred in 81% of the cases and between pathology and B-mode ultrasonography measurements in 64% of the cases. The cases representing mismatches of greater than 1 mm at one participating center were subjected to a rigorous review, with remeasurement of all morphologic features, in an attempt to explain the discrepancies. Various types of artifactual distortion of the specimens, the presence of slit-like and occluded lumens that were likely related to loss of perfusion pressure, and an inability to match planes of interrogation used in angiography and B-mode ultrasonography with pathology planes contributed significantly to the existence of mismatches. On the other hand, fixation and decalcification produced minimal and insignificant distortional changes. We conclude that the acquisition of quantitative data from endarterectomy specimens and the acceptance of morphologic data as a standard are limited by a number of problems that can be defined but have been difficult to resolve.

Increased plasma IgA, sIgA, and C3- and IgA-containing immune complexes with renal glomerular deposits in diabetic rats.

Male Sprague-Dawley rats were fasted 18 h and given streptozocin (STZ; 60 mg/kg body wt i.p.). The resultant diabetes mellitus, not treated with insulin, was associated with persistent manifoldly increased plasma IgA levels, as measured by single-radial immunodiffusion after reduction with dithiothreitol and alkylation with iodoacetamide. Also observed were concurrent increases in plasma levels of secretory IgA (sIgA) and of C3- and IgA-containing immune complexes (C3-IgA-CIC). After 104 days without insulin treatment, six of the diabetic rats were given daily injections of 2 U of insulin for 11 days. Insulin treatment was associated with a precipitous decrease in plasma levels of IgA, sIgA, and C3-IgA-CIC. Cessation of insulin treatment resulted in restoration of greatly increased levels of all three IgA-containing species. Histoimmunofluorescence studies of kidneys from untreated rats with diabetes of 192-324 days revealed glomerular capillary wall and mesangial deposits reacting strongly with anti-IgA (alpha-chain-specific) antiserum. Kidneys from two of the diabetic rats (324 days) were tested with anti-rat C3 and anti-rat secretory component (SC) antisera, and they reacted positively. Control kidneys from normal rats examined simultaneously were negative. The concurrent changes in plasma levels of three IgA-containing species in the untreated STZ-induced diabetic rat and the demonstration of abnormal immunoreactive IgA-containing renal glomerular deposits make this experiment an attractive model for studying the possible role of disturbed IgA metabolism in the pathogenesis of diabetic nephropathy.

In-vivo measurements of ultrasound attenuation in normal or diseased liver.

Ultrasonic attenuation coefficients of liver have been derived from echoes received by a modified commercial B-scan imaging instrument. Values have been measured from selected regions within liver scans of 59 individuals, of which 15 cases were presumed normal (based on medical histories), and the remainder were involved with diffuse liver disease such as alcoholic cirrhosis, chemotherapy toxicity, chronic hepatitis, and liver metastases. Medical histories on most individuals include the results of serum liver function enzymes, conventional B-scan examinations, and exposure to drugs and alcohol. The results of CT abdominal scans (N = 13) and/or liver biopsy (N = 12) were also available. The results show that normal attenuation values for human liver are 0.054 +/- 0.009 Np/cm-MHz (0.47 dB/cm-MHz) with a frequency dependence of fn, where n = 1.05 +/- 0.25, in agreement with in vitro studies of mammalian liver. In diffuse liver disease, no relationship was found between the attenuation coefficient and the results of CT or conventional ultrasonic examination. A trend towards higher attenuation with increased fibrosis and fat, as graded from liver biopsies, was noted, but the results were generally not statistically significant. However, a significant correlation was found between high values of attenuation and abnormal liver function tests. High attenuation is also found with ingestion of alcohol, chemotherapeutic agents, and steroids, all of which may affect liver composition.

Carotid bifurcation disease: prediction of ulceration with B-mode US.

The presence of carotid ulceration was assessed by two readers for 55 B-mode ultrasound (US) studies. Intact surgical specimens were available for comparison. Ulceration was considered present if the following criteria were obtained: a continuous contour showing focal depression, a well-defined break in the surface 1 mm or more across, a well-defined back wall at the base of the depression, and an anechoic area within the plaque which extended to the surface and was 1 mm or more deep. Using these criteria, the two readers agreed on the diagnosis for 47 studies. When the surgical specimen was used as a reference standard, the accuracy of B-mode US was 60%, its sensitivity was 39%, and its specificity was 72%. Since the impact of scan quality was ruled out by using only scans on which the two readers agreed, the poor results must be attributed to the lack of definitive US criteria. A second review of the scans, with the readers looking only for a heterogeneous echo pattern, revealed that appearance had no higher correlation with ulceration at surgery than any of the original criteria had.

Angiographic and pathologic correlates in carotid artery disease.

Eighty-four consecutive intact atheromata from the carotid bifurcation were examined macroscopically and by standard microscopic techniques. Preoperative angiograms of these cases were reviewed by a single radiologist with special attention to detecting the presence of ulceration. Pathologic and angiographic findings were compared and correlated with the patient's clinical presentation. Macroscopic findings of ulceration were present in 43 cases (51%). Thirty-four specimens contained intramural hemorrhage and 27 showed evidence of mural thrombus. Mural thrombus was significantly associated with evidence of ulceration (p less than 0.01). Intramural hemorrhage was commonly associated with ulceration (25/34) but was also seen in nonulcerated plaques (p greater than 0.05). Angiographic diagnosis of ulceration was made in 54 cases (64%). While angiography identified 78% of macroscopic ulcers (34/43; p = 0.05), seven typical ulcerations were missed angiographically and there were 18 angiographic false positive results (18/54:33%). Macroscopic ulcerations were most common in patients with symptoms of hemispheric ischemia (p less than 0.1). The angiographic diagnosis of ulceration did not correlate with the patient's clinical presentation (i.e., hemispheric ischemia, nonhemispheric ischemia, or asymptomatic stenosis). These results support the thesis that macroscopic ulceration is an important cause of hemispheric ischemia. Angiography does not reliably predict the presence of macroscopic ulceration and this limitation should be kept in mind when patients with hemispheric symptoms are evaluated. Such patients should not be denied consideration for endarterectomy simply because the angiogram fails to demonstrate ulceration.

Pathogenic properties of Campylobacter jejuni: assay and correlation with clinical manifestations.

The pathogenic properties of 20 strains of Campylobacter jejuni isolated from persons with clearly defined clinical manifestations were determined. Cell-free broth filtrates were examined for (i) enterotoxin production by Chinese hamster tissue culture assay and an enzyme-linked immunosorbent assay (ELISA) employing GM1 ganglioside and affinity-purified antiserum to Escherichia coli heat-labile toxin, (ii) cytotoxin production by Vero and HeLa cell tissue culture lines, and (iii) their ability to cause fluid secretion in rat ligated ileal loops. Viable bacteria were examined for invasive properties by an ELISA with the immunoglobulin fraction of antiserum to Formalin-killed bacteria of an invasive strain, and by their effect on fluid secretion and morphology in rat ligated ileal loops. None of the eight isolates obtained from asymptomatic carriers had any detectable pathogenic properties. All six strains isolated from persons with bloody invasive-type diarrhea elaborated a cytotoxin; their viable bacteria had high titers in the ELISA for invasive properties and caused fluid secretion in ligated ileal loops, although consistent morphologic abnormalities and evidence of mucosal invasion, examined by immunofluorescence techniques, were not detected. All six strains isolated from persons with watery secretory-type diarrhea produced an enterotoxin, one elaborated a cytotoxin, and broth filtrates of all strains caused fluid secretion in ligated ileal loops; viable bacteria had low titers in the ELISA for invasive properties and evoked fluid secretion in ligated loops by means of enterotoxin production. These observations show (i) that a correlation exists between the pathogenic properties of the infective C. jejuni strain and gastrointestinal manifestations in the infected host, and (ii) that these pathogenic properties can be identified by in vitro assays, including ELISAs.

Human anticentromere antibodies: distribution, characterization of antigens, and effect on microtubule organization.

Properties of human anticentromere autoantibodies were analyzed. In intact cells or isolated cell fractions, these sera stain the centromeres of mitotic chromosomes and discrete speckles (prekinetochores) in nuclei. Staining is also retained in matrix preparations from nuclei or chromosomes. Immunoprecipitation or immunoblotting demonstrates protein antigens of 14, 20, 23, and 34 kd in HeLa nuclei and chromosomes; immunoprecipitates of nuclei also contain a protein of 15.5 kd. Matrix preparations contain only the 20, 23, and 34 kd species. Absorption of the anticentromere serum with any one of the four nuclear antigens immobilized on nitrocellulose is sufficient to eliminate centromere staining. Using a lysed cell model for microtubule nucleation, anticentromere sera are shown to inhibit specifically the organization of microtubules at the kinetochore.