Broadened Allocation of Pancreas Transplants Across Compatible ABO Blood Types.

BACKGROUND: Current Organ Procurement and Transplantation Network (OPTN) policy restricts certain blood type-compatible simultaneous pancreas and kidney (SPK) transplants. Using the Kidney Pancreas Simulated Allocation Model, we examined the effects of 5 alternative allocation sequences that allowed all clinically compatible ABO transplants. METHODS: The study cohort included kidney (KI), SPK, and pancreas alone (PA) candidates waiting for transplant for at least 1 day between January 1, 2010, and December 31, 2010 (full cohort), and kidneys and pancreata recovered for transplant during the same period. Additionally, because the waiting list has shrunk since 2010, the study population was reduced by random sampling to match the volume of the 2015 waiting list (reduced cohort). RESULTS: Compared with the current allocation sequence, R4 and R5 both showed an increase in SPK transplants, a nearly corresponding decrease in KI transplants, and virtually no change in PA transplants. Life-years from transplant and median years of benefit also increased. The distribution of transplants by blood type changed, with more ABO:A, B, and AB transplants performed, and fewer ABO:O across all transplant types (KI, SPK, PA), with the relative percent changes largest for SPK. DISCUSSION: Broadened ABO compatibility allowances primarily benefitted SPK ABO:A and AB candidates. ABO:O candidates saw potentially reduced access to transplant. The simulation results suggest that modifying the current allocation sequence to incorporate broadened ABO compatibility can result in an increase in annual SPK transplants.

CD5-expressing B-cell non-Hodgkin's lymphomas with bcl-1 gene rearrangement have a relatively homogeneous immunophenotype and are associated with an overall poor prognosis.

Mantle cell lymphomas (MCLs) are typically CD5-expressing B-cell non-Hodgkin's lymphomas (NHLs) that frequently harbor the chromosomal translocation t(11;14) or bcl-1 gene rearrangements. Insufficient data are available on the biologic features and clinical behavior of rigorously characterized MCL. As these NHLs have been reported to exhibit various histologic and cytologic expressions, and in order to avoid using somewhat arbitrary and subjective morphologic definitions, we chose to study cases of MCL selected on more objective grounds. Specifically, 15 samples (from 14 patients) of CD5-expressing B-cell NHLs with detectable bcl-1 gene rearrangement were included. Overall, these patients had relatively uniform clinical manifestations. Most were older men (mean age, 67 years) who presented with lymphadenopathy, high-stage disease, and bone marrow involvement. All but two patients relapsed, demonstrated residual tumor, or had disease progression after an initial response to various therapies. Nine patients have died; these patients had a median survival of only 19 months. All cases could be classified within the broad morphologic spectrum previously described for MCL, and no predominant histologic subtype was observed. However, cases could be segregated into two major groups according to tissue architecture: one with a purely diffuse pattern and the other with at least a focal nodular component. Patients with purely diffuse tumors had a lower survival rate (0%) than those with tumors having a nodular component (62% survival rate). In contrast to the morphologic variability, these NHL exhibited a rather homogeneous immunophenotypic pattern. All cases demonstrated intense CD20 expression, with typically intense IgM and light chain expression, and relatively weak IgD expression. In no case was CD10 detected on the neoplastic cells. DNA content analysis showed aneuploidy only in three instances, and two groups of cases could be arbitrarily defined on the basis of their S-phase fraction. A relationship between a purely diffuse growth pattern and a high S-phase fraction (greater than 5%) was observed. As expected from this association, patients with tumors having high S-phase fractions fared worse (14% survival rate) than those patients with tumors showing lower S-phase fractions (57% survival rate). Thirteen NHLs from 12 patients had amplifiable bcl-1 gene rearrangements at the major translocation cluster (MTC). The bcl-1 breakpoints aggregated within a 63-bp region of the MTC, and the amplified tumor DNA from each patient had unique N-nucleotide junctional sequences and Ig joining region breakpoint sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Journals indexed by the AHA Resource Center for Hospital Literature Index and HEALTH database.

The American Hospital Association (AHA) Resource Center indexes journals for the Health Planning and Administration (HEALTH) database and Hospital Literature Index (HLI). These journals, designated special list health journals, are selected to provide access to a wide and balanced coverage of hospital and health care administration and health policy literature. This article provides background information on HEALTH and HLI and describes special list health journals in detail (including historical information, information sources, and broad subject divisions). It also discusses AHA policies relating to journal and article selection and current subject distribution of special list health journals.

Methionine intolerance: a possible risk factor for coronary artery disease.

Homocystinuria, an inherited disorder associated with premature atherosclerosis, represents a severe form of methionine intolerance. To analyze the importance of milder forms of methionine intolerance in the genesis of vascular disease, the relation between provokable methionine intolerance and coronary artery disease was investigated. In a group of 138 men, aged 31 to 65 years (mean 53), referred for cardiac catheterization, plasma homocystine was measured before and 6 hours after an oral l-methionine load (0.1 g/kg). Thirty-nine subjects found to have normal coronary arteries had a mean post-load plasma homocystine level of 0.59 +/- 0.37 mumol/liter. A criterion at the 95th percentile (1.64 SD above the mean) was selected and applied to the remaining 99 subjects with coronary artery disease (0.70 +/- 0.68 mumol/liter). Sixteen (16%) of 99 subjects with coronary artery disease exceeded this level as compared with 1 (2%) of 39 subjects without coronary artery disease (p less than 0.04). The risk of coronary artery disease in men with provokable methionine intolerance was increased sevenfold as estimated by the odds ratio. By correlation matrix and multivariate regression analyses, provokable homocystinemia was predictive of coronary artery disease and was independent of tobacco smoking, hypertension, diabetes mellitus, serum cholesterol and age. It is proposed that men with mild methionine intolerance exposed to the high methionine content of the Western diet may develop intermittent homocystinemia and thus may be at greater risk for the development of coronary artery disease.

Release of nucleosides from canine and human hearts as an index of prior ischemia.

During ischemia, myocardial adenosine triphosphate is degraded to adenosine, inosine and hypoxanthine. These nucleosides are released into coronary venous blood and may provide an index of ischemia; adenosine may also participate in the autoregulation of coronary flow. In dogs, the temporal relations between reactive hyperemic flow and nucleoside concentrations in regional venous blood were correlated after brief occlusions of a segmental coronary artery. Reactive hyperemia and adenosine release peaked together in 10 seconds, persisted for 10 to 30 seconds and then decreased in a pattern consistent with the hypothesis that they are related. During initial reflow after 45 seconds of ischemia, mean concentrations of adenosine, inosine and hypoxanthine increased, respectively, to 52, 67 and 114 nmol/100 ml plasma; after 5 minutes of ischemia, the respective levels increased to 58, 1,570 and 1,134 nmol and fell quickly. In nine patients there was a similar release of nucleosides into coronary sinus blood during reperfusion after 59 to 80 minutes of ischemic arrest during cardiac surgery. With initial reflow, adenosine, inosine and hypoxanthine levels reached 65, 655 and 917 nmol/100 ml of blood, respectively. Inosine and hypoxanthine concentrations remained high for 5 to 10 minutes after cardiac beating resumed, often when production of lactate had decreased. The results indicate that postischemic release of nucleosides reaches significant levels in man as well as animals, is parallel with the duration of ischemia, is temporary and may be a useful supplement to measurement of lactate as an index of prior myocardial ischemia.

Lysosomes in myocardial infarction: studies by means of cytochemistry and subcellular fractionation, with observations on the effects of methylprednisolone.

To evaluate lysosomal involvement in myocardial infarction, coronary artery thrombosis was induced by ligation in 16 dogs. Biopsies of infarcted and normal left ventricles were studied by ultrastructural cytochemistry and subcellular fractionation (0.25 M sucrose) from 30 min to 96 hrs post injury. Normal myocardium contained few "classical" (residual body) lysosomes: instead, acid phosphatase and aryl sulfatase were localized to longitudinal and to lateral sac elements of the sarcoplasmic reticulum. In postnuclear (450 X gm, 10 min) supernates, lysosomal acid phosphatase and beta-glucuronidase were divided 60:40 between sedimentable (98,000 X gm, 15 min) and non-sedimentable fractions of normal endocardium and epicardium (studied separately). At 2 hrs post infarction, ischemic muscle showed: 1) loss of membrane-bound acid phosphatase and aryl sulfatase; 2) mitochondrial damage; 3) loss of glycogen and disappearance of I but not A bands; and 4) entry into cells of colloidal lanthanum (= loss of plasma membrane integrity. Total lysosomal hydrolase did not increase until 6-5 hrs post infarct. At 2 hrs, significant increments (32 +/- 7%) were found in nonsedimentable acid phosphatase and beta-glucuronidase of endocardium (P less than 0.005 vs. normal) but the epicardium. In dogs given methylprednisolone (50 mg/k) 30 min post infarct, ultrastructural cytochemistry showed retention of lysosomal enzymes within endocardial sarcoplasmic reticulum and no significant redistribution of enzymes into non-sedimentable fractions (vs. eight paired, infarcted, untreated controls). Data show early disruption of lysosomes in myocardial infarction and their protection by steroid given after the acute insult.

Cytochemical localization of lysosomal enzyme activity in normal and ischemic dog myocardium.

The effect of ischemia on the integrity of myocardial lysosomes was observed 3 1/2 and 24 hours after the production of infarcts in 20 anesthetized closed-chest dogs by electrically induced thrombosis of the left anterior descending coronary artery. Biopsies from normal, marginal and infarcted areas were fixed and incubated to localize the lysosomal enzymes acid phosphatase and aryl sulphatase. Reaction product in normal cells was localized in small circular or oblong profiles between bundles of myofilaments and adjacent to mitochondria. In addition, curvilinear, membrane-bound profiles containing reaction product were found in close apposition to transverse tubules and near the free margins of the myocardial cells. Thus the distribution of elements of the sarcoplasmic reticulum. Additional reaction product was also seen in residual bodies, on myelin figures, and in the few conventional appearing spherical lysosomes. Little or no acid phosphatase or aryl sulphatase reaction product was seen in the sarcoplasmic reticulum of infarcted myocardium. The degree of cellular degeneration correlated with disappearance of enzyme activity from the sarcoplasmic reticulum and included disruption of membranes and loss of mitochondrial matrix and erosion of I but not A bands. Marginal areas showed variable amounts of cellular degeneration. Separation of myofilament bundles and loss of glycogen correlated with the localized disappearance of acid phosphatase and aryl sulphatase activity in marginal tissue. Disruption of mitochondrial and erosion of I bands correlated with extensive loss of these enzymes. The data suggest that degeneration of myocardial cells following ischemic injury is associated with release of endogenous lysosomal enzymes from the sarcoplasmic reticulum.

Colloidal lanthanum as a marker for impaired plasma membrane permeability in ischemic dog myocardium.

Colloidal lanthanum salts have an average particle size of 40 degrees A; consequently, this electron-opaque marker remains extracellular and does not cross the intact plasma membrane. The affinity of lanthanum for calcium-binding sites on mitochondrial membranes makes it possible to demonstrate loss of plasma membrane integrity at the cellular level in ischemic myocardium. Biopsies were obtained from infarcted, marginal and normal areas 3 1/2 hours after ischemia was produced in 9 anesthetized closed-chest dogs by electrically induced thrombosis of the left anterior descending coronary artery. The tissue was immediately fixed in 4% glutaraldehyde and 0.1 M cacodylate buffer containing 1.3% La(NO3)3, pH 7.4, for 2 hours. In normal control tissue prepared this way the lanthanum tracer, as expected, was confirmed to the extracellular spaces, including, basement membranes, gap junctions and portions of the intercalated discs. Specimens taken near the center of frank infarctions all contained intracellular as well as extracellular lanthanum. Intracellular lanthanum could be seen evenly distributed around lipid droplets and in focal deposits around mitochondria. Only when mitochondria were disrupted did lanthanum gain access to internal sites on mitochondrial membranes. Areas marginal to the infarct contained cells in varying stages of degeneration including many that appeared normal by morphologic criteria alone. Intracellular lanthanum was present in many but not all of the marginal cells in which degenerative changes could be seen. Similarly a few of the cells that appeared morphologically normal contained intracellular lanthanum. The entry of lanthanum into some of these marginal cells and its exclusion from adjacent cells demonstrated that ischemic injury affects the permeability properties of the plasma membrane and independently of other intracellular morphologic changes and that lanthanum can be a sensitive indicator of such alteration in membrane permeability.

Release of adenosine from human hearts during angina induced by rapid atrial pacing.

This study was designed to determine whether human hearts release adenosine, a possible regulator of coronary flow, during temporary myocardial ischemia and, if so, to examine the mechanisms involved. Release of adenosine from canine hearts had been reported during reactive hyperemia following brief coronary occlusion, and we initially confirmed this observation in six dogs hearts. Angina was then produced in 15 patients with anginal syndrome and severe coronary atherosclerosis by rapid atrial pacing during diagnostic studies. In 13 of these patients, adenosine appeared in coronary sinus blood, at a mean level of 40 nmol/100 ml blood (SE = +/-9). In 11 of these 13, adenosine was not detectable in control or recovery samples; when measured, there was concomitant production of lactate and minimal leakage of K(+), but no significant release of creatine phosphokinase, lactic acid dehydrogenase, creatine, or Na(+). THERE WAS NO DETECTABLE RELEASE OF ADENOSINE BY HEARTS DURING PACING OR EXERCISE IN THREE CONTROL GROUPS OF PATIENTS: nine with anginal syndrome and severe coronary atherosclerosis who did not develop angina or produce lactate during rapid pacing, five with normal coronaries and no myocardial disease, and three with normal coronaries but with left ventricular failure. The results indicate that human hearts release significant amounts of adenosine during severe regional myocardial ischemia and anaerobic metabolism. Adenosine release might provide a useful supplementary index of the early effects of ischemia on myocardial metabolism, and might influence regional coronary flow during or after angina pectoris.