Pulsatile Perfusion Reduces the Incidence of Delayed Graft Function in Expanded Criteria Donor Kidney Transplantation

The use of expanded criteria donors (ECD) has been proposed to help combat the discrepancy between organ availability and need. ECD kidneys are associated with delayed graft function (DGF) and worse long-term survival. The aim of this study is to evaluate the impact of pulsatile perfusion (PP) on DGF and graft survival in transplanted ECD kidneys. From January 2000 to December 2003, 4618 ECD kidney-alone transplants were reported to the United Network for Organ Sharing. PP was performed on 912 renal allografts. The prognostic factors of DGF were analyzed using multivariate logistic regression analysis. Risk factors for reduced allograft viability were greater in donors and recipients of PP kidneys. Three-year graft survival of ECD kidneys preserved with PP was similar to cold storage (CS) kidneys. The incidence of DGF in PP kidneys was significantly lower than CS kidneys (26% vs. 36%, p < 0.001). Despite having a greater number of risk factors for reduced graft viability, the ECD-PP kidneys had similar graft survival compared to ECD-CS kidneys. The use of PP, by decreasing the incidence of DGF, may possibly lead to lower overall costs and increased utilization of donor kidneys.     

A primary lung carcinoma producing alpha-fetoprotein, carcinoembryonic antigen, and human chorionic gonadotropin. Immunohistochemical and biochemical studies

This article documents a patient with lung carcinoma that produced three oncofetal antigens including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (hCG). Serum AFP, CEA, and hCG-beta-subunit were extremely high--118,000 ng/ml, 133 ng/ml and 0.9 ng/ml, respectively. Immunohistochemical staining of these tumor markers revealed that these proteins were present in different cells. The pattern of lectin affinity electrophoresis of AFP resembled that of hepatocellular carcinoma. Also investigated was the reactivity of serum CEA to monoclonal antibodies against peptide or sugar moieties. Serum CEA values measured by antipeptide monoclonal antibodies were higher than those measured by antisugar monoclonal antibodies. The demonstration of AFP, CEA, and hCG in different tumor cells suggests that three genomes were not reactivated together in a cell, and the lung carcinoma probably consisted of at least three clones of cancer cells with different phenotypes.     

Blocking effect of 1389-S on the sodium current in isolated guinea-pig ventricular myocytes

Under whole cell patch conditions, 1389-S blocked the INa in guinea-pig ventricular myocytes under steady state conditions (Kdrest = 30 microM, Kdi = 2.4 microM) with a shift of the inactivation curve to the hyperpolarizing direction. Both brief and long conditioning pulses could produce a use-dependent block of 1389-S. These results suggest that 1389-S had a higher affinity to the inactivated than to the rested state under steady state conditions and had a higher affinity to the activated state during train pulses as well as to the inactivated state, making channels unavailable for conduction upon activation.     

A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture

The effect of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), a novel cognition enhancer, on adenylate cyclase activity was investigated in cultured neurons of the mouse cerebral cortex. NS-105 (10^–7 and 10^–6 M) inhibited forskolin-stimulated cyclic AMP formation, an action that was dependent on pertussis toxin-sensitive G proteins. Conversely, in pertussis toxin-pretreated neurons, NS-105 (10^–7 –10^–5 M) significantly enhanced the forskolin-stimulated cyclic AMP formation, and this action was completely reversed by cholera toxin. A metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S, 3R-ACPD) produced similar bi-directional actions on the cyclic AMP formation. Both of these inhibitory and facilitatory actions of NS-105 and 1S, 3R-ACPD were blocked by L(+)-2-amino-3-phosphopropinoic acid (L-AP3). NS-105 (10^–6 M) and 1S, 3R-ACPD (10^–4 M) significantly enhanced isoproterenol- and adenosine-stimulated cyclic AMP formation. The enhancement of such Gs-coupled receptor agonists-stimulated cyclic AMP formation was also produced by quisqualate but not by L(+)-2-amino-4-phosphonobutanoate (L-AP4). The phosphoinositides hydrolysis was enhanced by 1S, 3R-ACPD (10^–4 M) but not by NS-105 (10^–6 M), however, 1S, 3R-ACPD-induced increase in phosphoinositides turnover was attenuated by NS-105. These findings suggest that NS-105 stimulates metabotropic glutamate receptor subclasses that are coupled both negatively and positively to adenylate cyclase, but it acts as an antagonist at the receptor subclasses that are linked to phosphoinositides hydrolysis. Received: 3 February 1997 / Accepted: 25 April 1997     

Chondrons from articular cartilage. III. Morphologic changes in the cellular microenvironment of chondrons isolated from osteoarthritic cartilage

Chondrons were isolated from human and canine osteoarthritic cartilage using low-speed homogenization techniques. Changes in chondron morphology were evaluated using differential interference-contrast microscopy, phase-contrast microscopy, and histochemical and ultrastructural methods. Chondrocyte viability was assessed using fluorescein diacetate staining, and chondron metabolism was investigated using autoradiography. The results suggest that initial changes in the collagen and proteoglycan distribution within the chondron are followed by chondrocyte proliferation to form clusters. These techniques offer the potential to study cell matrix interactions in degenerative osteoarthritis.     

The effect of glycerol on EEG-abnormality (polymorphic delta wave) in patients with brain tumors

The effect of intravenous infusion of 10% glycerol on polymorphic delta waves of EEG was investigated in 13 patients (15 studies) with brain tumors in cerebral hemisphere. The delta waves were analyzed by two-dimensional EEG topography and power spectrum of delta waves (P(delta)) over the tumor, adjacent, and distant regions in the same hemisphere to the tumor, and ipsi- and contralateral hemispheres to the tumor. The data focus of EEG topography was well corresponded to the tumor and surrounding brain edema which visualized by x-ray CT-scan. In the patient with brain tumors with marked brain edema (group A, 11 studies), EEG topography showed marked reduction of delta focus within 20 minutes from the end of intravenous infusion of glycerol, and returned to preinfusion distribution within 60 minutes. In patients with absent to minimum brain edema (group B, 4 studies), delta focus showed the tendency to enlarge and returned to preinfusion state at 60 minutes after the end of glycerol infusion. In patients of group A, P(delta) of ipsilateral hemisphere to tumor decreased at the end of glycerol infusion, and showing maximal reduction ratio (30%, p less than 0.01) at 20 minutes, re-increased there-after. In group B, P(delta) of ipsilateral hemisphere showed no definite changes after the glycerol infusion. P(delta) of contralateral hemispheres in patients of both group A and B, showed similar reduction ratio and time course to those of ipsilateral hemisphere of group A.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of caffeine on expression of cardiac myosin heavy chain gene in adult hypothyroid and fetal rats.

Changes in cardiac myosin heavy chain (MHC) gene expression and isozyme transitions have been shown to be caused by developmental changes, hemodynamic overload, or the activity of various hormones. In this study, to examine whether caffeine, which has teratogenic effects on the fetal cardiovascular system, causes the distribution of cardiac MHC phenotype and, if so, to evaluate the mechanisms of the distribution of cardiac MHC phenotype by caffeine, we examined the effects of caffeine, theophylline, and cAMP on the cardiac MHC isoform transitions at the gene and protein levels using hypothyroid adult rats. Furthermore, we examined the expression of alpha- and beta-MHC gene in cardiac muscles of fetuses whose dams had received caffeine. The results showed that caffeine, theophylline, and cAMP caused accumulations of alpha-MHC mRNA and MHC isozyme V1. Furthermore, in the fetal hearts, it was recognized that caffeine induced an accumulation of alpha-MHC gene expression, as was also seen in the dams. However, this effect of caffeine on the heart was stronger in the fetus than in the dam. Intracellular cAMP concentration was increased by the administration of caffeine, theophylline, or cAMP, and the levels showed a positive correlation with those of alpha-MHC mRNA. These results suggest that the induction of alpha-MHC mRNA expression by the administration of caffeine may be induced by an increase in intracellular cAMP concentration.     

Velamentous cord insertion into the lower third of the uterus is associated with intrapartum fetal heart rate abnormalities.

OBJECTIVES: To evaluate the accuracy of sonographic identification of the site of umbilical cord insertion (CI) at 18-20 weeks of gestation, to compare the sensitivities for detection of a velamentous cord insertion (VCI) secondary to a CI into the anterior, posterior or fundal wall, and to compare the intrapartum complications secondary to VCI into the upper, middle or lower third of the uterus. METHODS: As part of the routine ultrasound scan at 18-20 weeks' gestation we evaluated abnormal CI (VCI and marginal CI) and the location of the CI in the uterus in 3446 pregnancies. In cases of abnormal CI, the location of the CI was further classified as being in the upper, middle or lower third of the uterus. After delivery, the placenta and the umbilical cord were examined and intrapartum complications were compared with the location of the CI. RESULTS: The values for antenatal detection of VCI were: sensitivity, 25 of 40 (62.5%); positive predictive value, 25 of 25 (100%); and negative predictive value, 3406 of 3421 (99.6%). The sensitivity for cases in which the CI was located on the anterior wall was 12 of 13 (92.3%); when it was located on the posterior wall, the sensitivity was 11 of 22 (50.0%); and when it was fundal the sensitivity was 2 of 5 (40.0%). Variable decelerations were frequently observed with a VCI. In lower VCI cases, non-reassuring fetal heart rate patterns and emergency Cesarean sections occurred with a higher frequency than in cases with upper or middle VCI (P < 0.01). After delivery, the length of the aberrant vessels in cases of VCI by pathologic examination was 3.9 +/- 3.3 cm in the upper third, 4.7 +/- 4.6 cm in the middle third, and 10.6 +/- 6.8 cm in the lower third; thus, the aberrant vessel length was significantly greater when the CI was in the lower third of the uterus (P = 0.024). CONCLUSION: We have demonstrated that VCI with a lower CI site and with longer aberrant vessels is associated with various intrapartum complications. This finding has the potential for improving perinatal outcome.     

Radionuclide cardiac volumes: effects of region of interest selection and correction for Compton scatter using a buildup factor.

The effects of region of interest (ROI) selection and correction for Compton-scattered photons using a buildup factor on radionuclide left ventricular volumes calculated by the Links method were compared in 19 humans with contrast ventriculography and in phantoms. Three different methods of ROI selection were compared: a manual ROI, a second derivative ROI and a 50% count-threshold ROI. In phantoms without Compton scatter correction, volumes were overestimated by 30% (manual ROI), 20% (derivative ROI) and 1% (count threshold ROI). In subjects, results without Compton scatter correction were similar with overestimates of 50% (manual ROI) and 20% (derivative ROI) and an underestimate by 3% (count threshold method). Correction for Compton-scattered photons with the use of a phantom-derived buildup factor resulted in improved accuracy for the manual ROI (+15%) and the derivative ROI (0%). A 50% count threshold ROI following interpolative background subtraction allows the accurate calculation of cardiac volumes without the need for scatter correction, while a second derivative ROI method requires a correction for Compton scatter with the use of a buildup factor.