Long-term follow-up of renal function in recipients and donors following pediatric kidney transplantation

Of 125 children undergoing kidney transplantation (tx), 87 received their grafts from living donors. Renal function of recipients (R) and donors (D) was assessed by glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) determined by clearances of inulin and para-aminohippuric acid. Rs were investigated yearly and Ds on alternate years. Within 5 months of tx, absolute GFR and ERPF (ml/min) were significantly lower in R than in D, and the differences in absolute GFR and ERPF between D and R were directly related to the difference in body surface area (BSA) between the two subjects. R and D pairs were repeatedly followed for 4, 6, and 8 years and the absolute GFR of R did not change during follow-up, while relative GFR decreased. Relative GFR decreased most in R, with the greatest difference in BSA between D and R at tx. In the donors, however, both absolute and relative GFR increased significantly up to 8 years. In conclusion, renal function of the two kidneys from the donor, i.e., the grafted kidney in the R and the single native kidney of the D, differed. The native kidney showed a capacity to increase its absolute and relative function with time. The grafted kidney, however, did not show an increase in absolute GFR, resulting in decrease in relative GFR, and the greater difference in BSA between D and R at tx, the greater fall in relative GFR of the R. Received: 7 June 2001 / Revised: 30 July 2001 / Accepted: 30 July 2001     

Rapid decreases in donor-specific cytotoxic T lymphocyte precursor frequencies and graft outcome after liver and lung transplantation

BACKGROUND: A decrease in donor-specific T cell precursor frequencies as seen late, one or more years, after transplantation is assumed to reflect transplantation tolerance, a condition important for long term acceptance of the allograft. However, such late decreases also occur in recipients that developed chronic transplant dysfunction questioning its relevance in transplantation tolerance. We investigated whether early, i.e., the first 6 months, decreases in donor-specific T cell precursor frequencies reflect transplantation tolerance and predict graft outcome after liver and lung transplantation. METHODS: Donor and third party specific cytotoxic (CTLp) and helper T lymphocyte precursor (HTLp) frequencies were analyzed in pretransplant and 1 (or 2) and 6-month blood samples taken from liver and lung recipients and were correlated with graft outcome. RESULTS: In liver allograft recipients with good graft function (n=7), mean donor-specific CTLp frequencies decreased as early as 1 month after transplantation and remained low thereafter. In contrast, mean CTLp frequencies did not decrease in liver allograft recipients with chronic transplant dysfunction (n=6). In lung allograft recipients, donor-specific CTLp frequencies remained relatively high and frequencies were not different between recipients without (n=6) or with (n=6) chronic transplant dysfunction. Donor-specific HTLp frequencies did not change significantly after liver or lung transplantation and did not differ between recipients without or with chronic transplant dysfunction. CONCLUSIONS: An early decrease in donor-specific CTLp correlates with good graft outcome after liver transplantation. Such rapid decreases in alloreactivity do not occur after lung transplantation illustrating the unique capacity of liver allografts to induce transplantation tolerance.     

Dose- and time-dependent formation of biliary benzo[a]pyrene metabolites in the marine flatfish dab (Limanda limanda)

Polycyclic aromatic hydrocarbons (PAHs) are abundant pollutants, and many PAHs are carcinogenic, but only after metabolic activation. Benzo[a]pyrene (BaP) is among the most carcinogenic PAHs. The dose and time response of two enzymes involved in BaP metabolism and the amounts of BaP metabolites excreted into the bile were evaluated in an experiment with dab (Limanda limanda). Ninety dab were exposed orally to one of five doses of BaP (0, 0.08, 0.4, 2, or 10 mg/kg) and sampled at 3, 6, or 12 d after exposure. None of the doses studied caused significant induction of either microsomal ethoxyresorufin-O-deethylase (EROD). which reflects cytochrome P450 1A (CYP1A) activity, or cytosolic glutathione-S-transferase activity (GST). Concentrations of biliary BaP metabolites significantly increased with dose and significantly decreased with time after exposure. It is concluded that biliary BaP metabolites provide a much more sensitive method than EROD (CYP1A) or GST activity to monitor recent exposure to PAHs in dab.     

Genotypic analysis of Staphylococcus aureus from milk of dairy cows with mastitis in Argentina

Staphylococcus aureus is the most prevalent pathogen causing mastitis of dairy ruminants. This study was developed to ascertain the genotypes and genealogical relationship among strains isolated from milk of bovines with mastitis in Argentina. Molecular epidemiological analysis of S. aureus was performed on 112 isolates from 21 districts. Clonality was assessed by SmaI pulsed-field gel electrophoresis (PFGE) typing, automated EcoRI ribotyping and restriction enzyme analysis of plasmid (REAP) DNA profiles. A total of 22 band patterns distributed in four clusters were found by SmaI PFGE analysis. The similarity of clusters 2, 3 and 4 with cluster 1 was 0.73, 0.69 and 0.33, respectively, and 101 of 112 isolates belonged in cluster 1. PFGE band patterns from 42 isolates within cluster I were indistinguishable from each other (type A). The second largest group of isolates with indistinguishable PFGE band patterns was subtype A11, which was composed of 19 isolates. Automated ribotyping assigned the 112 isolates into 13 ribotypes. Among these, the most prevalent ribotypes I and VI were composed of 49 and 35 isolates respectively. Although there was certain correspondence between PFGE genotypes and ribotypes, further discrimination was achieved by combining both methods. REAP DNA profile analysis was useful to provide even further discrimination between isolates with identical PFGE genotype and ribotype. The most prevalent S. aureus strains A/I and A11/VI were widely distributed in the country and were not restricted to individual nearby locations. Prevalence of these two strains varied consecutively within a period of 8 years. Whether the shift in type prevalence was due to selection of a phenotypic trait remains undisclosed.     

Case of 45,X/46,XY mosaicism with non-mosaic discordance between short-term villi (45,X) and cultured villi (46,XY)

We report on a prenatally detected case of discordant non-mosaic karyotypes following chorionic villus sampling. A 45,X karyotype was found in cytotrophoblast cells and a 46,XY karyotype in mesenchymal core cells. A subsequent amniocentesis showed a true 45,X/46,XY mosaicism. Confirmatory studies, including fluorescence in situ hybridization (FISH) in various fetal and placental tissues as well as in the original villi preparations changed the presumed condition of generalized mosaicism with culture confined normality to that of generalized mosaicism with absolute concordance. This case underscores the importance of the investigation of both short-term and cultured villi preparations, the implementation of prenatal FISH studies, and the need for thorough follow-up investigation in cases of discrepant results.     

Differential expression of carnosine, homocarnosine and N-acetyl-L-histidine hydrolytic activities in cultured rat macroglial cells

N-acetyl-L-histidine (NAH) and N-acetyl-L-aspartate (NAA) are representatives of two series of substances that are synthesized by neurons and other cells in the vertebrate central nervous system (CNS). Histidine containing homologs of NAH are β-alanyl-L-histidine or carnosine (Carn) and γ-aminobutyrl-L-histidine or homocarnosine (Hcarn). A homolog of NAA is N-acetylaspartylglutamate (NAAG). These substances belong to a unique group of osmolytes in that they are synthesized in cells that may not to be able to hydrolyze them, and are released in a regulated fashion to a second compartment where they can be rapidly hydrolyzed. In this investigation, the catabolic activities for NAH, Carn, and Hcarn in cultured macroglial cells and neurons have been measured, and the second compartment for NAH and Hcarn has been identified only with astrocytes. In addition, oligodendrocytes can only hydrolyze Carn, although Carn can also be hydrolyzed by astrocytes. Thus, astrocytes express hydrolytic activity against all three substrates, but oligodendrocytes can only act on Carn. The cellular separation of these hydrolytic enzyme activities, and the possible nature of the enzymes involved are discussed.     

Neuroimaging abnormalities in children with an apparent first unprovoked seizure

OBJECTIVE: To determine the incidence and type of neuroimaging abnormalities in children presenting with a first seizure. METHODS: In a prospective observational study, 411 children with a first afebrile seizure were seen between 1983 and 1992. Imaging studies were performed in 218 (53%). For this analysis we examined the most sensitive neuroimaging study performed which included 159 computed tomography scans and 59 magnetic resonance imagings (MRI). RESULTS: Four children were found to have lesions requiring intervention (brain tumor in two, neurocysticercosis in two). The remaining 407 were enrolled in a follow-up study of children with a first unprovoked seizure. After a mean follow-up of >10 years, none have developed clinical evidence of a tumor. In these 411 children, 45 (21%) of 218 imaging studies were abnormal. The most common abnormalities were focal encephalomalacia (n=16) and cerebral dysgenesis (n=11). Although children with partial seizures were more likely to be imaged (64%) than children with generalized seizures (43%) (P<0.001), the fraction of abnormal imaging studies was similar in both groups. Six children with a normal neurological examination who were initially classified as cryptogenic were subsequently found to have errors of cerebral migration on MRI. The incidence of lesions requiring acute intervention in children presenting with a first seizure is low. A significant proportion will have neuroimaging abnormalities particularly on MRI. CONCLUSIONS: Neuroimaging should be considered in any child with a first seizure who does not have an idiopathic form of epilepsy.     

Recurrent infectious mononucleosis caused by Epstein-Barr virus with persistent splenomegaly

We present the clinical case of a 20-year-old male soldier who appeared in general good physical condition. He suffered from infectious mononucleosis caused by Epstein-Barr virus that had recurred 2 years after the first serologically documented episode. The detected splenomegaly persisted in the healthy young man, who otherwise showed no apparent immune deficiency. To our knowledge, this is an extremely rare condition.     

Cardiovascular effects of verapamil and quinidine at normal and elevated ambient pressure

Cardiovascular parameters were measured in rats before and after administration of verapamil and quinidine, a slow Ca2+ and fast Na+ channel blocker, respectively, at normal and elevated ambient pressure [5 bar (500 kPa)]. Left ventricular pressure (Pivt), maximal velocity of Plvt rise (+dP/dt) and fall (-dP/dt), and heart rate (HR), arterial systolic pressure (Pasys), and mean arterial pressure (MAP) were measured in all animals using catheters connected to pressure transducers. Cardiac output (Q), and myocardial blood flow (MBF) were detected by the microsphere technique. Total peripheral vascular resistance (TPVR), myocardial vascular resistance (MVR) and oxygen consumption of the heart (VO2) was calculated. In Groups 1a (control group; 1 bar) and 1b (test group; 1-5 bar), verapamil (1.5 mg x kg(-1)) caused a reduction in Plvt, +dP/dt, -dP/dt, Pasys, MAP, VO2, TPVR, and MVR in both groups at 1 bar (100 kPa), and these parameters remained depressed for at least 50 min in Group 1a. However, MBF increased after verapamil injection. After compression to 5 bar (500 kPa), Plvt, dP/dt, Pasys, VO2, and MBF were markedly elevated (Group 1b). No change in HR, SV, or Q was found in either of the groups. In Groups 2a (control group; 1 bar) and 2b (test group; 1-5 bar), quinidine (5 mg x kg(-1)), infused over a period of 10 min, reduced Plvt, +dP/dt, -dP/dt, MAP, Pasys, VO2, Q, stroke volume (SV), TPVR and MBF at 1 bar (100 kPa). These parameters remained depressed for almost the whole experimental period in Group 2a, while Plvt, +/-dP/dt, Pasys, MAP and VO2 were enhanced during exposure to 5 bar (500 kPa) in Group 2b. The HR was unchanged by quinidine in Group 2a, but was increased at elevated ambient pressure in Group 2b, whereas the MBF was unchanged in both groups. The present results show that verapamil and quinidine have a depressant effect on cardiac function, arterial pressure and VO2 at normal atmospheric pressure, whereas MBF was enhanced only in the verapamil group. During exposure to elevated ambient pressure, cardiac function, arterial pressure and VO2 increased despite adequate inhibition of slow Ca2+ and fast Na+ channels.