Important risk factors of allograft survival in cadaveric renal transplantation. A study of 426 patients.

Multiple risk factors contribute to the allograft survival of patients who have cadaveric renal transplantation. A retrospective review of 19 such factors in 426 patients identified race, DR match, B + DR match, number of transplants, and preservation time to have a significant influence. The parametric analysis confirmed the effect to be primarily in the early phase, i.e., first 6 months. All patients received cyclosporine with other methods of immunosuppression resulting in an overall 1-year graft survival rate of 66%. The overall 1-year graft survival rate in the white race was 73% and in the black race was 57% (p = 0.002). Allograft survival and DR match showed white recipients with a 1 DR match to have 75% survival at 1 year compared with 57% in the black patient (p = 0.009). If HLA B + DR match was considered, the white recipient allograft survival increased to 76%, 84%, and 88% for 1, 2, and 3 match kidneys by parametric analysis. Patients receiving first grafts had better graft survival (68%) than those undergoing retransplantation (58%) (p = 0.05). Organ preservation less than 12 hours influenced allograft survival with a 78% 1-year survival rate compared with 63% for kidneys with 12-18 hours of preservation. Despite the benefits of B + DR typing, short preservation time, and first transplants to the white recipient, the allograft survival in the black recipient remained uninfluenced by these parameters.     

Benefits of quadruple immunosuppressive therapy in recipients of living related donor kidneys. A review of 855 operations.

Eight hundred fifty-five living related donor transplant recipients were analyzed according to 15 potential risk factors with regard to patient and graft survival according to immunosuppression. Group I, 1968 to 1983, (n = 440 patients) received azathioprine and prednisone; group II, 1984 to 1987, (n = 229 patients) received triple therapy--azathioprine, prednisone, and cyclosporine; and group III, 1988-1991, (n = 186 patients), quadruple therapy--azathioprine, prednisone, cyclosporine, and Minnesota antilymphocyte globulin. Three important risk factors included immunosuppression, tissue typing, and race. Groups II and III had improved allograft survival over group I (p = 0.03). Patients with two haplotype matches had similar survival in all three groups. Kidney survival in one-haplotype-matched recipients improved in group II and was equal to that of the two-haplotype-matched patients in group III. Cyclosporine improved allograft survival in both races when combined with azathioprine and prednisone. Quadruple therapy improved early survival in one-haplotype black patients, even though long-term results remained better in whites. Cyclosporine did not improve graft survival in two-haplotype recipients. The addition of cyclosporine and quadruple therapy did not increase morbidity and mortality rates.     

Dendritic development and preferential growth into synaptogenic fields: a quantitative study of Golgi-impregnated spinal motor neurons

Branching patterns of dendrites may be modulated by the way in which dendritic growth cone filopodia come into initial synaptic relationships with afferent axons. This synaptotropic hypothesis of dendritic branching predicts that dendritic growth will be directed preferentially into regions containing numerous prospective presynaptic elements. The developing mouse spinal cord provides a natural experiment to test this prediction, because synapses are found exclusively within the marginal zones bordering the motor columns during the early (E11-14) period of synaptogenesis. During this time, therefore, most motor dendritic growth would be expected to be directed laterally or ventrally into the marginal zones, whereas internally directed growth should become more prevalent later, when synaptogenesis begins to take place within the intermediate zone, i.e., the motor columns proper. A computer-assisted three dimensional reconstruction system has been used to test these expectations in Golgi preparations of developing mouse (C57BL/6J) spinal cords ranging in age from E13 through P1. Mean dendritic lengths and branch densities are significantly greater for marginal zone dendrites than for intermediate zone dendrites at early ages (E13-14), but there are no significant differences in these measures at later stages of development (P0,1). These findings are interpreted as meaning that motor dendritic growth is initially biased into the marginal zone by synaptogenic afferents and that this preferential distribution is progressively lost as synapses develop within the intermediate zone to attract or to stabilize internally directed dendritic growth. Thus the findings of this study are consistent with predictions of the synaptotropic hypothesis of dendritic branching.     

Genetic toxicology testing of Di(2-ethylhexyl) terephthalate

Di(2-ethylhexyl) terephthalate (DEHT) is a commercially produced chemical (Kodaflex® DOTP) that is used as a general purpose, low-volatility plasticizer for polyvinyl chloride and other polymeric materials. Less than 30 million kilograms of DEHT are produced annually. DEHT is isomeric with di(2-ethylhexyl) phthalate (DEHP), a nongenotoxic rodent carcinogen whose mode of action has been suggested to derive from its ability to produce hepatocellular proliferation and/or hepatic peroxisome proliferation. Thus it is important to know the behavior of DEHT in genotoxicity assays in order to compare it with that of DEHP and other phthalate ester plasticizers. It is known from previously published studies that rats fed DEHT in the diet at 2,000 mg/kg produce urine that is negative in the Ames Salmonella bacterial mutagenicity assay in the presence and absence of induced rat liver S-9 and in the presence and obsence of β-glucuronidase/aryl sulfatase. Reported here are the results of direct testing of DEHT in the Ames plate incorporation assay, the Chinese hamster ovary/hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT) in vitro mammalian cell mutagenicity assay, and an in vitro chromosome aberrations assay using CHO cells. The results for mono(ethylhexyl) terephthalate (MEHT), a metabolite of DEHT, in the Ames Salmonella bacterial mutagenicity assay are also presented. All test results for both DEHT and MEHT were found to be negative, and it is therefore concluded that DEHT, like its isomeric relative DEHP, is not genotoxic. © 1994 Wiley-Liss, Inc.     

Pigmentary changes in rat oral mucosa following antimalarial therapy

Pharmacogenic pigmentation of the oral mucosa has been reported following the use of a number of anti-malarial drugs. The nature and distribution of the pigment is inconclusive in the literature. The aim of the present study was to document pigment deposition within the oral mucosa of DA rats following prolonged chloroquine and pyrimethamine administration. The drugs were given as a combined dosage and separately to different groups via stomach gavage tube. After 12 weekly administrations the palatal mucosa was examined histochemically and ultrastructurally for changes in numbers and size of active melanocytes using the dopa-oxidase technique. The serum was analysed for changes in ACTH and testosterone levels. Morphometric analysis of cells incubated for dopa-oxidase showed a significant increase in the size of dopa positive cells with both drugs but an increase in the number of active melanocytes with chloroquine only. Serum levels of ACTH remained unchanged with both drugs but pyrimethamine caused an elevation in testosterone.     

New reference allelic ladders to improve allelic designation in a multiplex STR system

This paper reports the composition of a new reference allelic ladder mixture for use with a multiplex DNA profiling system consisting of six short tandem repeat loci. The loci included in this mixture are HUMTH01, D21S11, D18S51, D8S1179, HUMVWAF31/A, HUMFIBRA/FGA and an amelogenin sex test. Sequence analysis of individual ladder alleles was carried out and allelic designations made in accordance with the recommendations of the International Society of Forensic Haemogenetics (1992; 1994). A series of rare alleles which increase the range of alleles previously reported were identified. By including some of the rare alleles into the ladder marker system, we have significantly improved the ability to identify new alleles in unknown samples. Received: 12 August 1997 / Received in revised form: 7 November 1997