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Biomedical subjects

D O Taylor

Publications and source records attributed to D O Taylor.

At least 55 records · Page 3Linked to original sources
PubMed1993

Cyclophosphamide as an alternative to azathioprine in cardiac transplant recipients with suspected azathioprine-induced hepatotoxicity.

AZA has been reported to cause liver dysfunction in some recipients of solid organ transplants. To assess the safety and efficacy of cyclophosphamide in maintenance immunosuppression in the setting of AZA-induced liver dysfunction, we retrospectively reviewed the records of 320 surviving cardiac transplant recipients in Utah. Cyclophosphamide was substituted for AZA in 29 patients due to elevated liver enzymes. Patients were switched to cyclophosphamide 689 +/- 104 days after transplantation; total follow-up after initiation of cyclophosphamide was 540 +/- 56 days. The dose of cyclophosphamide after 2 and 6 months of cyclophosphamide therapy was 62 +/- 6 mg/day (0.8 +/- 0.1 mg/kg/day) and 48 +/- 5 mg/day (0.6 +/- 0.1 mg/kg/day), respectively, compared with 233 +/- 20 mg/day (2.9 +/- 0.2 mg/kg/day) of AZA. The substitution of cyclophosphamide for AZA was associated with a significant improvement in liver function tests. Liver enzymes decreased by up to 49% (P = 0.027), while serum bilirubin decreased by 58% (P < 0.001). Rejection frequency did not increase; neither corticosteroid nor CsA dosage was altered significantly after the substitution of cyclophosphamide. Significant bone marrow suppression was not observed; specifically, no significant change in white blood cell count or hematocrit occurred. Complications of treatment with cyclophosphamide were few; only 1 patient discontinued cyclophosphamide because of alopecia. We conclude that cyclophosphamide appears to be safe in maintenance immunosuppression, permitting the discontinuation of AZA in patients with AZA-induced hepatic dysfunction without necessitating the augmentation of either corticosteroids or CsA.

Alanine Transaminase↗
PubMed1993

Increased frequency of alloantigen-reactive helper T lymphocytes is associated with human cardiac allograft rejection.

Endomyocardial biopsy (EMB) is the standard method of monitoring heart transplant recipients for the development of allograft rejection. To date, noninvasive methods to detect cardiac allograft rejection have lacked adequate sensitivity and specificity for wide clinical application. In this study, limiting dilution analysis (LDA) was used to quantitate the number of donor alloantigen-reactive helper T lymphocytes (HTLs) in the peripheral blood of cardiac transplant recipients. Cadaveric donor splenocytes were cryopreserved, providing a source of donor alloantigenic stimulation for these assays. Peripheral blood mononuclear cells were harvested from cardiac transplant recipients before transplantation and at the time of EMB. LDA of donor-reactive HTLs was conducted simultaneously on all time points to minimize experimental variation, and these data were related to EMB scores. Frequencies of donor-reactive HTLs in pretransplant samples were highly variable, ranging from 1/1381 to < 1/200,000, and correlated poorly with the degree of HLA disparity. During episodes of moderate rejection, donor-specific HTL frequencies increased an average of 6 times their post-transplant baseline frequency. Additionally, 10-fold increases in HTL frequencies were seen preceding EMB-diagnosed rejection in several individuals. These data indicate that episodes of allograft rejection are associated with increases in the number of circulating donor-reactive HTL which are frequently detected before the development of histologically defined rejection. Thus, monitoring HTL frequencies may serve as a non-invasive method for detecting and predicting cardiac allograft rejection. Furthermore, this assay may provide a valuable means of assessing the in vivo efficacy of various immunosuppressive therapies.

Graft Rejection↗
PubMed1993

Pregnancy in heart transplant recipients: management and outcome.

OBJECTIVE: To determine the outcome of pregnancies in cardiac allograft recipients. METHODS: Thirty women who became pregnant after heart transplantation were identified from cases managed personally, questionnaires sent to all cardiac transplant centers, and review of the literature. Mothers were evaluated for evidence of rejection and for obstetric complications. The infants were observed for congenital abnormalities and perinatal morbidity or mortality. RESULTS: Frequent pregnancy complications included chronic hypertension (48%), preeclampsia (24%), and preterm labor (28%). The rate of cesarean delivery was 32%. Six episodes of rejection required treatment, and three late maternal deaths occurred. Among the 27 live births, 17 infants were born after 36 weeks' gestation and ten were preterm, five were small for gestational age, and four had neonatal complications. There were no congenital anomalies. CONCLUSION: Pregnancies in heart transplant recipients present management problems similar to those seen in patients with other allografts and should be considered high risk.

Adult↗
PubMed1992

Ventricle-to-brain ratio and symptoms at the onset of first-break schizophrenia.

Ventricle-to-brain ratio (VBR) was measured from the computed tomographic (CT) scans of 33 very recent-onset psychotic patients. Illness severity and positive and negative symptoms were also assessed in 21 of these patients with schizophreniform disorder. Forty-five neurology patients served as controls. Analyses revealed no significant differences between the VBR of the psychotic group as a whole, the schizophreniform subgroup, the affective psychotic subgroup, and the controls. Control subjects with a neurological diagnosis of vertigo or syncope had significantly higher VBR than the remainder of the control group and the psychotic group. When the psychotic group was compared to the control group minus those controls with syncope or vertigo, the psychotic group had significantly higher VBR. The schizophreniform subgroup also had significantly higher VBR than the control group minus subjects with vertigo or syncope. In the schizophreniform subgroup, positive symptoms and illness severity were associated with smaller VBR. There was no association between negative symptoms and VBR.

Adolescent↗
PubMed1985

Skin irritation testing in rabbits complicated by dermal mucormycosis.

Two insecticide formulations were evaluated for skin irritation using albino rabbits (Stauffland-White strain). While the active ingredient alone produced only mild skin irritation, corn grit formulation produced severe skin irritation. Corn grit from three sources (A, B, and C) was similarly evaluated for skin irritation and at 24 hr, all samples produced erythema and edema of both the abraded and nonabraded test sites. Eschar was observed in 72 hr in about half of the rabbits and persisted through termination on the 7th day. Histologic examination of skin specimens revealed that all three corn grit samples produced epidermatitis. In addition, rabbits exposed to corn grit from two sources (A and B), developed moderate focal to severe diffuse suppurative necrotizing folliculitis and dermatitis. Large tubular branching nonseptate hyphae compatible with the Mucorales species were seen in hair follicle micropustules of rabbits treated with corn grit from sources A and B. Mycologic culture techniques applied to corn grit from each source revealed a potential pathogen in the genus Rhizopus isolated from samples from sources A and C but not B. The skin irritation test involved application of test material covered with gauze to both abraded and nonabraded skin. Rubber damming was placed over the gauze and secured with tape. After 24-hr exposure all bandaging and visible test material were removed. Skin irritation was evaluated immediately after removal and then periodically until termination at 7 days.

Animals↗
PubMed1985

Inheritance of acquired changes in growth capacity of spontaneously transformed BALB/3T3 cells propagated in mice and in culture.

Five subclones were derived from a spontaneously transformed BALB/3T3 clone soon after its isolation. Despite their common clonal origin, the subclones were different from each other in appearance, colony-forming efficiency in agar (CFEag), and rate of tumor formation in mice. A comparison of growth properties during repeated passages in culture was made between the cells derived from the tumors and the cells used to initiate the tumors. In most cases, the tumor-derived cells had a much lower CFEag than did their parental in vitro-propagated cells, and the CFEag was restored slowly to the original level or remained at a reduced level during the period of study. In a few cases, the tumor-derived cells had almost as high a CFEag as their parental cells or were quickly restored to this level during cultivation. It was shown by karyotypic and clonal analysis that the reduced CFEag of the tumor-derived cells arose from a change in the transformed cells; i.e., it was not due to the presence of normal host cells in the explanted tumor. Clones of the tumor-derived cells tended to show the same patterns of change in CFEag as the uncloned tumor cell populations, but there were cases of individual variation in pattern among the tumor cell clones. Tumor cells with greatly reduced CFEag also grew a little more slowly on plastic than did the parental nontumor cells, and their growth rate tended to increase along with CFEag in long-term culture. Clonal analysis of one of the five original subclones failed to reveal cells which had the CFEag properties of its progeny tumor cells. This suggests that the reduction of CFEag during tumor formation arose by adaptation rather than selection of preexisting variants. A similar conclusion was drawn about the restoration of CFEag during cultivation of the tumor-derived cells. Although the decrease in CFEag which accompanied tumor formation varied in magnitude and stability, some tumor cell populations retained their reduced capacity through months of weekly passaging in culture, involving up to 100 cell divisions. The results are therefore consistent with the heretical notion of inheritance of acquired characteristics. In addition, the wide variation of in vitro growth capacity among tumors initiated by different subclones, and even among tumors initiated by the same subclone, raises the possibility that the complete chain of causality underlying the variation is intrinsically indeterminate.

Animals↗
PubMed1983

Lymphocyte migration in inbred Syrian hamsters with acute measles virus encephalitis.

The migratory pattern of 51Cr-labeled adult lymphocytes, as measured by 51Cr concentration in various tissues, was followed in inbred weanling Syrian hamsters infected intracranially with measles virus. Donor-labeled lymphocytes were inoculated intracardially into infected and control recipients. Increased passage of labeled lymphocytes across the blood-brain barrier was first seen on day 3 post virus inoculation and 1 day prior to development of clinical signs of acute measles encephalitis. 51Cr concentration in the brain increased progressively along with neurologic signs until the death of the hamsters. Aberration of lymphocyte migration peripherally, manifested by reduced presence of labeled cells in lymph nodes and spleen, first occurred 4 days post virus inoculation in those hamsters with clinical signs of disease. By days 5 and 6 post virus inoculation, the concentration of 51Cr in lymph nodes was 30% and 20%, respectively, of that in lymph nodes of control hamsters. Concentration of labeled lymphocytes in lymph nodes and spleen of the occasional virus-inoculated animal that appeared clinically well at time of autopsy was always greater than that in ill hamsters, and was closer to and sometimes equal to the concentration in the corresponding tissues of control hamsters. Thus, increased passage of labeled lymphocytes into the brain and decreased recovery of labeled lymphocytes in lymph nodes and spleen occurred concomitantly with increased neurologic signs of disease. No differences in presence of labeled cells in other tissues tested (liver, lung, thymus and blood) between infected and control hamsters were noted. Labeled lymphocytes from either measles virus or ovalbumin-immunized donors appeared to pass more readily into the brains of ill recipients than labeled lymphocytes from unimmunized donors.

Animals↗
PubMed1977

Complications and immunological studies of measles virus infection in antithymocyte-treated hamsters.

A study was done to investigate possible late central nervous system (CNS) complications of latent measles infection in hamsters. Signs of CNS disease, consisting of myoclonus and paralysis, occurred in some weanling hamsters inoculated intraperitoneally at 3 or 9 days of age with antithymocyte serum (ATS) and measles virus, but no late complications in adult life attributable to measles virus were seen. A single series of ATS injections plus an injection of measles virus resulted in sustained antibody formation postulated due to establishment of a latent viral infection, whereas similar treatment with normal rabbit serum plus virus caused no or minimal antibody response. The majority of hamsters receiving ATS as newborns and ATS plus virus as weanlings also did not produce antibody. This differential effect of ATS may be due to combined elimination of suppressor and helper cells in the latter ATS-treated group and of suppressor cells only in the former ATS-treated group. Cellular immunity could not be evaluated since lymphocytes from inoculated and uninoculated hamsters released equal and variable amounts of 51Cr for both infected and noninfected labeled, allogeneic hamster target cells.

Animals↗