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T Duffy

Publications and source records attributed to T Duffy.

At least 37 records · Page 2Linked to original sources
PubMed1989

Aluminum induced anemia: pathogenesis and treatment in patients on chronic hemodialysis.

The baseline hematologic status of 27 patients with modest degrees of aluminum overload was examined. In addition, hematologic data were evaluated in 19 of these patients during and after treatment with DFO. Although neither severe anemia nor microcytosis was observed pretreatment, there was a significant correlation between hemoglobin level and degree of aluminum burden as determined by bone surface aluminum staining (r = -0.58; P less than 0.007). Following treatment with DFO, hemoglobin concentration increased dramatically by 1.3 to 4.4 g/dl in eight patients but did not change in the remaining eleven. Responders and nonresponders were similar with regard to the degree of aluminum overload both before and after chelation therapy but differed with regard to baseline levels of erythropoietin (higher in responders) and degree of iron overload (greater in nonresponders). Pretherapy levels of red cell ALA dehydratase were depressed in all patients (32 +/- 4 vs. 56 +/- 5 U/g Hb in normals) but did not correlate with the degree of aluminum overload and did not change with chelation therapy. Pretherapy levels of red cell protoporphyrin were elevated in 15 of 24 patients (62%) and were higher in responders than in nonresponders. Following DFO therapy, levels fell by 25 to 50% in 7 of 8 patients with elevated pretherapy values, despite the tendency in several patients to develop iron deficiency with treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1989

Clinical significance, prevalence, and natural history of thrombocytopenia in pregnancy-induced hypertension.

The purpose of this study was to establish the prevalence and clinical significance of thrombocytopenia in pregnancy-induced hypertension (PIH). Thrombocytopenia, defined as a platelet count less than 100,000/mm3 was found in 11.6% of all patients with PIH. Logistic regression analysis was used to assess the relative contribution of thrombocytopenia, proteinuria, and the degree of hypertension to maternal and perinatal outcome. Thrombocytopenia was the principal contributor to the occurrence of abdominal pain, liver dysfunction, the presence of schistocytes in the peripheral smear, proteinuria, fetal distress, and the requirement for blood transfusions. Thrombocytopenia was also associated with a higher incidence of preterm delivery and intrauterine growth retardation. The nadir platelet count occurred within 48 hours of delivery in 56.7% (21 of 37) of cases. The median number of days for recovery of the thrombocytopenia was 2.0 days (range, 0 to 8 days). In five patients thrombocytopenia preceded the clinical manifestations of PIH. We conclude that thrombocytopenia is an independent and important risk factor for the occurrence of maternal and perinatal complications in PIH.

Abdomen↗
PubMed1988

Fibrinopeptide A during normal pregnancy.

Fibrinopeptide A (FPA) is the first peptide released from fibrinogen upon thrombin action. Plasma FPA is cleared rapidly with a first order kinetics and therefore its level reflects the rate of thrombin cleavage of fibrinogen. A prospective study was undertaken to establish normal values of FPA during pregnancy. The mean FPA for the pregnant group (n = 136) was 2.8 ng/ml (SD = 3.3) while it was 1.24 ng/ml (SD = 0.4) for a nonpregnant control group of healthy women (n = 30). The median FPA for the pregnant group was 2.2 ng/ml and 1.4 ng/ml for the nonpregnant group (Wilcoxon test P less than 0.0001). Plasma FPA levels increased with gestational age. The median value was 1.5 ng/ml in the first trimester (n = 18), 1.8 ng/ml in the second trimester (n = 40), and 2.5 ng/ml in the third trimester (n = 78). Plasma FPA concentrations in the third trimester were significantly higher than in the first and second trimester. These findings suggest increased thrombin activity and fibrin generation during the course of normal pregnancy.

Cross-Sectional Studies↗
PubMed1988

Clinical significance of liver dysfunction in pregnancy-induced hypertension.

Hepatic dysfunction is one of the frequent manifestations of multisystemic involvement in preeclampsia. This study was conducted to establish the impact of liver dysfunction on maternal and neonatal outcome in women with pregnancy-induced hypertension (PIH). The prevalence of liver dysfunction as determined by an elevated serum glutamic oxalacetic transaminase (SGOT) concentration was 21% in a population of 355 patients with PIH. Liver dysfunction was associated with the presence of severe hypertension, proteinuria, a lower platelet count, and renal compromise (elevated blood urea nitrogen, creatinine, and uric acid serum concentrations). Abdominal pain was also associated with an SGOT elevation. Liver dysfunction was associated with intrauterine growth retardation and prematurity. Furthermore, the association with these neonatal complications was independent from the severity of the hypertension and the presence of proteinuria. Thus, we conclude that liver dysfunction is a frequent complication of PIH and that it is an independent risk factor for maternal and perinatal complications.

Aspartate Aminotransferases↗
PubMed1987

Platinum-folate compounds: synthesis, properties and biological activity.

Cis-diamminediaquaplatinum(II)-ion, the biologically active form of the anticancer agent Cisplatin, reacted readily with tetrahydrofolate at pH 7 and 37 degrees C to produce a stable complex. The reaction was monitored spectrophotometrically by the change in absorbance maximum from 298 nm (tetrahydrofolate) to 275 nm (complex); occurrence of isobestic points at 282 and 327 nm indicated that a single product was formed. Purity of platinum-tetrahydrofolate, after isolation in ca. 70% yield, was established by TLC and HPLC. Elemental analysis, absorbance spectra at various pH values and nmr spectra provided evidence that the diammine platinum moiety was bridged across the N-5 and N-10 positions of tetrahydrofolate. Complexation also occurred with 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, Methotrexate and aminopterin, but not with folate or 7,8-dihydrofolate. Biological implications of these observations have been investigated. Intracellular folates in L1210 cells have been identified and quantitated via reverse phase HPLC (C18 column; tetrabutylammonium phosphate as the pairing ion) and changes in the levels of these compounds, after exposure of cells to Cisplatin, have been measured. Platinum derivatives of tetrahydrofolate or other reduced folates were not found, but there was a decrease in the level of 5,10-methenyltetrahydrofolate, accompanied by an increase in 5-formyl and 10-formyltetrahydrofolate (and perhaps tetrahydrofolate). The chemical interaction of the diaqua form of Cisplatin with Methotrexate resulted in decreased uptake of the latter by L1210 cells. The platinum complex of tetrahydrofolate was a reasonably good inhibitor (Ki = 4 microM) of L1210 dihydrofolate reductase and of the folate transport system (50% inhibition at ca. 200 microM) of L1210 cells.

Animals↗
PubMed1985

Acne urticata associated with chronic myelogenous leukemia.

A 56-year-old woman presented with a 6-month history of acne urticata, an intensely pruritic papulopustular eruption. Skin biopsy was nondiagnostic. Touch preparations of individual lesions were remarkable for numerous eosinophils. Peripheral blood count, bone marrow examination, and Philadelphia chromosome positivity confirmed a diagnosis of chronic myelogenous leukemia. A serum histamine level was markedly elevated. Treatment with hydroxyurea and antihistamines led to resolution of the skin eruption and improvement of the pruritus.

Acne Vulgaris↗
PubMed1985

The immunological basis of tumor rejection: the absolute dependence of the effector arm on sensitized T cells after chemoimmunotherapy of a murine sarcoma.

The mechanisms of tumor rejection were investigated by using a therapeutic model system involving treatment of C57BL/6J (B6) mice bearing the syngeneic MCA/76-9 or the unrelated MCA/76-64 sarcomas with cytoxan and tumor-sensitized T lymphocytes. Separated tumor-associated T lymphocytes (TAL) and tumor-associated macrophages (TAM) isolated from the regressing tumors 8 to 10 days after combination therapy expressed relatively specific cytotoxicity in vitro, whereas the unseparated tumor-associated cells (TAC), consisting of a mixture of TAL and TAM, expressed nonspecific cytotoxicity. TAM-mediated cytotoxicity was not dependent on the presence of TAL, as shown by T cell depletion of TAM or TAC cultures with the use of monoclonal anti-Thy-1 or anti-Lyt-2 antibody and complement. In contrast, the nonspecific cytotoxicity was dependent on the presence of T cells. In vivo assays using the Winn test failed to confirm certain aspects of the in vitro data. Without exception, the TAC inhibited tumor growth in an immunologically specific manner, having no effect on the growth of the unrelated B6 sarcoma. T cell depletion completely abrogated in vivo cytotoxicity. Specificity of tumor growth inhibition was confirmed in a bystander experiment in which TAC were mixed with both tumor cell types and were injected into recipient B6 mice. Tumors grew under these conditions, but the tumor that grew consisted only of those tumor cells toward which TAC cytotoxicity was not specifically directed. A bioassay indicated that the specifically immune antitumor effects at the site of regression were initiated between days 3 and 7 after combination therapy. By days 7 and 9, few tumorigenic stem cells could be detected at the tumor site. However, T cell depletion of the TAC isolated on days 8 to 10 resulted in enhanced tumor growth when the depleted TAC were injected into recipient mice. The conclusions reached were that tumor rejection was absolutely dependent on T cell participation at the tumor site, and that if TAM were involved, they required the presence of TAL and did not express nonspecific antitumor cytotoxicity. Indeed, the accelerated tumor growth seen in the absence of TAL suggested the possibility that TAM were growth stimulatory.

Animals↗
PubMed1984

Tumor-associated macrophages stimulate the proliferation of murine tumor cells surviving treatment with the oncolytic cyclophosphamide analogue Asta Z-7557: in vivo implications.

This report is concerned with the hypothesis that tumor-associated macrophages (TAM) present during cyclophosphamide (CY)-induced tumor regression stimulate proliferation of tumor stem cells that remain after the oncolytic after of CY has dissipated. In preliminary studies, plasma or serum from CY-injected mice was used as a source of CY metabolites. However, because of the relatively high background toxicity of normal mouse plasma/serum and the lack of a precise technique to quantify how much metabolite was present at any one time, this approach was abandoned. In place of the plasma metabolites, we used the Cy analogue, 4-(2-sulfonatoethylthio)-cyclophosphamide cyclohexylamine salt, Asta Z-7557. On solubilization in water, Asta Z-7557 yields phosphoramide mustard, one of the oncolytic metabolites of CY in vivo. This approach enabled us to quantitate the amount of drug used in vitro and to control the amount to which tumor cells and macrophages were exposed. It was demonstrated that when two different C57BL/6J tumor cell targets, the MCA/76-9 sarcoma and the EL4 lymphoma subline, E2G.2, were treated with defined quantities of Asta Z-7557, those cells surviving the toxic effects were stimulated to proliferate in the presence of TAM isolated from the MCA/76-9 sarcoma. Although pretreatment of the TAM with the drug slightly diminished the stimulatory effect, this was still significantly greater than the effect of culture medium alone. In no instance was there evidence that drug treatment rendered the macrophages cytotoxic towards the tumor cells. The data supported the notion that in vivo the presence of a high proportion of TAM during CY-induced temporary tumor regression may contribute directly to the resurgence of tumor growth.

Animals↗
PubMed1984

Resistance to methotrexate due to gene amplification in a patient with acute leukemia.

A patient is described with acute myelocytic leukemia refractory to conventional therapy, who also became highly resistant to methotrexate (MTX) after repeated courses of this drug. Leukemia cells from this patient were found to contain an elevated level of dihydrofolate reductase (DHFR) activity, with no change in the affinity of the enzyme for MTX. A sensitive "dot blot" assay revealed a fourfold increase in the gene copy number of DHFR. Southern blot analysis with a human DHFR cDNA probe confirmed this increase in the gene copy number, and demonstrated a similar restriction pattern with Eco R1, Hind III, and Pst 1 as seen with a highly amplified human leukemia cell line, K562. Additional DHFR fragments were detected, not seen in the K562 blot, suggesting the presence of pseudogenes, or a result of gene rearrangements occurring as part of the amplification process. Resistance to MTX in this patient was therefore ascribed to gene amplification and overproduction of DHFR.

Adult↗
PubMed1984

Enzyme immunoassay for pregnancy-associated plasma protein-A.

This enzyme immunoassay procedure for pregnancy-associated plasma protein type A involves a "sandwich"-type system in microtitration plates. One can detect 0.27 mg of the protein per liter of serum, with a between-batch CV of 10.2%, and the antiserum used does not cross react with any of the other placentally derived proteins. A reference interval for the last trimester of pregnancy is presented. The procedure described is suitable for studying the behavior of this protein during pregnancy.

Cross Reactions↗
PubMed1979

Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography.

We measured cardiac performance sequentially, using quantitative radionuclide angiocardiography to estimate left ventricular ejection fraction in 55 patients receiving doxorubicin for treatment of cancer. With final doxorubicin dosages greater than 350 mg per square meter, the lowest ejection fraction measured was significantly less than the initial determination. Five patients had severe cardiotoxicity (congestive heart failure). All had an ejection fraction of less than 30 per cent at the time of heart failure, and demonstrated moderate cardiotoxicity (a decline in ejection fraction by at least 15 per cent to a final value of less than 45 per cent) before clinical manifestations. Six patients with moderate toxicity in whom doxorubicin was discontinued did not have heart failure or a further decline in ejection fraction during the follow-up period. Moderate toxicity was continued, but mild toxicity (decline of ejection fraction by greater than 10 per cent, noted in 11 patients) was not well predicted. The assessment of radionuclide left ventricular ejection fraction during doxorubicin therapy may make it possible to avoid congestive heart failure.

Adult↗
PubMed1979

Flexible sigmoidoscopy as a screening procedure for neoplasia of the colon.

Two hundred asymptomatic United States veterans older than 40 years of age were evaluated with a flexible sigmoidoscope plus Hemoccult stool tests. Mean distance and time for the former were 56.4 centimeters and 7.4 minutes, respectively. There were no complications. Polyps greater than or equal to 0.5 centimeter in diameter were found in 11.9 per cent of those older than 50 years. No polyps of this size were found in patients younger than 50 year of age. Results of Hemoccult tests were negative in 83.3 per cent of those with polyps. A flexible sigmoidoscope is a safe, rapid and effective means of identifying that portion of the asymptomatic adult population having colonic polyps. For this purpose, it is vastly more sensitive than Hemoccult stool testing. Because of the relationship between colonic polyps and carcinoma, this technique may prove invaluable in the identification of those patients with an increased potential for the development of carcinoma of the colon.

Adult↗
PubMed1977

Sonography in the diagnosis of retroperitoneal fibrosis.

The ultrasonic appearance of retroperitoneal fibrosis is characteristic: a smooth-bordered and relatively echo-free mass anterior to the sacral promontory. Sonography can be used to confirm the diagnosis, follow response to therapy and detect hydronephrotic changes in the kidneys.

Adult↗