Search PubMed⌕ Search

Biomedical subjects

C Paul

Publications and source records attributed to C Paul.

At least 235 records · Page 13Linked to original sources
PubMed1991

Myocardial toxicity of high-dose cyclophosphamide in rabbits treated with daunorubicin.

The present study was performed to evaluate experimentally the possible cardiotoxicity of high doses of cyclophosphamide after pretreatment with anthracyclines, a regimen used prior to bone marrow transplantation. A total of 27 rabbits received daunorubicin at a dose of 2.25 mg/kg per week for 10 weeks. At 1 week after the last daunorubicin dose, 13 of these rabbits received cyclophosphamide at 100 mg/kg per day x2 (total dose, 200 mg/kg). All animals were killed after 1 additional week. Seven rabbits received cyclophosphamide at 100 mg/kg per day x2 and two animals were given 50 mg/kg per day x2 without additional treatment. In all, 18 untreated rabbits served as controls. At 3 h before the animals were killed, they received [99mTc]-pyrophosphate i.v. Myocardial isotope activity was determined using a detector, and cardiac specimens were examined with a gamma-camera. Cardiotoxic effects were evaluated by myocardial isotope accumulation and pathologic changes were determined by morphology and by light and electron microscopy. The pathologic evaluation showed more frequent and widespread acute myocyte necrosis in daunorubicin/cyclophosphamide-treated rabbits as compared with those treated with daunorubicin or cyclophosphamide only. Myocardial isotope accumulation in rabbits treated with daunorubicin/cyclophosphamide was significantly higher then that in animals treated with either drug alone (2 alpha less than or equal to 0.001). Rabbits receiving cyclophosphamide as a single agent showed minor myocyte lesions but did not differ from controls in terms of isotope accumulation. We conclude that high-dose cyclophosphamide treatment on a dose schedule similar to that used prior to bone marrow transplantation and given soon after long-term daunorubicin therapy is considerably cardiotoxic.

Animals↗
PubMed1991

Intracellular uptake and cytotoxic effect in vitro of doxorubicin and epirubicin in human leukemic and normal hematopoietic cells.

Leukemic cells from patients presenting with acute nonlymphoblastic leukemia and normal hematopoietic bone marrow cells from healthy donors for allogeneic bone marrow transplantation were incubated for 3 h with doxorubicin and epirubicin at different concentrations. The intracellular uptake at the end of the incubation was determined by photofluorometry in leukemic cells from 15 patients and in normal cells from 9 donors for bone marrow transplantation. Cytotoxicity in vitro against granulocyte/macrophage colony-forming units (CFU-GM) was determined in normal cells from 7 donors, and in vitro toxicity against leukemic cells was determined by a clonogenic technique in cells from 6 patients and by vital dye staining (DiSC) following 4 days' culture in cells from 15 patients. Epirubicin was significantly less toxic than doxorubicin to normal hematopoetic cells (72% +/- 20% survival of cells for epirubicin vs 45% +/- 13% for doxorubicin at a concentration of 0.2 microM; P less than or equal to 0.005). As analyzed by the DiSC assay, 0.2 microM epirubicin was slightly more toxic to leukemic cells than was the same concentration of doxorubicin (47% vs 61% survival, P less than or equal to 0.01), but the clonogenic assay revealed no difference in toxicity to leukemic cells. At a concentration of 0.2 microM, the mean intracellular uptake of epirubicin in leukemic cells was 0.43 +/- 0.26 nmol/mg protein as compared with 0.33 +/- 0.14 nmol/mg protein for doxorubicin (not significant). In normal cells, the uptake of epirubicin at a concentration of 0.2 microM was 0.47 +/- 0.25 nmol/mg protein as compared with 0.31 +/- 0.21 nmol/mg protein for doxorubicin (not significant). The reduced myelotoxicity observed in vitro together with the retained toxicity to leukemic cells indicates that the therapeutic index of epirubicin is better than that of doxorubicin.

Bone Marrow Cells↗
PubMed1991

Chromoblastomycosis with malignant transformation and cutaneous-synovial secondary localization. The potential therapeutic role of itraconazole.

A case of neoplastic transformation of lesions of chromoblastomycosis is reported in a 67-year-old farmer from French Guyana. An interesting aspect of this case was the appearance of new cutaneous lesions of chromoblastomycosis, in a different site from the original lesion, and the presence of an infected synovial cyst. The potential therapeutic role of itraconazole is discussed.

Aged↗
PubMed1991

A feasibility study of organised cervical screening in southern New Zealand.

The 1985 electoral roll was used as a register to invite 1013 women to participate in a screening program. Appointment times and a choice of venues for having a smear were not provided. Overall, 26 per cent of the women sent invitations registered with the program. After adjustment for the prevalence of hysterectomy, the proportion who registered with the program was about 32 per cent. The low level of registration and difficulties experienced in tracing registrants and nonregistrants over time using the electoral roll resulted in the cessation of the program after 3 years. An assessment of the original invitation was made using a small case-control study, and associations between the screening history stated at interview and screening over the duration of the program were examined in nonregistrants.

Feasibility Studies↗
PubMed1991

Intravesical epirubicin with and without verapamil for the prophylaxis of superficial bladder tumours.

Seventy-five patients with recurrent bladder carcinoma were randomized after electroresection to receive either epirubicin (E) or epirubicin + verapamil (E + V) instillation of the bladder at regular intervals for 2 years. Samples of the bladder wall, tumour tissue and peripheral blood were taken from 20 patients. The average follow-up period was 21 months. Fifty per cent of the patients in the E group and 37% in the E + V group developed recurrent tumours. Recurrence rates (RR) were 6.3 and 4.7, respectively. Before the instillation therapy the RR was 16.0. There was a highly significant reduction of RR during the instillation therapies; in group E p less than 0.005 and in group E + V p less than 0.001. The difference between the treatment groups was not statistically significant. Verapamil increased epirubicin concentrations in both the bladder wall and the tumour tissue, but did not affect concentrations in the peripheral blood. Side effects were few and did not lead to discontinuation of treatment.

Administration, Intravesical↗
PubMed1991

Radiation dose rates from paediatric patients undergoing 99Tcm investigations.

Infants or children undergoing nuclear medicine investigations may subsequently come into close contact with nurses or parents responsible for their care. In order to estimate the radiation dose to these individuals, and to formulate appropriate recommendations, dose rates were measured at distances of 0.1, 0.5 and 1.0 m from 148 paediatric patients who had undergone one of 12 99Tcm studies. The maximum dose rates of 70, 14 and 5 microSv h-1 at these distances were not greater than the corresponding maximum values found in an earlier study of adult patients. However, the maximum dose rates per unit activity of 0.5, 0.2 and 0.1 microSv h-1 MBq-1 were greater than the corresponding maximum 99Tcm adult values, consistent with a general increase of dose rate per unit activity with decrease of body weight observed in the paediatric measurements. A parent caring for and feeding a young infant is most unlikely to receive a dose equivalent of 1 mSv, and a nurse attending to one young radioactive patient is most unlikely to receive a dose equivalent in a working day of 60 microSv. The data obtained should allow radiation doses to be estimated and appropriate recommendations to be formulated for other circumstances, including any future legislative changes in dose limits or derived levels.

Adolescent↗
PubMed1990

Oral contraceptives and risk of breast cancer.

A national population-based case-control study was conducted in New Zealand to assess the effects of hormonal contraception on breast-cancer risk. A total of 891 women aged 25 to 54 with a first diagnosis of breast cancer, and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk of breast cancer for women who had ever used oral contraceptives was 1.0 (95% confidence interval 0.82-1.3). There was no increase in risk with duration of use, even among women who had continued to use oral contraceptives for 14 or more years (relative risk = 1.1, 95% confidence interval 0.78-1.7). The risk of breast cancer was not increased by use of oral contraceptives for long periods before the first pregnancy or by starting use at a young age. Parity, age at menarche, family history of breast cancer, or history of benign breast disease did not modify the effect of oral contraceptives on breast-cancer risk. Relative risk estimates were slightly, although not significantly, increased during the first few years after starting oral contraception and in women under 35 years of age at diagnosis.

Adolescent↗
PubMed1990

Intracellular concentrations of anti cancer drugs in leukemic cells in vitro vs in vivo.

A comparison of intracellular concentrations of daunorubicin, doxorubicin and ara-C in myeloid blast cells was carried out in vivo and in vitro. In vivo, blood samples were obtained from 27 patients with acute nonlymphoblastic leukemia during and up to 4 days after drug infusion. Leukemic cells were isolated and drug concentrations were determined by HPLC. Before treatment, leukemic cells from 21 patients were isolated from blood and bone marrow, and in vitro incubations were done with anthracyclines for 1-3 h at concentrations of 0.1-1.0 microM and with ara-C for 1 h to 5 days at concentrations of 0.5-5.0 microM. The cells were cultured for 5 days, during which cell samples were taken for drug determination. The results showed that incubation with 0.2 microM daunorubicin for 1 h and 0.2 microM doxorubicin for 3 h and continuous exposure to 0.5 microM ara-C gave intracellular concentration curves similar to those obtained in vivo. After 5 days' culture, the cytotoxic effect was determined by vital dye staining with fast green, the addition of an internal standard of fixed goose erythrocytes, cytospin centrifugation and counter-staining of living cells with haematoxylin/eosin (DiSC). Incubations at the above-mentioned concentrations exerted a cytotoxic effect of approximately 50%. We conclude that in mimicking the in vivo situation, it is important to consider differences in intracellular pharmacokinetics.

Adult↗
PubMed1990

Uptake of low density lipoproteins by human leukemic cells in vivo: relation to plasma lipoprotein levels and possible relevance for selective chemotherapy.

The success of cancer chemotherapy is dependent on the possibility to utilize biological differences between malignant and normal cells to selectively destroy the tumor cells. One such difference may be that of receptor-mediated cellular uptake of low density lipoproteins (LDLs). Previous studies have shown that leukemic cells from patients with acute myelogenous leukemia have elevated receptor-mediated uptake and degradation rates of plasma LDL in vitro compared to normal white blood and bone marrow cells, and that plasma cholesterol levels at diagnosis are inversely correlated with the LDL receptor activity of the malignant cells. An important question is whether the uptake of LDL by the leukemic cells is also increased in vivo. To evaluate the in vivo uptake of LDL, 11 adult patients with newly diagnosed acute myelogenous leukemia received an i.v. injection of [14C]-sucrose-labeled LDL. On degradation of [14C]sucrose-LDL, the radiolabeled sucrose moiety is known to remain trapped in the lysosomal compartment of the cells. After injection, radioactivity accumulated progressively for at least 12 hr in the leukemic cells. The uptake of radioactivity in vivo correlated with the rate of receptor-mediated degradation of 125I-labeled LDL by the leukemic cells assayed in vitro (r = +0.88, P less than 0.001). An inverse correlation between plasma LDL cholesterol concentrations and the in vivo cellular uptake of [14C]sucrose-LDL in whole blood (r = -0.76, P less than 0.01) indicates that the hypocholesterolemia is due to elevated LDL uptake by the leukemic cells. Postmortem biopsies from virtually all tissues were obtained from one patient, and the distribution of radioactivity revealed that the liver and bone marrow had accumulated most radioactivity; the adrenals had the highest uptake of label per gram of tissue weight. The results indicate that LDL may be used as a carrier targeting lipophilic cytotoxic drugs to leukemic cells.

Adult↗
PubMed1990

The impact of unemployment insurance benefits on the probability of migration of the unemployed.

"By ignoring individual unemployment compensation benefits and conditions of job termination, past migration research has concluded that personal unemployment doubles the likelihood of interstate labor-force migration. Findings from the present study indicate that aggregating the unemployed, without adjusting for these two factors, overstates the probability of migration for the involuntarily unemployed benefit recipient and understates the likelihood of migration for the voluntarily unemployed benefit recipient. The results suggest that federal discretionary unemployment-compensation programs, which are implemented during recessionary periods, likely serve to retard out-migration of those who are involuntarily unemployed." Data are from a 1982 sample of unemployed U.S. workers.

Americas↗
PubMed1990

Evidence for diversity of Plasmodium falciparum sporozoite surface antigens derived from analysis of antibodies elicited in humans.

We have compared the reactivities of antibodies developed by individuals frequently exposed to Plasmodium falciparum infections with the epitopes contained within the repeats of the circumsporozoite (CS) protein and their reactivities with the epitopes of a native molecule(s) accessible on the sporozoite surface. Results of direct-binding assays and competition assays between artificial and native molecules or between human antibodies and anti-CS monoclonal antibodies suggest that humans respond preferentially to epitopes not contained within the repeats of the CS protein and probably not contained in the whole CS protein. Human monoclonal antibodies reactive with P. falciparum sporozoite surface antigens were produced by Epstein-Barr virus transformation of human lymphocytes. Their pattern of reactivity with sporozoites from a number of different isolates indicates the existence of several distinct epitopes on the parasite surface. Differences between isolates and between sporozoites within a given sample were observed. No single human monoclonal antibody capable of detecting an epitope expressed in all the parasites studied was found.

Animals↗
PubMed1990

[Divorces, 1989].

Explore the source record for details and available documents.

Adolescent↗
PubMed1990

Evaluation of an in vitro assay aimed at measuring protective antibodies against sporozoites.

We have evaluated the in vitro biological activities of antibodies directed against sporozoites and compared them with their capacity to protect against challenge with both human and rodent malaria. The anti-Plasmodium falciparum antibodies evaluated with the test included monoclonal antibodies (MAbs) NFS1 and NFS2 as well as polyclonal antibodies contained in human hyperimmune sera directed against sporozoites of P. falciparum. The inhibitory effect of these antibodies was dependent on their concentration. However, total inhibition was not observed except occasionally with highly concentrated MAbs (10-100 micrograms/ml). Strong but also incomplete inhibition was observed with sera from humans living in hyperendemic areas. In the P. yoelii rodent system, we tested sera from mice immunized with subunit vaccines. None of these mice were protected in vivo against challenge with 40-200 sporozoites. In vitro only a sub-total inhibition was achieved (maximum 91% at 1:10 serum dilution). In contrast, we tested sera from mice that received NYS1, an IgG3 MAb, in passive transfer and were protected against challenge with 5000 sporozoites. At 1:10 dilution, 100% inhibition was achieved in vitro while IFA titres from these mice were similar to those of vaccinated mice. These data show a close correlation between in vivo and in vitro findings and thus suggest that the inhibition of liver-stage development assay (ILSDA) appears appropriate to evaluate the potential of antibodies.

Adult↗