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Biomedical subjects

C Paul

Publications and source records attributed to C Paul.

At least 253 records · Page 14Linked to original sources
PubMed1990

[Representative epidemiologic study of influence factors on the periodontal loss of attachment].

The influence of age, inflammation intensity, tooth surface quality (caries, fillings), as well as mucogingival conditions on the loss of attachment was examined in 2000 probands. The loss of attachment was subdivided into periodontal pocket-formation and recessions. Determining cause is not the age but the inflammatory degree even if there is a significant increase of the attachment loss from age group to age group. The main part of the attachment loss increasing with advancing age is caused by recession development. Then, the individual dispersion is very high. Incorrect restorations, caries but also correct fillings increase periodontal disease. Mucogingival conditions show importance only in extreme case. There are less inflammations with pocket-formation than recessions. A preventive oriented basic care of the population is necessary to reduce irreversible damages of the periodontium.

Adolescent↗
PubMed1989

Depot medroxyprogesterone (Depo-Provera) and risk of breast cancer.

OBJECTIVE: To determine whether use of the injectable contraceptive depot medroxyprogesterone acetate (Depo-Provera) affects the risk of breast cancer in women. DESIGN: A population based case-control study. SETTING: Nationwide community study. SUBJECTS: 891 Women aged 25-54 with newly diagnosed breast cancer were compared with 1864 women selected at random from the electoral rolls. INTERVENTION: Women were interviewed by telephone about past use of contraceptives and about possible risk factors for breast cancer. MAIN OUTCOME MEASURE: Relative risk of breast cancer in women who had used medroxyprogesterone. RESULTS: Medroxyprogesterone had been used by 110 patients and 252 controls. Overall, the relative risk of breast cancer associated with any duration of use was 1.0 (95% confidence interval 0.80 to 1.3). In women aged 25-34 the relative risk was 2.0 (1.0 to 3.8). The relative risk was highest in women aged 25-34 who had used the drug for six years or longer, although there were few women in this category. Women who had used it for two years or longer before age 25 had an increased risk of breast cancer (relative risk 4.6; 1.4 to 15.1). CONCLUSION: Despite the lack of an overall association these findings suggest that medroxyprogesterone may increase the risk of breast cancer in young women.

Adult↗
PubMed1989

Comparison of the intracellular pharmacokinetics of doxorubicin and 4'-epi-doxorubicin in patients with acute leukemia.

A direct comparison of the intracellular pharmacokinetics of 4'-epi-doxorubicin and doxorubicin was carried out in five patients with leukemia who were given weekly low doses of a combination of these drugs at 20 mg each in an i.v. injection. Blood samples were collected for 48 h after administration and the drug concentrations in leukemic cells were determined by high-performance liquid chromatography (HPLC). The intracellular peak concentrations of 4'-epi-doxorubicin were higher than those of doxorubicin in all patients. The AUC for the intracellular drug concentration vs time curve was significantly higher for 4'-epi-doxorubicin. The intracellular uptake and retention were also studied in vitro after incubation of isolated leukemic blast cells with the two drugs; they showed the same pattern observed in vivo. We conclude that 4'-epi-doxorubicin and doxorubicin exhibit different pharmacokinetics in malignant cells. The therapeutic significance of this finding requires further evaluation.

Acute Disease↗
PubMed1989

Increasing the accumulation of daunorubicin in human leukemic cells by prolonging the infusion time.

Eight patients with acute nonlymphoblastic leukemia were treated with a combination of daunorubicin (1.5 mg/kg body weight) and cytosine arabinoside. The infusion time of daunorubicin was varied from 10 min to 24 h. One patient received the drug during 24 h in one treatment course and during 10 min in the subsequent course. The concentrations of daunorubicin and its main metabolite, daunorubicinol, were monitored simultaneously in plasma and in leukemic cells using high performance liquid chromatography. Infusion during 24 h gave a peak plasma concentration of daunorubicin that was less than one tenth of that observed after infusion for 10 min, while the areas under the plasma concentration vs time curves were similar. In contrast, prolonging the infusion time increased the area under the cellular concentration vs time curve from a mean of 3.3 nmol x h/mg cell protein for infusions less than one hour to 13.7 and 17.0 nmol x h/mg cell protein in two patients who received the same dose as a 24-h infusion. The duration of the infusion did not influence the intracellular levels of daunorubicinol. We conclude that the infusion times appear to affect the concentration of daunorubicin in the leukemic cells and may be important for the therapeutic effects of daunorubicin.

Cell Transformation, Neoplastic↗
PubMed1989

Pharmacokinetics of daunorubicin and doxorubicin in plasma and leukemic cells from patients with acute nonlymphoblastic leukemia.

The pharmacokinetics of daunorubicin and doxorubicin were studied in plasma and leukemic cells from 16 patients with acute nonlymphoblastic leukemia during 19 courses of treatment with the unconjugated or DNA-conjugated drugs. Daunorubicin and doxorubicin are high-clearance drugs with very high apparent volumes of distribution, indicating a pronounced tissue affinity. This was more pronounced in the case of doxorubicin and may explain the reduced cardiotoxicity of the DNA-complexes. Daunorubicin reached higher intracellular peak concentrations than doxorubicin, but the latter drug was retained much longer. The cell/plasma concentration ratio was higher for daunorubicin than for its reduced metabolite daunorubicinol. No doxorubicinol was found intracellularly. The observed differences in cellular pharmacokinetics between daunorubicin and doxorubicin may explain the difference between the clinical activity spectras of these two drugs. DNA-conjugation did not markedly modify the uptake of daunorubicin in the leukemic cells, whereas the mean intracellular accumulation of doxorubicin was 60% higher when the drug was administered as a DNA-conjugate. This may enhance the selectivity of doxorubicin in the treatment of acute leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

In vitro drug testing in patients with acute leukemia with incubations mimicking in vivo intracellular drug concentrations.

The differential staining cytotoxicity (DiSC) assay was evaluated as a predictive test for response to therapy in patients with acute non-lymphoblastic leukemia. Incubations were designed in such a way that the intracellular concentrations of cytostatic drugs in vitro paralleled those in vivo. Leukemic cells were isolated from 53 patients with acute non-lymphocytic leukemia. 13 of these patients died early due to supportive care failure and were not evaluable for the predictive drug testing. Of the remaining 40 patients, 25 entered a complete remission (CR) and 15 had a resistant disease (RD). According to the patients randomization to therapy the cells were incubated with anthracyclines and Ara-C separately and in combination. After 4 days of culturing in liquid medium the in vitro cytotoxicity was determined by dye exclusion according to Weisenthal. The cytotoxic effect in vitro was significantly higher on cells from patients who achieved a CR compared to patients with RD after incubations with anthracyclines 0.2 mumol/l (p less than or equal to 0.005), Ara-C 0.5 mumol/l (p less than or equal to 0.05) and with the combination of anthracyclines with Ara-C (p less than or equal to 0.0005). The best predictive value was achieved when incubations with 0.2 mumol/l anthracyclines and 0.5 mumol/l Ara-C were analyzed together. With these incubations cells from 20 out of 21 patients who achieved CR showed either less than or equal to 60% surviving cells after the anthracycline incubation or less than or equal to 35% surviving cells after the Ara-C incubation. Cells from 11 out of 13 patients with RD did not fulfill either of these criteria. In vitro drug sensitivity was significantly correlated to a prolonged survival (p less than 0.01). We conclude that, when performed with incubations that mimic in vivo tumor cell exposure to cytostatic drugs, the DiSC assay shows a high correlation to clinical outcome for patients with acute non-lymphocytic leukemia.

Adolescent↗
PubMed1989

The influence of experimental conditions on the spectrin-hemoglobin interaction.

Human spectrin, when isolated, purified and stored in such conditions that preserve its tetrameric form, is able to associate with human hemoglobin as it is clearly shown by gel filtration. However, this hemoglobin-spectrin association does not seem to have a significant effect on hemoglobin oxygenation as indicated by equilibrium and rapid kinetics measurements.

Adhesiveness↗
PubMed1988

Contraceptive practice in New Zealand.

A survey of contraceptive practice in New Zealand was carried out using a population-based sample of women, aged 25 to 54, selected as control subjects in a national case-control study. The results showed that sterilisation has become the most common means of family limitation. Overall, 45% of women aged 25 to 54 were in a union where one or the other partner had been sterilised. Vasectomy was the most common method of contraceptive sterilisation. The frequency of hysterectomy contributed to the high rates of sterilisation; 12% of women had had a hysterectomy. Over 80% of New Zealand women had used an oral contraceptive at some time, but only 11% were using the pill at the time of the survey. Comparison with earlier studies of contraceptive use in New Zealand show there has been a marked increase in the prevalence of contraceptive sterilisation, and a marked decrease in the use of oral contraceptives.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Mammographic screening for breast cancer: prospects for New Zealand.

The Cancer Society and the Department of Health invited a working group to make recommendations on screening by mammography. Mammography offers the best opportunity for preventing deaths from breast cancer. Randomised trials suggest that mortality can be reduced by about 30% in women over 50; the value of routine mammography in younger women is still uncertain. Apart from financial costs, the main drawback of mammography is that many women receive unnecessary investigation because of false-positive results. Careful design and monitoring of programmes is essential to ensure that the benefits of screening outweigh the disadvantages. In New Zealand there is a shortage of radiologists, pathologists, and clinicians who are skilled in the specialised techniques required for the screening of asymptomatic women. Decisions about routine screening should be delayed until pilot programmes have been established, with assessment of their effectiveness, economic efficiency, and social acceptability. Recommendations for the design of such programmes are made.

Adult↗
PubMed1988

Localisation of satellite DNA sequences on human metaphase chromosomes using bromodeoxyuridine-labelled probes.

Human highly repeated satellite sequences, cloned into M13, were used as templates to prepare single-stranded DNA probes containing bromodeoxyuridine (BrdUrd) in place of thymine. The probes were hybridised to human metaphase chromosomes and visualised using an indirect immunological detection procedure. The sensitivity and accuracy of the technique were tested using a BrdUrd-labelled probe of known copy number and location: a segment from the 2.5 kb Y chromosome repeat. The procedure proved to be reliable and fast, with a sensitivity similar to that of other in situ hybridisation techniques. The technique was then used to determine the chromosomal locations of a 100 bp repeat from human satellite 3. The satellite 3 probe hybridised to a large number of chromosomes and, surprisingly, the intensity of label at all locations remained unchanged when the slides were washed at a higher stringency. The resolution of the technique was very high and allowed accurate localisation of the satellite sequence. Hybridisation was observed in two regions of the subcentromeric heterochromatin of chromosome 9, in two locations at the centromere and short arm of all the acrocentric autosomes, and at the centromere and long arm of the Y chromosome. In addition the probe hybridised to centromeric heterochromatin in chromosomes 1, 16, 17 and 20. We believe that single-stranded BrdUrd-labelled probes should be very useful for detecting RNA transcripts in cells, and discuss ways by which the procedure could be modified to locate single copy DNA on chromosomes.

Base Sequence↗
PubMed1988

Effects of verapamil on uptake and in vitro toxicity of anthracyclines in human leukemic blast cells.

The effect of a calcium channel blocker, verapamil, on intracellular uptake and cytotoxicity of anthracyclines in vitro was studied on leukemic cells from 32 patients with acute non-lymphoblastic leukemia. Cells were isolated from peripheral blood or bone-marrow and incubated with a concentration of 0.2 mumol/l, 0.5 mumol/l and/or 1.0 mumol/l of doxorubicin or daunorubicin in the absence and presence of verapamil at a concentration of 2 mumol/l and/or 10 mumol/l. Intracellular uptake was determined at the end of the incubations by photofluorometer and the in vitro cytotoxicity was determined after 5 days culturing in liquid medium by dye exclusion according to Weisenthal. Verapamil significantly increased the intracellular uptake of anthracyclines 0.5 mumol/l and 1.0 mumol/l and the cytotoxic effect of anthracyclines 0.2 mumol/l and 0.5 mumol/l and affected doxorubicin and daunorubicin equally. There were no significant differences between the two concentrations of verapamil. Cells from different FAB-groups were equally affected by verapamil. The effect on intracellular uptake was higher in cells from patients who were resistant to therapy compared to those who achieved a complete remission. We conclude that verapamil has an effect on intracellular uptake and cytotoxicity of anthracyclines on tumor cells from patients with acute non-lymphoblastic leukemia. The prognostic and therapeutic relevance of this has to be further evaluated.

Acute Disease↗
PubMed1986

Oral contraceptives and breast cancer: a national study.

In a population based case-control study 433 New Zealand women aged 25-54 with newly diagnosed breast cancer were compared with 897 women selected at random from the electoral rolls. The relative risk of breast cancer in women who had ever used oral contraceptives was 0.94 (95% confidence interval 0.70 to 1.25). The relative risk in women aged 25-34 at diagnosis was estimated to be 2.2 (95% confidence interval 0.47 to 9.9) and in older women less than 1. Analyses of risk by duration of use of oral contraceptives, age at first use, and time since first use showed no adverse effect of the pill. In particular, there was no increased risk in women who had used oral contraceptives before the age of 25 or before their first pregnancy, even for prolonged periods. Given the high prevalence of use in New Zealand, this study provides strong evidence against the hypothesis that use of oral contraceptives at young ages increases the risk of breast cancer.

Adult↗