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Biomedical subjects

C Paul

Publications and source records attributed to C Paul.

At least 19 recordsLinked to original sources
PubMed1995

Quantitative determination of polyethylene glycol based upon its salting out and partitioning of a dye into the resulting aqueous two-phase system.

A method is described that allows quantitative determination of polyethylene glycol (PEG) concentrations by spectrophotometric measurement of fluorescein dye absorbance after its partitioning into an aqueous two-phase system containing mPEG (M(r) 5 kDa) in the upper phase and ammonium sulfate in the lower phase. The absorbance decrease of fluorescein in the lower phase is directly proportional to the mPEG concentration, with two proportionality constants equal to 4.42 x 10(5) and 2.84 x 10(5) M-1 cm-1 in the range of 0-0.4 and 0.4-1 microM, respectively. This experimental technique can be extended to PEGs of other molecular weights by means of calibration curves that give for each size of PEG the adequate proportionality constants. The results indicate that the quantitative determination is not affected by the presence of many substances such as proteins, reducing agents, and salts, at the usual concentrations.

Coloring Agents↗
PubMed1995

Characterization of an anthracycline-resistant human promyelocyte leukemia (HL-60) cell line with an elevated MDR-1 gene expression.

Multidrug resistance to a variety of cytotoxic drugs is due to decreased drug accumulation at the intracellular site of drug action. When due to increased energy-dependent drug efflux, this transport change is often associated with increased expression of an efflux pump for various lipophilic compounds, for example the P-glycoprotein which is the product of the MDR-1 gene. However, previously described HL-60 human promyelocytic leukemia cell lines resistant to the cytotoxic effect of anthracyclines have been reported not to express P-glycoprotein. We have isolated, by drug selection, an anthracycline-resistant HL-60 cell line that, in comparison to parental drug sensitive cells, exhibits a multidrug resistant phenotype including diminished intracellular drug retention, cross-resistance to multiple cytotoxic drugs, increased expression of a monoclonal antibody C219-reactive 180 kDa P-glycoprotein detected by Western blot analysis as well as increased expression of MDR-1 mRNA as determined by Northern blot and solution hybridization/RNAse protection analyses. Evidence is presented that the anthracycline-resistant HL-60 cells have amplified the MDR-1 gene.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Depot medroxyprogesterone acetate and breast cancer. A pooled analysis of the World Health Organization and New Zealand studies.

BACKGROUND: Although depot medroxyprogesterone acetate (DMPA) (Depo-Provera) has now been approved for marketing as a contraceptive in the United States, there are still unresolved issues about the relation between DMPA and risk of breast cancer. The two substantial case-control studies of this association yielded similar but inconclusive results. Because their designs were compatible, these studies were pooled to obtain more adequate data for analysis. DESIGN: Pooled results from two case-control studies. SETTING: New Zealand (entire country), Thailand (three centers), Mexico (one center), and Kenya (one center). PARTICIPANTS: A total of 1768 women with breast cancer and 13,905 controls, most of whom were younger than 55 years. MAIN OUTCOME MEASURE: Relative risk (RR) of breast cancer in women who had used DMPA. RESULTS: The RR of breast cancer for women who had ever used DMPA was 1.1 (95% confidence interval [CI], 0.97 to 1.4). There was no increase in risk with increasing duration of use of DMPA, but RR estimates were higher in certain subgroups of women. Further analyses suggested that recent (or current) use was the key factor, with women who had started using DMPA within the previous 5 years estimated to have an RR of 2.0 (95% CI, 1.5 to 2.8). CONCLUSIONS: The increased risk of breast cancer observed in recent (or current) users could be due to enhanced detection of breast tumors in women using DMPA or to acceleration of the growth of preexisting tumors. Women who had used DMPA more than 5 years previously had no increase in risk of breast cancer, regardless of their duration of use.

Adolescent↗
PubMed1995

Alpha-2a interferon therapy and antibody formation in patients with essential thrombocythemia and polycythemia vera with thrombocytosis.

In ten patients with essential thrombocythemia and polycythemia vera with thrombocytosis we have investigated the therapeutic effect of recombinant alpha-2a interferon (Roceron-A) given subcutaneously in a maintenance dosage of 3 million units three times weekly. The aim was to normalize the platelet count (< or = 400 x 10(9)/L). One of the secondary aims was to study platelet activity measured as beta-thromboglobulin (beta-TG) in urine. All but one patient could administer the injections and in all patients a significant reduction in platelet values was seen. The treatment was discontinued in three patients due to side effects of interferon, two because of hair loss (one with irreversible alopecia), and one because of depression. Three patients developed antibodies to alpha-2a interferon and a concomitant rise in the platelet level; in one patient therapy was switched to leukocyte alpha-interferon with an excellent response. The initial levels of beta-TG were elevated in 9/10 patients and were significantly reduced at 6 months in 4/5 patients not developing antibodies. Six patients are still on alpha-interferon therapy with a long-term follow-up of 3-3.5 years. We conclude that alpha-interferon therapy may be an alternative in patients with thrombocytosis and/or complications necessitating treatment.

Antibody Formation↗
PubMed1995

Postprandial gallbladder motor function: refilling and turnover of bile in health and in cholelithiasis.

BACKGROUND & AIMS: Impaired gallbladder emptying is implicated in gallstone disease. Ultrasonography and scintigraphy have shown conflicting results because the former is influenced by postprandial refilling, whereas the latter is not influenced by refilling. The aim of this study was to measure postprandial refilling and turnover of bile by combining the two techniques. METHODS: Simultaneous scintigraphy and ultrasonography were used in 14 patients with gallstones and 11 healthy controls. Measurements were performed while the patients were fasting and at 10-minute intervals after a standard meal for 90 minutes, and the measurements were used to calculate postprandial refilling, turnover of bile (in milliliters), and turnover index. RESULTS: Ultrasonography and scintigraphy provided different gallbladder emptying patterns. Compared with controls, patients with gallstones had impaired emptying by both scintigraphy (P < 0.0001) and ultrasonography (P < 0.01). Postprandial refilling and turnover were both reduced between 60 and 90 minutes (P < 0.05), and the turnover index was markedly reduced (1.8 vs. 3.5; P < 0.001). CONCLUSIONS: Simultaneous scintigraphy and ultrasonography provide a new model of gallbladder motor function showing that refilling begins immediately postprandially. In healthy controls, the gallbladder postprandially handles up to six times its basal volume within a period of 90 minutes, but this turnover of bile is markedly reduced in cholelithiasis causing a reduced washout effect of the gallbladder contents, including cholesterol crystals.

Analysis of Variance↗
PubMed1995

Pharmacokinetics of mitoxantrone, etoposide and cytosine arabinoside in leukemic cells during treatment of acute myelogenous leukemia--relationship to treatment outcome and bone marrow toxicity.

Twenty-seven patients with acute myelogenous leukemia (AML) were given remission induction treatment with mitoxantrone, etoposide and cytosine arabinoside (ara-C). The pharmacokinetics in leukemic blood cells of mitoxantrone, etoposide and the active metabolite of ara-C, ara-CTP, were determined during the first day of treatment. There was a large interpatient variability of the area under the time versus concentration curve (AUC) for all three drugs. On the individual level, there was no correlation between the AUCs of the different drugs. Neither did the AUC of any individual drug nor the calculated total intracellular drug exposure have any association with the outcome of treatment or hematological toxicity, measured as duration of leukopenia/thrombocytopenia. In conclusion, when combination chemotherapy with mitoxantrone, etoposide and ara-C is given to patients with AML, intracellular drug concentrations, achieved after the first dose of each drug, do not seem to be predictive for treatment response or hematological toxicity.

Adult↗
PubMed1995

Hyperkeratotic spicules and monoclonal gammopathy.

Hyperkeratotic spicules are a rare disorder that has been associated with different types of malignancies. An association with multiple myeloma raises the question of a relation between the monoclonal component and skin manifestations. We describe hyperkeratotic spicules in a 61-year-old man with a monoclonal gammopathy of undetermined significance. Immunofluorescence and immunoelectron microscopic findings demonstrated the deposition of the monoclonal immunoglobulin at the dermoepidermal junction. Our findings support previous reports that the association between hyperkeratotic spicules and monoclonal gammopathy is not fortuitous and may be related to particular properties of the monoclonal immunoglobulin.

Humans↗
PubMed1995

Inhibition of blood-brain barrier disruption in experimental allergic encephalomyelitis by short-term therapy with dexamethasone or cyclosporin A.

Double radioisotope measurement of neurovascular integrity in Lewis rats inoculated for experimental allergic encephalomyelitis (EAE) showed abnormal elevation of albumin extravasation in the cerebellum, medulla-pons and cervical spinal cord at the time of clinical manifestation. Therapeutically administered dexamethasone (Dex) (0.1-1 mg/kg body weight) or cyclosporin A (CsA) (25-75 mg/kg body weight) dose-dependently reduced albumin movement across the blood-brain barrier (BBB). Dex at a dose of 1 mg/kg completely suppressed abnormal BBB permeability in all tissues (P < or = 0.001), while CsA at the highest dose of 75 mg/kg achieved highly significant (P < or = 0.001), but not complete, suppression of aberrant barrier leakage in the areas studied. The implications of these findings to possible drug action at the immunocompromised cerebrovasculature are discussed.

Animals↗
PubMed1995

Heterosexual behaviour and HIV risk in New Zealand: data from a national survey.

The pattern of any future major heterosexual epidemic of acquired immunodeficiency syndrome (AIDS) will depend partly on sexual behaviour and condom use among heterosexuals. This survey was designed to provide information on patterns of sexual behaviour in New Zealand. A national sample aged 18 to 54 was selected using a random method and telephone interviews were administered to 2361 people, using a questionnaire based on the protocol developed by the Global Program on AIDS of the World Health Organization. The reported mean lifetime number of partners increased with age up to 25 to 29 years for women and 30 to 34 years for men, and declined at older ages. Fifteen or more lifetime partners were reported by 17 per cent of men and 4 per cent of women. Multiple partnerships in the previous 12 months were commonest in those aged 20 to 24. In this age group, 32 per cent of men and 20 per cent of women reported two or more partners. Recent condom use for contraception was reported by 23 per cent of men and 19 per cent of women. Use was highest amongst those aged 18 to 24, and decreased sharply with age. The true proportion of the population with many sexual partners may be higher than reported. These data will be useful in modelling approaches to estimate the likelihood of future heterosexual spread of AIDS. The data on lifetime numbers of partners suggest that sexual decisions depend not just on age and sex but also on the era, and thus on changing social values about sexual behaviour.

Adolescent↗
PubMed1995

Home oxygen therapy. A comparison of 2- vs 6-month patient reevaluation.

STUDY OBJECTIVE: To contrast the effectiveness of 2- vs 6-month reevaluation intervals on both clinical outcome and cost in patients requiring continuous home oxygen therapy (HOT). DESIGN: Prospective, randomized clinical trial. SETTING: The outpatient program of a university-affiliated Veterans Affairs Medical Center (VAMC) Pulmonary Service. PATIENTS: Fifty patients were chosen from among a cohort of 200 patients currently enrolled in our HOT program. All met specific arterial blood gas criteria, were able to give informed consent, had at least 6 months of prior HOT usage, and did not have any illness expected to independently shorten life expectancy. INTERVENTIONS: Baseline resting oxygen flow rates were prescribed based on the results of arterial blood gas measurements so as to attain a PaO2 > 60 mm Hg. Flow rates were adjusted as needed during a 12-min walk to maintain pulse oximetry readings > 90%. No adjustments in baseline flow rates were made during sleep. Identical evaluations were repeated at either 2- or 6-month intervals. MEASUREMENTS AND RESULTS: At 1-year follow-up, there were no significant differences between the 2- and 6-month groups in any of the clinical outcome parameters measured, ie, number of emergency department visits, number of hospitalizations, number of days hospitalized, or mortality. Total costs were not significantly different between the two groups. Evaluation costs were less in the 6-month follow-up group. CONCLUSIONS: After attaining stability following at least 6 months of continuous HOT usage, patients receiving continuous HOT need not be routinely reevaluated more frequently than every 6 months.

Aged↗
PubMed1994

Preparation and preliminary characterization of poly(ethylene glycol)-pepstatin conjugate.

The carboxyl function of pepstatin has been coupled, through an amide bond, to methoxypoly(ethylene glycol) (5 kDa), to which an amino function had been previously grafted. The mPEG-pepstatin conjugate inhibits hog pepsin (aspartic proteinase) in vitro as pepstatin itself, however, with a 400 times higher apparent Ki. The conjugate apparently does not inhibit proteinases belonging to other proteinase families such as serine (trypsin, carboxypeptidase Y), cysteine (Papaya proteinase III), or metallo (collagenase) proteinases.

Carboxypeptidases↗
PubMed1994

Comparison of the intracellular pharmacokinetics of daunorubicin and idarubicin in patients with acute leukemia.

Five patients with acute non-lymphoblastic leukemia were treated with a mixture of daunorubicin 50 mg/m2 and idarubicin 10 mg/m2 given as a short-time infusion. Daunorubicin, idarubicin and the main metabolites daunorubicinol and idarubicinol were separated and the concentrations in plasma and leukemic cells were determined by HPLC. Although idarubicin was given in one-fifth of the dose, the intracellular peak concentration was 70% of that of daunorubicin. The initial elimination of idarubicin from leukemic cells was somewhat faster but in the terminal phase the drug was retained longer than daunorubicin. Intracellular concentrations of both metabolites were low and probably of little importance for the activity of the drug. We conclude that the intracellular pharmacokinetics of idarubicin, with higher peak concentration and longer terminal retention, is a possible explanation for the higher toxicity and suggested better antileukemic effect of this drug.

Acute Disease↗
PubMed1994

Determinants of career choices among women and men medical students and interns.

Women continue to be poorly represented in medical specialties other than general practice. A cross-sectional design was used to explore the development of career plans as medical training progressed; men and women students were compared in their first (n = 316), final (n = 295) and intern (n = 292) years. Women at each stage of training were significantly more likely to choose general practice as the field in which they were most likely to practise. There was little evidence that these differences were influenced by experience during training: women were as likely to choose general practice in first year as in the intern year. The most important determinant of career choice appeared to be the flexibility of training and of practice of medicine: variables such as the opportunity for part-time training, flexible working hours and part-time practice were important determinants of career choice and were of more importance to women than to men. The study also found high rates of discrimination or harassment reported by women medical students and interns. The results indicate the need for continued debate about these issues within medicine and the development of more flexible styles of medical training and practice.

Career Choice↗