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Biomedical subjects

C Peterson

Publications and source records attributed to C Peterson.

At least 145 records · Page 8Linked to original sources

Life after trauma: personality and daily life experiences of traumatized people.

In this study, we explored differences in personality and daily life experiences of traumatized (n = 26) versus nontraumatized (n = 30) college students. Study participants completed a variety of personality measures as well as a 28-day experience sampling study assessing daily activities, emotions, and physical health. Although not differing on general demographics, traumatized individuals reported more trait anxiety and lower self-esteem than nontraumatized individuals. They scored higher on Neuroticism, were more introverted, and were less emotionally stable than nontraumatized participants. Traumatized individuals also reported more cognitive disturbances, emotional blunting, and interpersonal withdrawal. They did not report being more depressed, but did endorse cognitive styles associated with heightened risk for depression. Earlier age of trauma was associated with more pathological outcomes: lower self-esteem and psychological well-being, more anxiety, more pessimism, and emotional constriction of positive mood. We compare this symptom profile to that of posttraumatic stress disorder.

Activities of Daily Living↗

Infection control and human immunodeficiency virus: perceptions of risk among nurses and hospital domestic workers.

In December 1993 the first case of patient-to-patient transmission of human immunodeficiency virus (HIV), at a doctor's surgery in New South Wales, was documented. In an environment of heightened anxiety about HIV transmission and the adequacy of infection-control measures taken by health providers, it is important to explore perceptions of occupational risk of exposure to infection among hospital workers, reasons why hospital domestic workers sometimes depart from standard procedure in infection control, and how they regard the patients who have infectious diseases. In this study, at an infectious diseases hospital where there is an acute awareness of such issues, nurses had accurate knowledge about control of infection, including HIV, but had limited trust of that knowledge. They gave rationales for why they sometimes departed from infection-control procedures. They had low levels of fear of homosexuals and of acquired immune deficiency syndrome. The hospital domestic workers had lower levels of accurate knowledge about infection control, including HIV, and less trust of that knowledge and of protection by health provider from occupational exposure to infection. They had low levels of fear of homosexuals and HIV. Both groups sought regular, small-group, interactive education programs on infection control and HIV to allow them to discuss their concerns. Participatory education of workers should include eliciting concerns of participants, and should discuss concerns regarding administrators' and educators' interests in their safety and wellbeing.

Adult↗

Studies of the organ distribution in mice of teniposide liposomes designed for treatment of diseases in the mononuclear phagocytic system.

Liposomes can be used for the delivery of drugs in cancer chemotherapy. After i.v. injection liposomes are to a large extent taken up by the mononuclear phagocytic system (MPS). When treating diseases in the MPS, such as the histiocytic syndromes, this property is of potential value for drug targeting and may lead to a more efficient therapy with less systemic toxicity. Teniposide (VM-26) is a potent anti-tumor drug. Its lipophilicity makes it suitable for liposomal formulation. Teniposide liposomes were prepared by dissolving egg phosphatidylcholine and dioleoyl phosphatidic acid (19:1 molar ratio) in methylene chloride together with teniposide. After solvent evaporation, the dry lipid film was dispersed in a glucose solution (50 mg/mL), and size calibration was obtained by filtration through polycarbonate filters. The amount of teniposide incorporated was 2.5 mol%. To investigate the organ distribution, teniposide liposomes containing radiolabeled teniposide or phospholipid were given i.v. to mice. By increasing the size of the vesicles, the MPS uptake could be modulated. When vesicles of 200 nm and 1 and 3 microns were injected, the drug levels in the spleen were increased 2.6-, 6.8-, and 21-fold 40 min after injection, compared with levels after injection of the commercial teniposide formulation. It was concluded that organ distribution of teniposide in mice could be modified by administering the drug in liposomal form with the potential of improved treatment of diseases engaging the MPS.

Animals↗

Multidrug resistance (Mdr1) gene expression in peripheral blasts from patients with acute leukemia only rarely increases during disease progression after combination chemotherapy.

Multidrug resistance gene (mdr1) RNA levels were determined in 55, and P-glycoprotein expression in 37 samples of peripheral leukemic cells from 17 patients with acute myeloblastic leukemia (AML) and 7 patients with acute lymphocytic leukemia (ALL). Between sample collections, patients were treated with various chemotherapy regimens. Mdr1 RNA levels were quantified by a RNA-RNA solution hybridization assay. P-glycoprotein was determined by Western blot analysis. Samples from 14 patients (9 AML, 5 ALL) had undetectable mdr1 RNA levels at initial analysis. Only two of these had detectable levels after chemotherapy. Ten patients (8 AML, 2 ALL) had detectable mdr1 RNA levels at initial analysis (median 1.0 transcript per cell, range 0.2-1.4). Increase of mdr1 RNA levels after chemotherapy were observed in cells from 3 patients, one patient had a lower level after chemotherapy and the 6 remaining patients had essentially unchanged mdr1 RNA levels in their leukemic cells. Samples from 13 patients were sequentially analysed for P-glycoprotein expression. In one patient, no P-glycoprotein was detectable at initial analysis but was weakly positive after chemotherapy. In the remaining 12 patients, P-glycoprotein levels stayed stable during disease progression. In conclusion, combination chemotherapy seems only rarely to be associated with an increase of mdr1 gene expression in residual leukemic cells. The addition of resistance modifiers to chemotherapy in order to overcome P-glycoprotein mediated resistance might therefore be more effective in chemotherapy naive patients since it is possible that during later disease progression additional mechanisms of resistance may be more operative.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Targeting of teniposide to the mononuclear phagocytic system (MPS) by incorporation in liposomes and submicron lipid particles; an autoradiographic study in mice.

Liposomes are concentrated in the mononuclear phagocytic system in vivo and may therefore be of value as carriers of drugs when treating diseases involving phagocytic cells. Teniposide (VM-26) is a potent and lipophilic cytotoxic drug. Teniposide was incorporated in large unilamellar liposomes (LUVs) consisting of egg phosphatidylcholine and dioleoyl phosphatidic acid and into the novel submicron lipid particles containing cholesteryl oleate, cholesteryl palmitate and soybean lecithin, in order to evaluate the drug targeting effect. Radiolabelled teniposide and lipids were used and the organ distribution in mice was studied with whole-body autoradiography 20 and 90 min post i.v. injection. When the commercial formulation of teniposide (Vumon) was administered, teniposide accumulated in the liver where the drug is metabolized. Biliary excretion was rapid and considerable already after 20 min. The liposomal formulation enhanced liver uptake of teniposide slightly. The distribution of radiolabelled phosphatidyl choline differed from that of teniposide indicating instability of the liposomes in circulation. Despite this, the splenic uptake of the drug was significantly enhanced by administration in liposomes. In the red pulp of the spleen the teniposide level was 23 times higher 90 min post injection, using the liposomal formulation as compared to free drug. The submicron lipid particles were mainly accumulated in the liver and to a lesser extent in the spleen. The study shows that liposomes and lipid particles enhance splenic and liver uptake and can be used to target teniposide to the MPS.

Animals↗

Defining the core content of general practice in Australia.

The nature and quality of general practice care affect the health of almost all Australians. However, the enormous and changing scope of general medical services in this country has not been adequately defined. What the core content of these services should be, cannot be determined without first considering how such an evaluation can best be made. Therefore, this article suggests an approach to defining the core components of Australian general practice care based on four types of need: normative need, felt need, expressed need and comparative need. Each type contributes to defining the minimum services and skills that every practising general practitioner should be able to provide.

Australia↗

Acetic aldehyde and formaldehyde in cutting fluids and their relation to irritant symptoms.

The objective was to study the formation of acetic aldehyde in cutting fluids and its relation to irritation of mucous membranes and the skin. Acetic aldehyde and formaldehyde were analysed in two large cutting fluid systems in an engineering industry. Samples were taken 1-5 times a week during a year. Concentration of the cutting fluid, leakage oils, pH, bacteria, yeast and fungi were analysed weekly. The occurrence of mucous membrane irritation was registered through questionnaires to the exposed workers. About 50 persons were exposed to each of the cutting fluids. The concentration of the aldehydes varied with time and between the cutting fluids. None of the analysed parameters could explain the variable concentration of aldehydes. Mucous membrane irritation was much more common in one of the systems, e.g. the prevalence of irritation in the nose was about 30-40% in workers exposed to a cutting fluid, while the corresponding prevalence was less than 10% in workers exposed to another fluid. The occurrence of symptoms was slightly associated with the concentration of aldehydes and pH of the fluid varied more in the fluid that caused most symptoms. A few measurements of ammonia indicated a higher concentration of ammonia in the fluid that caused most symptoms. It is concluded that irritation of mucous membranes and the skin may vary considerably between different cutting fluids of similar composition and use but the causal factor could not be determined in this study, but a variable pH and an increased concentration of ammonia may be indicators in this context. The concentration of acetic aldehyde vary with time and between cutting fluids with similar composition. A high variability may be an indicator of less stable cutting fluids. Better markers for the surveillance of cutting fluids needs to be developed as well as a health control programme.

Acetaldehyde↗

Cloning the Drosophila homolog of the xeroderma pigmentosum complementation group C gene reveals homology between the predicted human and Drosophila polypeptides and that encoded by the yeast RAD4 gene.

A human xeroderma pigmentosum group C (XPC) cDNA has been previously isolated by functional complementation (Legerski and Peterson, Nature, 359, 70-73, 1992). Sequence analysis did not reveal protein motifs which might suggest a possible biochemical function for the putative XPC protein. In order to identify functional domains in the translated XPC sequence the homologous gene from Drosophila melanogaster, designated XPCDM, was cloned by DNA hybridization. Sequence analysis of an apparently full-length cDNA revealed an open reading frame which can encode a predicted polypeptide of 1293 amino acids. Significant homology of the C-terminal 346 amino acids with both the human XPC and Saccharomyces cerevisiae Rad4 protein sequences is observed, suggesting that these proteins are functional homologs.

Amino Acid Sequence↗

Chloroquine reduces the bioavailability of methotrexate in patients with rheumatoid arthritis. A possible mechanism of reduced hepatotoxicity.

OBJECTIVE: To evaluate the effects of a single dose of chloroquine (CQ) on the pharmacokinetics of methotrexate (MTX) in patients with rheumatoid arthritis. METHODS: Eleven patients (ages 41-75 years) who were taking oral doses of MTX (15 mg/week) were studied after a dose of MTX alone and after a dose of MTX plus CQ (250 mg). Plasma and urine samples were collected for 24 hours after dose intake, and the concentrations of MTX and its major metabolite 7-hydroxymethotrexate were determined by high-performance liquid chromatography. RESULTS: Administration of CQ together with MTX caused a reduction in the area under the plasma MTX concentration versus time curve (AUC). The median value of individual AUC ratios (MTX/MTX + CQ) was 1.6 (95% confidence interval 1.2-3.6). CONCLUSION: The most likely mechanism for the interaction is that CQ reduces the bioavailability of MTX. This gives a possible explanation for a suggested reduction in MTX-associated liver toxicity by coadministration of CQ. The significance of the interaction for the therapeutic effect remains to be elucidated.

Adult↗

Evaluation of the antipyretic effect of ketorolac, acetaminophen, and placebo in endotoxin-induced fever.

The authors studied the antipyretic effect of three intramuscular doses of ketorolac (15, 30, and 60 mg), acetaminophen 650 mg PO, and placebo in healthy male volunteers using an endotoxin-induced fever model. In this double-blind, double-dummy, parallel study, subjects were assigned randomly with equal probability to one of the above treatment groups. Thirty minutes after study medication administration, a 20 unit per kilogram dose of reference standard endotoxin (RSE) was administered intravenously, and temperature was determined every 15 minutes for an 8-hour period. Compared with placebo, all active treatment groups demonstrated a statistically significant reduction in both adjusted area under the temperature-by-time curve (AAUC) and the maximum increase over baseline temperature (dTmax). Furthermore, the 30 mg intramuscular dose of ketorolac demonstrated approximately the same antipyretic activity as the 650 mg oral dose of acetaminophen, and there was a statistically significant dose response across the three ketorolac doses studied (P < .0001). The majority of side effects reported during this study were symptoms associated with fever, including chills, headache, myalgia, and dizziness, all of which are effects of RSE. The frequency of side effects tended to be less in the treatment groups with the greatest antipyretic activity.

Acetaminophen↗

Plasma and urine levels of methotrexate and 7-hydroxymethotrexate in children with ALL during maintenance therapy with weekly oral methotrexate.

A new high-performance liquid chromatographic assay was used to determine methotrexate (MTX) and its main metabolite, 7-hydroxymethotrexate (7-OH-MTX), in the plasma (n = 17) and urine (n = 14) of children (age 3-12 years) on maintenance therapy for acute lymphocytic leukemia (n = 14) or non-Hodgkin's lymphoma (n = 3). Each child received oral doses of weekly MTX (4.0-29 mg/m2) and daily 6-mercaptopurine (40-111 mg/m2). Plasma samples were collected daily from two children during the 1-week dose interval. A limited sampling strategy was designed, whereby 2 days of blood sampling were used in the other 15 patients. Morning urine samples were collected daily for 1 week following MTX intake from 14 of the children. MTX was detectable in all plasma and urine samples for the entire dose interval. The main metabolite, 7-OH-MTX, could be detected in plasma and urine from all patients on the first day after dose intake but only in a few patients during the whole dose interval. Interpatient variability of MTX and 7-OH-MTX levels was high at all points during the week. Significant correlation were found between the urinary MTX levels on days 2 and 7 and plasma MTX levels on day 2 after intake. No significant correlation was found between drug levels in plasma or urine and liver function tests in the children showing signs of mild liver injury. This assay provides a tool for further studies on the role of pharmacokinetics for the clinical effects of weekly oral low-dose MTX given alone or in combination with 6-mercaptopurine.

Administration, Oral↗

Delayed chemotherapy-induced nausea is augmented by high levels of endogenous noradrenaline.

The relation between pretreatment night-time urinary catecholamine excretion and chemotherapy-induced nausea and vomiting was studied. The first cohort included 17 women and three men with various cancer forms receiving low or moderately emetogenic chemotherapy. The second cohort included 42 women receiving cisplatinum (50 mg m-2) for ovarian cancer and ondansetron as an antiemetic (8 mg i.v. x 3 at chemotherapy and 8 mg p.o. x 3 for 5 days). Relatively higher noradrenaline, but not adrenaline, excretion was associated with an increased intensity of delayed nausea following treatment. Vomiting was not consistently related to the excretion of either catecholamine. The results indicate that noradrenaline modulates delayed nausea resulting from chemotherapy.

Adult↗

Methotrexate in rheumatoid arthritis--a limited sampling strategy for estimation of the area under the plasma concentration versus time curve.

A limited sampling strategy for determination of the area under the plasma concentration versus time curve (AUC) of methotrexate (MTX) in patients with rheumatoid arthritis (RA), treated with weekly oral doses, has been validated. Stepwise linear regression analysis was used for optimal inclusion of data points in mathematical models to estimate AUC. A new plot for evaluation of the accuracy and precision of the estimated AUC values was introduced in the present study. By plotting the ratio of determined/estimated AUC values versus estimated AUC values, the influence of number of sampling points on the precision and accuracy of estimated AUC values was easily validated. Our results show that AUC values of MTX in RA patients can be estimated from a single plasma sample at 3 h or preferably, due to increased precision, by additional samplings at 5 and 1 h. A further increase of the number of sampling points increased the precision of the AUC estimates only to a minor extent. The accuracy of the estimated AUC values was independent of the number of sampling points. A limited sampling procedure can now be used for further studies on the relationship between MTX levels and its effects.

Administration, Oral↗

Releasability of human hypereosinophilic eosinophils is related to the density of the cells.

The activity of eosinophils and neutrophils with respect to the release of granule proteins was studied in 11 patients with the hypereosinophilic syndrome (HES). Granulocytes or purified eosinophils were stimulated with serumopsonized Sephadex particles (C3b-induced release), and the released amounts of eosinophil cationic protein (ECP), eosinophils protein-X (EPX) and myeloperoxidase (MPO) were measured by means of specific radioimmunoassays (RIA). Eosinophils obtained from patients with HES released significantly more ECP (P < 0.002) and EPX (P < 0.01) after 20 min of incubation than cells from the control group. The cellular content of ECP and EPX in eosinophils obtained from the patients with HES was significantly reduced to 50% and 62%, respectively, of the content of these granule proteins of eosinophils from the control group. In separated eosinophils light-density eosinophils released more of both ECP and EPX than normal density eosinophils. There was no difference in MPO release between the patients and the control group. We conclude that the eosinophils from patients with HES have an increased propensity to release their granule proteins and the releasability seems to be related to the density of the cells.

Adolescent↗

Increased intracellular concentrations of doxorubicin in resistant lymphoma cells in vivo by concomitant therapy with verapamil and cyclosporin A.

The tumor cell uptake of doxorubicin was studied in vivo in cells from 2 patients with clinically resistant leukemic lymphomas treated with continuous infusions of doxorubicin 9 mg/m2 and vincristine with oral dexamethasone. After 24 hours, intravenous or oral verapamil was added and in one treatment course intravenous cyclosporin A was given. Plasma and intracellular doxorubicin concentrations and plasma concentrations of verapamil and norverapamil were determined with HPLC. In the 1st patient the intracellular uptake rate of doxorubicin was increased from 0.007 to 0.013 nmol/mg protein/h after the start of verapamil infusion. In the first treatment course of patient number 2, the intracellular concentration of doxorubicin was increased by 280% during a 6-h infusion of verapamil. When this patient in the next treatment course was given oral verapamil, no significant effect on doxorubicin uptake was seen. However, when 100 mg of cyclosporin A was added in three intravenous injections at 8-h intervals, the doxorubicin concentration in the tumor cells increased from 0.027 to 0.086 nmol/mg protein. In conclusion, this study shows that the intracellular concentrations of doxorubicin can be increased also in vivo during patient therapy by the addition of verapamil or cyclosporin A.

Adult↗

IS WALKING COSTLY FOR ANURANS? THE ENERGETIC COST OF WALKING IN THE NORTHERN TOAD BUFO BOREAS HALOPHILUS

Locomotor mode and the maximal capacity for aerobic metabolism are thought to be co-adapted in anuran amphibians. Species that rely heavily on walking often have high capacities for aerobic metabolism relative to species that rely primarily on saltation. We tested the hypothesis of co-adaptation of gait and aerobic metabolism by investigating the locomotor energetics of Bufo boreas halophilus, a toad that walks, but does not hop. Rates of oxygen consumption during locomotion were measured in an enclosed variable-speed treadmill. The steady-state rate of oxygen consumption (V(dot)O2ss) increased linearly within a range of sustainable speeds [V(dot)O2ss (ml O2 g-1 h-1) = 0.93 x speed (km h-1) + 0.28]. The minimum cost of transport, Cmin (the slope of this relationship), varied significantly among individual toads. When expressed in units of oxygen consumed per distance travelled (ml O2 km-1), Cmin scaled isometrically with body mass: Cmin = 0.69mass1.07. Consequently, mass-specific Cmin (ml O2 g-1 km-1) was uncorrelated with body mass. Variation in Cmin was also unrelated to experimental temperature. Mass-specific Cmin estimates were similar to previous allometric predictions for terrestrial animals of similar size, which contrasts with previous findings for another toad species. Maximum rates of oxygen consumption measured in closed, rotating respirometers were significantly higher than the maximum rates achieved on the treadmill, but lower than those measured previously in other Bufo species. Our results indicate that walking is not necessarily a costly gait for toads and that high maximum rates of oxygen consumption are not associated with reliance on walking within the genus Bufo.

Journal Article↗

Twelve-year follow-up of respondents in a sample survey in Peninsular Malaysia.

"This note reports the experience of an attempt to find and re-interview in late 1988 and early 1989, as part of the Second Malaysian Family Life Survey (MFLS-2), the female respondents to the 1976-77 Malaysian Family Life Survey (MFLS-1) and a sample of their adult children aged 18 or older.... We discuss the field methods used to track the panel members and their adult children, report follow-up rates and analyze the selectivity of attrition from the panel, using data from the MFLS-1 on characteristics of both the missing and the re-interviewed respondents and their families. We then discuss the degree to which these results might be generalized to other such attempts at re-contacting survey respondents."

Asia↗

A non-P-glycoprotein-mediated mechanism of vincristine transport which is affected by resistance modifiers and present in chemosensitive cells.

The accumulation and cytotoxicity of vincristine (Vcr), etoposide (VP16), and daunorubicin (Dau) and effect of the resistance modifiers (RM) verapamil (Ver; 10 microM) and cyclosporin A (CyA; 3 microM) were studied in isolated rat cardiac myocytes, peripheral lymphocytes from seven patients with chronic lymphocytic leukemia (CLL), in the human leukemic cell line K562 and its two Vcr resistant mdr1 gene expressing sublines, K562/Vcr30, K562/Vcr150. Both RMs increased the accumulation and cytotoxic effect of Vcr and Dau in the resistant sublines. In K562 cells, lymphocytes from patients with CLL and rat cardiac myocytes, which all were mdr1 RNA negative RMs increased the cellular accumulation and potentiated the cytotoxic effect of Vcr but not that of Dau. K562/Vcr30 and K562/Vcr150 were cross resistant to Dau but not to VP16 and RMs had no effect on the cytotoxicity of VP16 in any of cell lines. The results indicate that chemosensitive cells also have a transport mechanism, not mediated by P-glycoprotein, which transports Vcr but not Dau and VP16. This suggests that addition of RMs to Vcr-containing chemotherapy may enhance the antineoplastic effect also by inhibition of non-P-glycoprotein mediated transport mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗