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Biomedical subjects

C Paul

Publications and source records attributed to C Paul.

At least 109 records · Page 6Linked to original sources
PubMed1999

EMLA cream as a topical anesthetic for the repeated mechanical debridement of venous leg ulcers: a double-blind, placebo-controlled study.

BACKGROUND: A granulating surface is important for skin grafting and healing of leg ulcers. Mechanical debridement to remove necrotic tissue often must be stopped before completion because of pain. OBJECTIVE: Our purpose was to assess the effect of EMLA cream on the number of debridements required to obtain a clean ulcer and on pain during debridement and to determine its safety after repeated doses. METHODS: In this randomized double-blind, placebo-controlled study, 69 patients with venous leg ulcers received cream before debridement until a clean ulcer was obtained (or a maximum of 15 debridements). RESULTS: EMLA decreased the median number of debridements required for a clean ulcer (EMLA 11.5, placebo >15; P = .019) and decreased pain by 50% (P = .003). Plasma levels of lidocaine, prilocaine, and their main metabolites were low without any apparent accumulation. CONCLUSION: EMLA produces effective pain relief for the debridement of leg ulcers and shortens the time to a clean ulcer.

Administration, Cutaneous↗
PubMed1999

Intermittent short courses of cyclosporin (Neoral(R)) for psoriasis unresponsive to topical therapy: a 1-year multicentre, randomized study. The PISCES Study Group.

We performed a 1-year study to determine whether intermittent short courses of the microemulsion formulation of cyclosporin (Neoral) could effectively control plaque psoriasis and whether tapering or abrupt cessation of cyclosporin therapy would influence time to relapse. Four hundred patients with plaque psoriasis were included in this open, multicentre, randomized study. All patients commenced cyclosporin at a dose of 2.5 mg/kg daily. Cyclosporin dosage could be increased to a maximum of 5 mg/kg daily. Treatment was continued until clearance of psoriasis or for a maximum of 12 weeks. Patients were then randomly assigned either to stop cyclosporin abruptly or to have the dose reduced by 1 mg/kg daily each week until cessation. On relapse, patients were given another course of cyclosporin. Patients were followed for at least 1 year, during which they could receive as many treatment courses as necessary. The number of patients who required one, two, three and four treatment courses was 400, 259, 117 and 26, respectively. The median time to relapse after the end of the first treatment period was 109 days in the group of patients randomized to stop cyclosporin abruptly and 113 days in patients randomized to taper off cyclosporin (P = 0.038). More than 30% of patients had not relapsed 6 months after having stopped treatment. After each treatment course, the Kaplan-Meier probability of achieving 75% or more reduction in disease area by day 84 of treatment was 83%, 76%, 73% and 66%, respectively. Mean serum creatinine concentration and blood pressure did not show any clinically significant changes over time. Our results show that intermittent short-course therapy with Neoral, when used in conjunction with topical therapy, is well tolerated and provides effective control of plaque psoriasis for 1 year. Tapering off cyclosporin on treatment cessation induces a slight delay in psoriasis relapse.

Adolescent↗
PubMed1999

A prospective coagulation study including resistance to activated protein C and mutations in factors V and II in venous leg ulcers.

Hypercoagulable states have been reported to be associated with venous leg ulcers. In an attempt to investigate the prevalence of hypercoagulable states in patients with venous leg ulcers, we performed a prospective case-control study for the presence of coagulation defects in such patients, including resistance to activated protein C (APC), factor V Leiden mutation and a newly described mutation in factor II. Results were compared with those obtained in a control group. APC resistance was found in four of 33 patients tested, but only one was found to be heterozygous for the factor V Leiden mutation. Factor II mutation was found in two of 30 patients tested. Our findings show that the prevalence of coagulation abnormalities is not different in patients with venous leg ulcers from controls in our study, suggesting that only selected patients with venous ulcers and a history of recurrent deep venous thrombosis should be investigated for the presence of coagulation defects.

Activated Protein C Resistance↗
PubMed1999

Breast cancer in Maori and non-Maori women.

BACKGROUND: Breast cancer is more common in Maori than in non-Maori women under the age of 40 years and is equally common in older women, despite Maori being generally of lower socioeconomic status and having had a higher fertility rate than non-Maori. METHODS: Data from a nationwide population-based case-control study of breast cancer in New Zealand women aged 25-54 years were used to compare the age-adjusted distribution of reproductive and other risk factors for breast cancer in self-identified Maori and non-Maori women from the control group. Separate analyses also were carried out for women aged 25-39 years and for those aged 40-54 years. The risk of breast cancer according to the proportion of Maori ancestry was estimated using multiple logistic regression simultaneously adjusting for several risk factors. RESULTS: Significant differences were found between self-identified Maori and non-Maori women in the age-adjusted frequencies for education level, socioeconomic status, age at first full-term pregnancy, parity, and duration of breastfeeding; the profile in all instances suggesting a lower risk of breast cancer for Maori than for non-Maori. There were no significant differences with respect to age at menarche, surgery for benign breast disease or a family history of breast cancer. Significantly more Maori than non-Maori were in the highest quartile of recent body mass index. Women self-identified as Maori has an approximately twofold higher risk of breast cancer than non-Maori women. CONCLUSIONS: Maori have high rates of breast cancer despite having a more favourable profile than non-Maori for most identified risk factors.

Adult↗
PubMed1999

Waiting for elective surgery: effects on health-related quality of life.

OBJECTIVE: To describe the experiences of people required to wait for admission to a New Zealand regional hospital to receive elective surgery. DESIGN: Cross-sectional. SETTING: Eligible people were invited to participate in a face-to-face interview with one of us in their own home or in a private office at the University of Otago. STUDY PARTICIPANTS: The study population comprised all people on the waiting list for prostatectomy or hip or knee joint replacement. Of those who were eligible and contacted, 89% of men (n=102) on the prostatectomy waiting list and 92%. of people (n = 47) on the hip/knee joint replacement waiting list were interviewed. Main outcome measures. Participants completed the SF-36 health survey to measure general health-related quality of life and condition-specific instruments to measure the severity of each participant's condition. Participants were also asked questions concerning acceptable waiting times. RESULTS: The majority of participants reported severe symptoms and significantly poorer health-related quality of life on most dimensions than a general sample of the New Zealand population. Neither general quality of life nor condition-specific health appeared to worsen with the duration of wait, but this may have been an effect of the study design. People with more severe symptoms desire surgery more quickly than people with less severe symptoms. The lengthy wait for surgery experienced by many participants represents a burden in terms of living with the unrelieved severe symptoms and poor health-related quality of life.

Cross-Sectional Studies↗
PubMed1999

Knowledge and perceptions about breast cancer incidence, fatality and risk among Australian women.

OBJECTIVE: Breast cancer is the most common fatal cancer among Australian women. This study aimed to provide an accurate national picture of women's understanding of breast cancer incidence, fatality and risk. METHOD: A telephone survey explored the knowledge and perceptions of a sample of 2,935 Australian women in relation to breast cancer incidence, fatality, risk factors, risk perception and level of concern. RESULTS: Australian women were well aware of breast cancer in general terms, however, there were major aspects of incidence and risk which were poorly understood. Only 5% of women nominated age as a risk factor, and only one-third were able to make an approximately correct estimate of the incidence of breast cancer in Australia. CONCLUSIONS AND IMPLICATIONS: Recommendations for future information campaigns include targeting understanding of lifetime risk of developing breast cancer, age as a risk factor, survival from breast cancer and the need to separately address the perceptions of older versus younger women.

Adult↗
PubMed1999

Long-term clinical follow-up in 265 patients with deep venous thrombosis initially treated with either unfractionated heparin or dalteparin: a retrospective analysis.

The primary objective of this retrospective study was to describe the frequency of a post-thrombotic syndrome in 265 patients previously treated for deep venous thrombosis (DVT). The secondary objectives were to document the frequency of recurrent venous thromboembolism (VTE) and mortality, especially from malignant disease. The patients were evaluated 5-14 years after inclusion in three randomized trials comparing continuous intravenous (i.v.) infusion of unfractionated heparin (UFH) (n = 85) with a low molecular weight heparin (LMWH), dalteparin (n = 180). The median post-thrombotic score at follow-up was 2 (range 0-8). In a multiple step-wise regression analysis the postthrombotic score was significantly higher among patients with initial proximal DVT (p = 0.0001) as compared with those who had distal DVT. A recurrent venous thromboembolic event was diagnosed in 29.4% of the patients treated with dalteparin and in 23.5% of the patients treated with UFH (ns). A secondary risk factor for venous thromboembolism and a longer duration of treatment with oral anticoagulants (OAC) were significantly associated with a lower risk for recurrent VTE, whereas malignant disease diagnosed during follow-up was associated with a higher risk. During follow-up a total of 40.7% of patients had died. No difference in total mortality or mortality from malignant disease was demonstrated between the two drugs. In conclusion, a severe post-thrombotic syndrome occured relatively infrequent. considering the long observation period. Proximal DVT was significantly associated with a more severe post-thrombotic syndrome. After 14 years follow-up, no significant differences were observed in overall mortality, mortality from malignant disease or recurrent VTE between UFH- and dalteparin-treated patients. Malignant disease was a risk factor for recurrent VTE, the presence of a secondary risk factor and a longer duration of treatment with OAC decreased the risk for recurrent VTE.

Anticoagulants↗
PubMed1998

Growth hormone-mediated transcriptional activation of the rat serine protease inhibitor 2.1 gene involves both interleukin-1 beta-sensitive and -insensitive pathways.

Growth hormone (GH)-dependent activation of the rat serine protease inhibitor 2.1 (spi 2.1) gene in vivo requires both a modification of the chromatin structure and the activation of transcription factors mediated by the tyrosine protein Janus kinase JAK2. To address the question of the relationship between those two GH effects, we used interleukin 1 beta (Il-1 beta) that was previously shown to inhibit spi 2.1 gene expression. In cultured hepatocytes from normal rats, Il-1 beta did not antagonize GH-dependent stimulation of promoter activity (i.e., in episomal constructs) mediated by transcription factors activated by JAK2. In hepatocytes from inflamed rats, GH triggered JAK2-dependent activation of transcription factors as in control cells but failed to stimulate genomic spi 2.1 gene expression. It thus appears that the Il-1 beta-insensitive activation of transcription factors by GH is independent of its action on the nucleosomal structure of the spi 2.1 gene which, in contrast, is sensitive to this cytokine.

Animals↗
PubMed1998

Single-voxel proton magnetic resonance spectroscopy of the pons and cerebellum in patients with schizophrenia: a preliminary study.

Magnetic resonance spectroscopy (MRS) is a non-invasive functional imaging technique that can measure various brain tissue metabolites such as N-acetylaspartate (NAA), choline (Cho), creatine-phosphocreatine (Cr), myo-inositol (mI) and other metabolites. Morphological studies have indicated the pons and cerebellum as possible sites of abnormal functioning in schizophrenic patients. This study examines schizophrenic patients for the presence of abnormalities in proton MRS (1H-MRS) measured metabolites in two regions of the posterior fossa. Twelve schizophrenic patients and eight non-schizophrenic control subjects were studied by measuring the ratios of NAA/Cr, Cho/Cr and mI/Cr from 1H-spectra obtained from the pons and right or left cerebellum using an integrated MRI/MRS protocol. Spectra were obtained from a voxel in the pons and voxels from the left and/or right lateral cerebellum. Data were analyzed in the absorption mode and fitted to Lorentzian lineshapes using a Marquart algorithm. Significantly lower NAA/Cr ratios were found in the pons of schizophrenic patients than in the control subjects, but not in the cerebellum. This study is the first to measure brain tissue metabolites using 1H-MRS in the pons and cerebellum of schizophrenic patients. Significant alterations of 1H-MRS metabolites may suggest the involvement of the posterior fossa as a part of the pathological substrate underlying schizophrenia.

Adult↗
PubMed1998

Characterization of three transcriptional repressor sites within the 3' untranslated region of the rat serine protease inhibitor 2.3 gene.

The activity of the rat serine protease inhibitor 2.3 gene (spi 2.3) is controlled by several positive promoter elements [Simar-Blanchet, A.-E., Paul, C., Mercier, L. & Le Cam, A. (1996) Eur. J. Biochem. 236, 638-648] and a negative element located in the 3' untranslated gene region (3' UTR) [Le Cam, A. & Legraverend, C. (1996) Eur. J. Biochem. 231, 620-627]. In the present studies, we dissected the 348-bp spi 2.3 3' UTR silencer to precisely define repressor sites and look for specifically interacting proteins. Three short elements referred to as A (nucleotides 1751-1776 in the cDNA), B (nucleotides 1812-1827) and C (nucleotides 1958-1974) sites repressed transcription from the homologous spi 2.3 promoter as well as from a heterologous minimal promoter containing the spi GAGA box enhancer. All three sites harbor a (TTTC) motif whose mutation affected silencer activity that was also dependent on flanking sequences. Those sites share the (TTTC) motif and a CCAAT/enhancer-binding-protein(C/EBP)-binding site with a fatty-acid-binding-protein gene promoter element shown to interact specifically with a transcriptional repressor [He, G. P., Muise, A., Wu Li, A. & Ro, H.-S. (1995) Nature 378, 92-96]. This repressor is however unlikely to mediate spi 2.3 3' UTR silencer action since it was not detected in rat hepatocytes. In vitro footprinting of the spi 2.3 3' UTR silencer region revealed a strong interaction with liver nuclear proteins. Among the six identified footprints, three of them (F-II, FIII and F-IV) bound C/EBPs and mapped in regions harboring the repressor function. Binding of C/EBPs to all three spi 2.3 3' UTR repressor sites, although rather weak, was confirmed by electrophoretic mobility shift assays that otherwise failed to reveal specific interactions with other liver nuclear proteins in vitro. However, none of the most largely liver expressed C/EBP species (i.e. alpha, beta and delta) activated the spi 2.3 3' UTR silencer function in NIH 3T3 cells, suggesting that binding of those transcription factors did not mediate the transcriptional repression.

3T3 Cells↗
PubMed1998

Tumor efficacy and bone marrow-sparing properties of TER286, a cytotoxin activated by glutathione S-transferase.

TER286 is a latent drug activated by human glutathione S-transferase (GST) isoforms P1-1 and A1-1 to produce a nitrogen mustard alkylating agent. M7609 human colon carcinoma, selected for resistance to doxorubicin, and MCF-7 human breast carcinoma, selected for resistance to cyclophosphamide, both showed increased sensitivity to TER286 over their parental lines in parallel with increased expression of GST P1-1. In primary human tumor clonogenic assays, the spectrum of cytotoxic activity observed for TER286 was both broad and unusual when compared to a variety of current drugs. In murine xenografts of M7609 engineered to have high, medium, or low GST P1-1, responses to TER286 were positively correlated with the level of P1-1. Cytotoxicity was also observed in several other cell culture and xenograft models. In xenografts of the MX-1 human breast carcinoma, tumor growth inhibition or regression was observed in nearly all of the animals treated with an aggressive regimen of five daily doses. This schedule resulted in a 24-h posttreatment decline in bone marrow progenitors to 60% of control and was no worse than for a single dose of TER286. These studies have motivated election of TER286 as a clinical candidate.

Animals↗
PubMed1998

Reproductive factors and breast cancer in New Zealand.

A national population-based case-control study was used to assess the influence on breast cancer risk of reproductive factors and the possibility of an interaction with age at diagnosis. 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. There was a declining risk of breast cancer with increasing age at menarche (p = 0.06), the strongest effect being seen in women aged less than 40. Parous women had a 27% lower risk of breast cancer than nulliparous women, a reduced risk being evident in all but the youngest age group. A falling risk of breast cancer with rising parity was clear only in women diagnosed when aged at least 45 years. Breast cancer risk tended to fall amongst parous women with increasing duration of breastfeeding (p = 0.14); the association was most apparent in the youngest women, while those over 40 years at diagnosis showed no clear negative trend. There was no association of breast cancer risk with age at first full-term pregnancy, time since last full-term pregnancy, abortion (spontaneous or induced), abortion before first full-term pregnancy, or ability to conceive, and there was no trend in risk with age at natural menopause. Women in the highest category of body mass index at age 20 had the lowest risk of breast cancer in the age group studied. When each reproductive factor was formally tested for effect modification by age at diagnosis, the interaction term in logistic models approached statistical significance only for parity (p = 0.07).

Adult↗
PubMed1998

Immunodominant minor histocompatibility antigen peptides recognized by cytolytic T lymphocytes primed by indirect presentation.

BACKGROUND: Indirect presentation of minor histocompatibility antigens (HA) as revealed by cross-priming of H2 heterozygous recipients effectively primes minor HA-specific cytolytic T lymphocytes (CTLs). However, it is not known if indirect priming generates CTLs specific for the same set of immunodominant minor HA recognized by CTLs primed by direct spleen cell injections. METHODS: In order to indirectly prime minor HA-specific CTLs, we implanted (C57BL/6 x B6.C-H2d)F1 recipients with BALB.B and BALB/c splenocytes loaded into immunoisolation devices that effectively preclude direct donor:host contact. Responder spleen cells from these recipients were stimulated in vitro to expand BALB.B- and BALB/c-specific CTLs to reveal classical cross-priming. RESULTS: Tests of CTL specificity using (1) CXB recombinant inbred strain targets that express different arrays of BALB/c minor HA and (2) high-performance liquid chromatography fractions of peptides from BALB.B Kb and Db molecules revealed that anti-BALB.B CTLs were specific for two previously identified dominant peptides, CTT-2 and CTT-5, presented by Kb molecules. Variation of responders and priming cells resulted in CTL responses to additional dominant peptides that had been identified previously with CTLs generated by direct priming with spleen cell injections. Indirect priming was not limited to this set of peptides recognized by CTLs in vitro because devices loaded with cells devoid of the CTL-detected peptides primed for accelerated skin allograft rejection. CONCLUSIONS: Indirect presentation of minor HA in vivo stimulates the generation of CTLs specific for a subset of dominant minor HA peptides recognized by CTLs primed by direct presentation.

Animals↗
PubMed1998

First sexual intercourse: age, coercion, and later regrets reported by a birth cohort.

OBJECTIVES: To investigate how age at first sexual intercourse is related to the reported circumstances and to determine how these corresponded to views in early adulthood about its timing. DESIGN: Cross sectional study within a birth cohort using a questionnaire presented by computer. SETTING: Dunedin, New Zealand in 1993-4. SUBJECTS: 477 men and 458 women enrolled in the Dunedin Multidisciplinary Health and Development Study, comprising 92% of survivors of the cohort. RESULTS: The median age at first intercourse was 17 years for men and 16 years for women. Only one man (0.2%) but 30 (7%) women reported being forced to have intercourse on the first occasion. For women, there were increasing rates of coercion with younger age at first intercourse. More men than women reported that they and their partner were equally willing (77% (316/413) v 53% (222/419)). Mutual willingness of both partners was greater for those who reported that it was also the first time for their partner. Timing of first intercourse was considered about right by 49% (200/411) of men and 38% (148/388) of women. Many women (54% (211/388) reported that they should have waited longer, and this rose to 70% (90/129) for women reporting intercourse before age 16. CONCLUSIONS: Most women regretted having sexual intercourse before age 16. First intercourse at younger ages is associated with risks that are shared unequally between men and women. This information is important to young people themselves.

Adult↗
PubMed1998

Toxicity of cytostatic drugs to normal bone marrow cells in vitro.

In this study we compared how different concentrations and periods of incubation of anthracyclines, amsacrine, and cytosine arabinoside would affect normal hematopoietic bone marrow cells in terms of interindividual differences in toxicity, the age of the donor, and the proliferative capacity of the bone marrow. Bone marrow was obtained from 36 donors in connection with bone marrow transplantation. After separation the mononuclear cell fraction was incubated with doxorubicin, 4-epidoxorubicin, daunorubicin, idarubicin, aclarubicin, mitroxantrone, amsacrine, and cytosine arabinoside for 1 h, for 3 h, or continuously. The cells were thereafter cultured in soft agar and CFU-GM were counted after 10-12 days. The results showed a large interindividual variation in toxicity for all drugs tested. Daunorubicin, idarubicin, aclarubicin, and mitoxantrone had a pronounced cytotoxic effect after 1 h of incubation. Doxorubicin and 4-epi-doxorubicin showed the greatest cytotoxic effect after 3 h and were also more toxic to normal bone marrow cells from donors over 40 years of age. Ara-C had a low cytotoxic effect after 1 and 3 h of incubation, even at high concentrations, but exerted a pronounced degree of toxicity during continuous incubation. Daunorubicin, idarubicin, and ara-C also showed increased toxicity to cell samples with a low proliferating capacity in the control. The conclusions drawn from these results are that interindividual variation, proliferation capacity, incubation conditions, and the age of the donors are factors of importance in the toxicity of drugs to normal hematopoietic bone marrow cells.

Adolescent↗
PubMed1998

Effect of cytokines on the toxicity of cytostatic drugs to normal bone marrow cells in vitro.

We evaluated in vitro how growth factors influenced the effect of cytostatic drugs on normal hematopoietic progenitor cells. Bone marrow was obtained from 15 donors for bone marrow transplantation. After separation the mononuclear fraction was incubated with granulocyte colony-stimulating factor (G-CSF) at 5 and 50 ng/ml, with granulocyte/macrophage colony-stimulating factor (GM-CSF) at 1 and 10 ng/ml, and with interleukin 3 (IL-3) at 0.5 and 5 ng/ml for 24 h prior to incubation with cytostatic drugs. These incubations were performed with 0.05 microM mitoxantrone and 0.2 microM daunorubicin for 1 h, and cells were thereafter cultured for colony-forming units--granulocyte/macrophage (CFU-GM) in soft agar for 10-12 days. Incubation with 0.05 microM cytosine arabinoside was performed continuously throughout the culture period. The proliferation of normal hematopoietic progenitor cells stimulated with GM-CSF at 10 ng/ml and with IL-3 at 5 ng/ml was significantly increased to 218% and 215% colonies, respectively, as compared with the control stimulated with conditioned medium only. Stimulation with G-CSF, on the other hand, did not induce any significantly enhanced proliferation relative to the control. Daunorubicin applied in combination with G-CSF at 5 ng/ml or with IL-3 at 0.5 ng/ml exerted a significantly higher degree of cytotoxicity on normal hematopoietic progenitor cells, resulting in 21% and 30% surviving colonies as compared with the 38% recorded for daunorubicin alone (P < 0.05). Neither G-CSF nor IL-3 at a higher concentration nor GM-CSF exerted a significantly altered degree of toxicity relative to cells incubated with daunorubicin alone. The cytotoxic effect exerted on normal hematopoietic cells by mitoxantrone or ara-C was unchanged or significantly decreased after stimulation with growth factors as compared with the effect on cells incubated with cytostatic drugs alone. We conclude that G-CSF and IL-3 augment the effect of daunorubicin on normal hematopoietic progenitor cells.

Adolescent↗