Search PubMed⌕ Search

Biomedical subjects

C Paul

Publications and source records attributed to C Paul.

At least 199 records · Page 11Linked to original sources
PubMed1993

Synthesis of 2-deoxy-D-galactose containing gangliosides in vivo.

Incorporation of 2-deoxy-D-galactose into the oligosaccharide moieties of different gangliosides of rat liver was examined. After intraperitoneal administration of 2-deoxy-D-galactose it was shown by GLC/MS analysis that this hexose analogue is metabolized and incorporated into all the gangliosides investigated, and predominantly into GM3 and GD3. In both of these gangliosides, 25-55% of the galactose residues were substituted by 2-deoxy-D-galactose. The epimer, 2-deoxy-D-glucose, was not detectable.

Animals↗
PubMed1993

HLA-DP/DR interaction in early onset pauciarticular juvenile chronic arthritis.

We investigated the polymorphic second exon of the HLA-DPB1 and HLA-DRB1 genes, using in vitro DNA amplification by polymerase chain reaction (PCR) and oligonucleotide hybridization in 136 patients with early onset pauciarticular juvenile chronic arthritis (EOPA-JCA) and 199 healthy controls. The analysis of the HLA-DRB1 system revealed that most of the DRB1 alleles are not indifferent with respect to susceptibility to EOPA-JCA. There is a hierarchy of susceptible (DRB1*08, DR5), "permissive" (DRB1*01), moderately "protective" (DR2, DRB1*04), and "protective" (DRB1*07) alleles. In contrast, no hierarchy could be shown for the HLA-DPB1 system. DPB1*0201 was found to be susceptible. The relatively frequent alleles DPB1*0402 and DPB1*0401 seem to be indifferent. The associations with DPB1*0201, DR5, and DRB1*08 are independent of each other: that is to say they, are not brought about by linkage disequilibrium. The susceptible alleles DPB1*0201 and DR5 show evidence for interaction in the pathogenesis of EOPA-JCA. Interaction seems likely between DPB1*0201 and DRB1*08, DR5 and DRB1*08, or between DR6 and DRB1*08. The strongest interaction exists between DPB1*0201 and a common DQ factor associated with both DR5 and DRB1*08. Finally, we observed a hierarchy among the various marker combinations, where the risk of developing EOPA-JCA increases with the number of associated markers present in an individual.

Alleles↗
PubMed1993

A national study to monitor the safety of IUCD use.

OBJECTIVE: To determine whether the known adverse effects of IUD use were being kept to a minimum in a population of women. DESIGN: A national survey of all doctors purchasing IUDs in a three-month period. Information was sought on the doctors' training, experience and usual insertion practice, and also on characteristics of each woman receiving an IUD in the study period. MAIN OUTCOME MEASURES: Published national and international guidelines on selection of users for IUDs and on training for IUD insertion were compared with our findings on these measures. RESULTS: Not all IUD insertions were in accordance with published guidelines. Very few IUD insertions (0.9%) were carried out in the face of absolute contraindications to this type of contraception. However, 126 insertions (27%) were for women who had a relative contraindication, excluding an incomplete family. Gynaecologists were significantly less likely to fit an IUD in the presence of contraindications than other doctors. Few doctors reported training to the standard recommended. CONCLUSIONS: That the known adverse effects of IUD use are not being kept to a minimum for New Zealand women. The study design could be used to estimate the potential for adverse effects in populations for other types of contraceptives.

Adolescent↗
PubMed1993

Comparison of a bioluminescence assay with differential staining cytotoxicity for cytostatic drug testing in vitro in human leukemic cells.

An ATP assay using bioluminescence was evaluated for its ability in determining the cytotoxic effect of antileukemic drugs. Leukemic cells from 32 patients with ANLL were used to compare the ATP assay with the differential staining cytotoxicity assay (DiSC). Cells were incubated with doxorubicin, daunorubicin, idarubicin, mitoxantrone and ara-C in conditions that were adapted to mimic the in vivo exposure of leukemic cells to cytostatic drugs. After incubation the cells were cultured in liquid medium for 4 days and then analyzed for ATP content using the firefly luciferase method in an automated procedure. The cytotoxic effect as measured by both methods correlated satisfactorily (r = 0.8). We conclude that the automated ATP assay can replace the more time consuming DiSC assay for in vitro drug testing in ANLL.

Adenosine Triphosphate↗
PubMed1993

Intracellular concentrations of mitoxantrone in leukemic cells in vitro vs in vivo.

The aim of this study was to determine the intracellular pharmacokinetics of mitoxantrone in vivo and to use these results to establish how leukemic cells should be incubated to perform clinically relevant in vitro studies of this drug. Blood samples were obtained from 11 patients with acute nonlymphoblastic leukemia at certain intervals up to 20 h after the infusion of mitoxantrone 12 mg/m2. Plasma and leukemic cells were separated and the drug concentrations were determined with HPLC. Before treatment, leukemic cells from 12 patients were incubated with 0.02, 0.05, 0.1, 0.2 and 1.0 microM mitoxantrone for 1-4 h and thereafter cultured in suspension culture for 20 h; during this time cell samples were taken at certain intervals for drug determination. In cells incubated with 0.05 and 0.2 microM mitoxantrone the cytotoxic effect was measured with the DiSC assay after cultivation for 4-5 days. In vivo, the intracellular levels exceeded the plasma concentrations already at the end of infusion and after 2 h the intracellular concentrations were 200-300 times higher than in plasma. In vitro, the intracellular steady state level of mitoxantrone was reached after 1-2 h and there was a pronounced intracellular retention even after 20 h culture in drug-free medium. Incubation with 0.05 microM during 1 h gave intracellular concentrations of mitoxantrone similar to those achieved in vivo. This incubation concentration gave a mean cytotoxic effect of 53% living cells measured with the DiSC assay, which gives good possibilities to discriminate between mitoxantrone-sensitive and unsensitive cells. We believe that exposing leukemic cells in vitro for in vivo mimicking mitoxantrone concentrations could increase the clinical relevance of predictive assays.

Adult↗
PubMed1993

Infection due to Klebsiella rhinoscleromatis in two patients infected with human immunodeficiency virus.

Two cases of rhinoscleroma in patients infected with the human immunodeficiency virus (HIV) who had stayed in an area of endemic Klebsiella rhinoscleromatis are reported. One of the patients presented with oropharyngeal lesions, an unusual clinical picture. Both patients suffered from a major cellular immune deficiency. The importance of Klebsiella rhinoscleromatis infection in AIDS-related oropharyngeal pathology and the possible treatment of such infection in HIV-positive patients are not yet clearly established.

AIDS-Related Opportunistic Infections↗
PubMed1993

Retrospective analysis of platelet numbers and volumes in normal pregnancy and in pre-eclampsia.

OBJECTIVE: To determine the distribution of platelet volumes and numbers through pregnancy, and to compare these to changes in platelet volumes and numbers in women with pre-eclampsia. SUBJECTS: Four hundred twenty-eight women with normal pregnancy from whom four or more platelet measurements were available were identified. 74 women with pre-eclampsia (blood pressure > or = 140/90 mmHg, at least 0.5 g protein/24 h urine collection) from whom platelet measurements were available between 27 and 30 weeks of gestation were identified. RESULTS: Mean platelet volume and platelet number remained constant in normal pregnancies between the first trimester and the end of pregnancy. A persistent increase of > or = 0.8 fl (> or = 90th centile) in mean platelet volume was found in 14 out of 15 pre-eclamptic patients between 24 weeks and 38 weeks of gestation and in only 13 of 428 normal pregnant individuals. Platelet numbers were decreased by > or = 50 x 10(9)/l (i.e. to less than the 10th centile) in 12 of the 15 patients with pre-eclampsia. 10% of the normal pregnant population showed a similar decline in platelet numbers showing that changes in platelet numbers may be a less accurate assessment of the development of pre-eclampsia. CONCLUSION: We suggest that longitudinal determination of platelet volumes may be of use in identifying those women at risk of pre-eclampsia.

Adolescent↗
PubMed1993

A retrospective analysis of bleeding complications in 438 patients with acute leukaemia during the years 1972-1991.

The incidence and mortality of bleeding complications have been investigated in 438 patients with acute leukaemia consolidated either by chemotherapy (n = 241) or by bone marrow transplantation (n = 197). Bleeding signs on admission were found in 38% of the chemotherapy-treated group. Haemorrhagic deaths during the 1st month were seen in 10%. The majority of the major bleedings were localized intracranial, but gastrointestinal haemorrhages were also common. The platelet count was significantly lower (40 x 10(9)/l versus 69 x 10(9)/l, p < 0.001) and the leukocyte count significantly higher (31.2 x 10(9)/l versus 11.6 x 10(9)/l, p < 0.001) in the group with bleeding complications than in those without. The haemorrhagic mortality in patients consolidated with chemotherapy compared with transplant patients was similar, 23% and 19%. The majority of the lethal haemorrhages in the latter group were observed in patients undergoing allogenic bone marrow transplantation after engraftment. Septicaemia, graft-versus-host and venous occlusive disease were contributing factors.

Acute Disease↗
PubMed1993

DNA typing for HLA-DPB1-alleles in German patients with systemic lupus erythematosus using the polymerase chain reaction and DIG-ddUTP-labelled oligonucleotide probes. Members of SLE Study Group.

Genomic DNA of 178 German Caucasian patients with systemic lupus erythematosus are studied for HLA-DP locus by using PCR and DIG-ddUTP-labelled oligonucleotide probes. A significant increase of DPB1*0101 is observed in SLE patients compared with healthy controls (chi 2 = 15.27, p.c. < 0.004). DPB1*0501 and *0901 are also slightly increased (chi 2 = 5.85, P < 0.05, p.c. = NS; chi 2 = 5.64, P < 0.05, p.c. = NS). There is no significant difference in frequency of DP alleles between male and female patients. Since a linkage disequilibrium between HLA-B, DR and DP loci is found in our SLE patients, an analysis is performed assessing the relative importance of these HLA-markers to SLE. The results show that the increase of DPB1*0101 in SLE patients is associated with the HLA-B8, DR3 haplotype and it suggests a more important role for HLA-B8, DR3 or genes within this haplotype than for DPB1*0101 in the genetic predisposition for SLE.

Alleles↗
PubMed1993

Polymorphism of the 5' flanking region of the HLA-DQA1 gene in coeliac disease.

Coeliac disease (CD) is associated with particular HLA genotypes. The susceptibility gene (or genes) has been mapped to the class II region, most probably to the DQ loci. Polymorphism of the upstream promoter region of the DQA1 gene (QAP) has been recently reported. At least ten variants or QAP alleles have been found, some of which are present in the cis-acting regulatory sequences. Allelic differences in DQ molecule expression may play a role in susceptibility to CD. We investigated the QAP polymorphism in 102 CD patients and 142 unrelated healthy controls of Czech origin using polymerase chain reaction amplification (PCR) of genomic DNA and oligonucleotide probes. We found a significant frequency increase of the alleles QAP 4.1 (RR = 10.3, p.c. = 10(-6) and QAP 2.1 (RR = 2.4, p.c. = 0.017) in patients over controls. An increased susceptibility is provided by the presence of both alleles, as is shown by the higher proportion of QAP 4.1, 2.1 heterozygotes among patients than expected from the Hardy-Weinberg equilibrium and by the comparison of the odds ratios for these alleles. There is a strong linkage disequilibrium between the QAP alleles and the DQA1, DQB1, and DRB1 loci. Two haplotypes carrying the QAP alleles whose frequency is increased are predominant in this group of CD patients: DQB1*0201, DQA1*0501, QAP4.1, DRB1*0301 and DQB1*0201, DQA1*0201, QAP 2.1, DRB1* 0701. Thus, the QAP variants are increased as part of these haplotypes and we cannot discriminate if they are responsible for the primary association.

Alleles↗
PubMed1993

Adolescents, sexual behaviour and implications for an epidemic of HIV/AIDS among the young.

OBJECTIVE: To determine the patterns of sexual behaviour, condom use and sexually transmitted diseases among young New Zealanders, and the characteristics of those with many sexual partners. SUBJECTS: A cohort of young people enrolled in a longitudinal cohort study, and followed up since age three. METHODS: Subjects were interviewed at age 18 years as part of a multidisciplinary health and development study. Questions about sexual behaviour were presented by computer. RESULTS: Overall 862/1027 (83.9%) surviving in the cohort was interviewed. Only 1.4% declined to answer the section on sexual behaviour. Sexual intercourse in the previous 12 months was reported by 57.6% of the young men and 67.9% of the young women. Amongst those who were sexually active more of the young men reported multiple partners than the young women (59.8% v 46.5% p < 0.001). There was a trend for increasing number of partners with indices of lower school achievement but no significant association with socio-economic status. Condom use decreased with increasing number of partners for the young women, and for the young men there was no association. Sexually transmitted diseases were reported more commonly with increasing number of sexual partners for both men and women. The rates of sexual activity were substantially higher than reported in a comparable survey 20 years ago. CONCLUSIONS: The pattern of sexual behaviour and condom use, and the occurrence of sexually transmitted diseases in this sample give cause for concern about the spread of sexually transmitted diseases including the possibility of an epidemic of HIV among heterosexual young people in New Zealand. The findings should help in targeting health promotional activities within this age group.

Acquired Immunodeficiency Syndrome↗