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Confidentiality↗
Biomedical subjects
C Paul
Publications and source records attributed to C Paul.
Expression of glutathione transferase pi as a predictor for treatment results at different stages of acute nonlymphoblastic leukemia.
The expression of glutathione transferase pi (GST pi) was studied in leukemic cells from 60 patients with acute nonlymphoblastic leukemia at diagnosis and at progressing stages of the disease. A polyclonal rabbit antibody to human placental GST pi coupled with peroxidase antiperoxidase staining was used for immunodetection of GST pi on sections of routinely fixed bone marrow clots. All patients had received induction therapy based on an anthracycline and a standard dose of ara-C. The expression of GST pi at diagnosis was significantly correlated with response to induction therapy, duration of first remission, and overall survival. Twenty-nine of 36 samples of bone marrow from patients that entered complete remission (CR) following primary induction therapy showed a low expression, whereas nine of 16 sections from patients with resistant disease showed a high expression of GST pi (P less than or equal to 0.03). Of 40 sections that showed a low expression of GST pi, 29 (73%) were taken from patients that achieved a CR, whereas 12 of 19 sections that showed a high expression of the enzyme were from patients with resistant disease or that entered CR only after additional therapy (P less than or equal to 0.02). The median duration of first CR was 18.2 mo for patients whose cells showed a low expression of GST pi compared with 6.7 mo for those that entered CR in spite of a high expression of the enzyme (P less than or equal to 0.005). Of cells from ten patients that at the time of study were in a continuous first CR, none expressed high concentrations of GST pi. The expression of GST pi remained rather constant in most patients as the disease progressed to clinical resistance. At relapse there was no significant correlation between the expression of GST pi and treatment results but, of ten patients that entered a second CR or achieved a partial remission, only one showed a high expression of the enzyme. We conclude that there was a significant correlation between the expression of GST pi at the time of diagnosis and the subsequent treatment results and that GST pi is a useful marker for clinical resistance to cytostatic drugs in acute nonlymphoblastic leukemia.
Adolescent↗
Incorporation of N-acyl-2-amino-2-deoxy-hexoses into glycosphingolipids of the pheochromocytoma cell line PC 12.
The synthesis of N-acyl-2-amino-2-deoxy-hexoses, their metabolism and their incorporation into glycosphingolipids of rat pheochromocytoma cell line PC 12 were investigated. The data indicate that in PC 12 cells the N-acyl-2-amino-2-deoxy-hexoses, N-propanoyl-D-glucosamine and N-butanoyl-D-glucosamine are metabolized to the corresponding phosphates, and that N-propanoyl-D-glucosamine is also metabolized to N-propanoyl neuraminic acid. Using variously radiolabelled N-acyl-2-amino-2-deoxy-hexoses, their incorporation into glycosphingolipids was shown.
Animals↗
Incorporation of the hexose analogue 2-deoxy-D-galactose into membrane glycoproteins in HepG2 cells.
The incorporation of 2-deoxy-D-galactose into the oligosaccharide moieties of glycoproteins and the consequences of 2-deoxy-D-galactose treatment on the fucosylation of glycoproteins were investigated in the human hepatoma cell line HepG2. Using different methods, it was shown that treatment of HepG2 cells with 2-deoxy-D-galactose leads to an incorporation of 2-deoxy-D-galactose and a decrease of L-fucose incorporation into the oligosaccharides of glycoproteins. The extent of labeling by L-[3H]fucose was determined by removing L-[3H]fucose from labeled cells with the aid of a purified alpha 1,2-fucosidase from Aspergillus niger. Using this method, it was shown that 2-deoxy-D-galactose markedly inhibits alpha 1,2-fucosylation. Measurement of the amount of 2-deoxy-D-galactose incorporated, however, showed that replacement of D-galactose by 2-deoxy-D-galactose does not entirely account for the decrease in alpha 1,2-fucosylation. In addition, a hitherto unreported compensatory increase of alpha 1,3/alpha 1,4-fucosylation was found to occur when alpha-1,2-fucosylation was inhibited by treatment with 2-deoxy-D-galactose.
Adenosine Triphosphate↗
Bleeding complications and coagulopathy in acute leukaemia.
Factors and inhibitors of coagulation and fibrinolysis were investigated on admission in 57 patients with acute leukaemia and they were correlated to the occurrence of haemorrhage. Coagulation disturbances were found in 98%. Seventeen of the patients with haemorrhagic symptoms had major bleeding. Severe thrombocytopenia (< 20 x 10(9)/l) was found in 16%. Patients with major bleedings had significantly lower concentrations of prothrombin complex, fibrinogen, protein C and platelets. Low levels of antiplasmin and fibrinogen were characteristic of 'bleeders' with promyelocytic and lymphoblastic leukaemia. We found a positive correlation between vWF:Ag and leukaemic cell count especially in lymphoblastic leukaemia (ks = 0.72). Reduced levels of antithrombin indicated a poorer prognosis.
Acute Disease↗
Elastase activity in leukaemic cells and plasma in patients with acute leukaemia.
Proteolysis of coagulation factors and inhibitors resulting in haemorrhage can be mediated by elastase. Indirect signs of this are elevated levels of elastase complexed to its inhibitor in plasma, alpha 1-antitrypsin (E alpha 1-AT). We have measured intracellular elastase activity in leukaemic cells from 60 patients with acute leukaemia. Elastase activity was detected in 92% of the patients with acute nonlymphoblastic leukaemia (ANL), no activity was found in the patients with acute lymphoblastic leukaemia (ALL). High levels were found in cells from patients with promyelocytic leukaemia. Moderate to high total circulating blast elastase activity was measured in 70% of the ANL patients with haemorrhage compared with 36% of the patients without bleeding complications (p < 0.05). The available intracellular elastase activity was correlated to the level of E alpha 1-AT (rs = 0.42, p < 0.01) but not to the elastase specific split product of fibrinogen, B beta 30-43. In complete remission the levels of E alpha 1-AT were normalized. Intracellular elastase activity might be a useful supplement to differentiate ANL and ALL.
Adolescent↗
Preventive health behaviours among parents of infants aged four months.
Six preventive health behaviours have been frequently identified as having the potential to reduce mortality and morbidity during infancy: breast-feeding until the age of six months; no solid food until after four months of age; immunisation against whooping cough, diphtheria, poliomyelitis and tetanus; the use of a baby capsule to restrain the infant when travelling in a motor vehicle; regular attendance at a health care provider for preventive health checks; and no maternal smoking. This study surveyed 191 primiparous women four months after the birth of their babies to explore the proportion of parents who perform the recommended preventive health behaviours and the association among the behaviours. Thirty-nine per cent of the women reported that they were no longer breast-feeding by the time their infant was four months old; 35 per cent had introduced solids before 16 weeks of age; 35 per cent did not always use a baby capsule when travelling with their baby in their car, 25 per cent did not regularly attend the early childhood health centres and 22 per cent smoked. Forty-eight per cent of the sample were performing four or fewer of the six preventive health behaviours and 21 per cent were performing three or fewer. The relationship between performing each preventive health behaviour and a range of demographic variables was investigated. A logistic regression indicated that performing three or fewer of the health behaviours was associated with lower levels of education, having public health insurance and being born in a country other than Australia.
Adult↗
Elastase activity in leukemic cells.
Elastase, a proteolytic enzyme which digests different clotting factors, has previously been isolated from monocytes, macrophages and granulocytes. In the present work, we have isolated leukemic cells from 1 patient with acute lymphoblastic leukemia (ALL) and from 6 patients with acute nonlymphoblastic leukemia. Detectable elastase activity was found in the cells from all patients with acute nonlymphoblastic leukemia and ranged from 0.016 to 0.619 mukat/l/micrograms DNA. The highest elastase activity was found in 1 patient with promyelocytic leukemia (M3), and no activity was found in the cells from the patient with ALL. It is possible that elastase-mediated proteolysis of coagulation factors is the mechanism responsible for bleeding complications which are frequent in M3.
Bone Marrow↗
[Erythroderma induced by teicoplanin].
We report the case of a 38-year old man who developed erythroderma during treatment with teicoplanin for staphylococcal septicaemia. The clinical symptoms, which included high fever, shock and erythroderma, were suggestive of staphylococcal toxic shock. After teicoplanin was withdrawn and replaced by vancomycin the disease followed a favourable course. The reintroduction test was positive. This case illustrates the problems associated with the diagnosis of erythroderma in intensive care patients and confirms that it is possible to prescribe vancomycin in cases with allergic reaction to teicoplanin.
Adult↗
DNA as a carrier for anthracyclines in the treatment of acute myelocytic leukemia (AML).
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Adolescent↗
The extent of cervical screening in New Zealand women.
To estimate the extent of cervical screening coverage of New Zealand women, a national survey of 1000 randomly selected women with a supplement of 200 Maori women was carried out by the National Research Bureau in August 1990 for the Department of Health. The results indicate a high level of screening in women aged 20-64 and improvements in coverage over the last three years, probably in response to the Cartwright inquiry. Overall, 77% of women reported having had a smear test within the previous three years and after adjustment for hysterectomy, this proportion increased to 82%. Screening coverage, however, was unevenly spread according to ethnic group, age and household income. Only 15% of European women reported no smear test in the last three years compared with 27% of Maori and Pacific Island women. The likelihood of having had a smear test in the last three years increased with increasing income. The survey confirms a high level of very frequent screening throughout New Zealand (2.4 smear tests per woman in the previous three years); the most frequent screening occurred in women 20-24 years of age (2.9 smears). Because an organised national screening programme has the potential to maintain and extend screening coverage to all age and ethnic groups, as well as reduce the number of unnecessary smears, it is likely to be more cost effective than the current screening practice.
Adolescent↗
Alcohol consumption and risk of breast cancer.
In a national case-control study, 891 New Zealand women aged 25 to 54 with newly diagnosed breast cancer were compared with 1,864 control subjects selected at random from the electoral rolls. The relative risk of breast cancer for current drinkers of alcohol, compared with women who had never drunk alcohol, was 1.0 (95% confidence interval 0.64 to 1.7). For ex-drinkers the relative risk was 1.3 (95% confidence interval 0.74 to 2.5). Women drinking up to 14 drinks per week had no increase in risk, while the relative risk in those consuming more than 14 drinks per week was 1.8 (95% confidence interval 0.87 to 3.8). There was no evidence of effect modification by age at diagnosis, menopausal status, body mass index, or any of the other variables examined. While these results provide little support for the hypothesis that moderate alcohol consumption increases the risk of breast cancer, they are not inconsistent with the weak associations that have been found in many other studies. Possible explanations for such a relationship are considered.
Adult↗
1991 cervical screening recommendations: a working group report.
The Department of Health and the Cancer Society invited a working group to review the 1985 recommendations on cervical screening. Minor modifications have been made to the earlier recommendations in the light of more information about the effectiveness of different screening policies, and in the expectation that comprehensive cytology registers to ensure recall and follow up of abnormalities will be in place shortly. All women from the age of 20 up to 70 years should be offered cervical screening every three years. Any woman who has never had sexual intercourse or who has had a hysterectomy with complete removal of the cervical epithelium for a benign condition need not be screened. Women should have a second smear within one year if they have never had a smear before or if more than five years have passed since their last smear. But recall through the register should not be more frequently than three yearly for women with a history of normal smears.
Adult↗
Occurrence of AIDS in New Zealand: the first seven years. MRC AIDS Epidemiology Group.
The 179 people in New Zealand with AIDS diagnosed up to the end of 1989 and notified by 30 June 1990 are reviewed. Retrospective data collection provided the first available information on date of diagnosis, ethnic affiliation, district of usual residence, and survival. Of the 179 people with AIDS, 173 were male. AIDS occurred most commonly between the ages of 30 and 50, but there were two children under 10. The standardised cumulative incidence rates (per 100,000) in the European, Maori, and Pacific Island populations were 5.3, 4.5, and 5.5, respectively. The majority affected (154) were men who had had sexual contact with men. Three of five intravenous drug users also reported such contact. Smaller numbers were presumed to have been infected through heterosexual contact (7), treatment of haemophilia (3), blood transfusions (2), or perinatally (1). In seven cases the mode of transmission was unknown. The proportion of people who had been living overseas when first diagnosed was initially high but declined, so that 134 were known to have been diagnosed in New Zealand. Of these, 107 lived in Auckland or Wellington. Survival analysis using the Kaplan-Meier method showed that the median time from diagnosis to death was 58 weeks.
Acquired Immunodeficiency Syndrome↗
Projections of AIDS incidence in New Zealand.
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Acquired Immunodeficiency Syndrome↗
Myocardial toxicity of high-dose cyclophosphamide in rabbits treated with daunorubicin.
The present study was performed to evaluate experimentally the possible cardiotoxicity of high doses of cyclophosphamide after pretreatment with anthracyclines, a regimen used prior to bone marrow transplantation. A total of 27 rabbits received daunorubicin at a dose of 2.25 mg/kg per week for 10 weeks. At 1 week after the last daunorubicin dose, 13 of these rabbits received cyclophosphamide at 100 mg/kg per day x2 (total dose, 200 mg/kg). All animals were killed after 1 additional week. Seven rabbits received cyclophosphamide at 100 mg/kg per day x2 and two animals were given 50 mg/kg per day x2 without additional treatment. In all, 18 untreated rabbits served as controls. At 3 h before the animals were killed, they received [99mTc]-pyrophosphate i.v. Myocardial isotope activity was determined using a detector, and cardiac specimens were examined with a gamma-camera. Cardiotoxic effects were evaluated by myocardial isotope accumulation and pathologic changes were determined by morphology and by light and electron microscopy. The pathologic evaluation showed more frequent and widespread acute myocyte necrosis in daunorubicin/cyclophosphamide-treated rabbits as compared with those treated with daunorubicin or cyclophosphamide only. Myocardial isotope accumulation in rabbits treated with daunorubicin/cyclophosphamide was significantly higher then that in animals treated with either drug alone (2 alpha less than or equal to 0.001). Rabbits receiving cyclophosphamide as a single agent showed minor myocyte lesions but did not differ from controls in terms of isotope accumulation. We conclude that high-dose cyclophosphamide treatment on a dose schedule similar to that used prior to bone marrow transplantation and given soon after long-term daunorubicin therapy is considerably cardiotoxic.
Animals↗