Validity of considering that early changes may act as indicators for non-genotoxic carcinogenesis.
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Animals↗
Biomedical subjects
M Chamberlain
Publications and source records attributed to M Chamberlain.
Consumer interest in alternatives to physician-centred hospital birth in Ottawa.
A survey of 1109 women who delivered in a hospital or at home in a major city in Canada was conducted. The women were asked to respond to questions concerning the type of health professional they would like to provide reproductive care. The choices they were offered were: midwife, obstetrician, general practitioner or nurse, or a combination. Respondents were also asked to identify if they had an interest in an alternative such as a birthing room, birthing centre or home birth, to hospital labour ward care. Almost 60% of women were interested in some form of midwifery care with the major emphasis placed on counselling and support. Of the women who expressed an interest in midwifery services a large number elected for that service to be shared with an obstetrician. Women who were older and had achieved a high level of education were more interested in midwifery services than other women. If given choices of a hospital labour, birthing room, birthing centre or home birth 53% of women would choose to give birth in a hospital labour ward. A major reason for this choice was the accessibility of epidural analgesia. The majority of women who had experienced a home birth would make the same choice again. There was a strong positive association between interest in using midwifery services and interest in a birthing centre and home birth.
Adolescent↗
Mapping the transcriptional transactivation function of simian virus 40 large T antigen.
T antigen is able to transactivate gene expression from the simian virus 40 (SV40) late promoter and from several other viral and cellular promoters. Neither the mechanisms of transactivation by T antigen nor the regions of T antigen required for this activity have been determined. To address the latter point, we have measured the ability of a set of SV40 large T antigen mutants to stimulate gene expression in CV-1 monkey kidney cells from the SV40 late promoter and Rous sarcoma virus (RSV) long terminal repeat (LTR) promoter. Transactivation, although reduced, was retained by an N-terminal 138-amino-acid fragment of T antigen. Mutants with alterations at various locations within the N-terminal 85 amino acids transactivated the RSV LTR promoter less well than did wild-type T antigen. Most of these were also partially defective in their ability to transactivate the SV40 late promoter. Two mutants with lesions in the DNA-binding domain that were unable to bind to SV40 DNA were completely defective for transactivation of both promoter, while a third mutant with a lesion in the DNA-binding domain which retained origin-binding activity transactivated both promoters as well as did wild-type T antigen. Only a low level of transactivation was seen with mutant T antigens which had lesions in or near the zinc finger region (amino acids 300 to 350). Mutations which caused defects in ATPase activity, host range/helper function, binding to p53, binding to the retinoblastoma susceptibility protein, or nuclear localization had little or no effect on transactivation. These results suggest that N-terminal portion of T antigen possesses an activation activity. The data are consistent with the idea that the overall conformation of T antigen is important for transactivation and that mutations in other regions that reduce or eliminate transactivation do so by altering the conformation or orientation of the N-terminal region so that its ability to interact with various targets is diminished or abolished.
Adenosine Triphosphatases↗
Interest in alternative birthplaces among women in Ottawa-Carleton.
Birthing rooms, birth centres and home birth have been proposed as alternatives to the traditional in-hospital caserooms to meet the needs of women and their families more effectively. We performed a descriptive survey to determine the level of interest of childbearing women in the Ottawa-Carleton region in these birthplaces and to examine the characteristics of women who express an interest in using them. Of the 1629 women who gave birth between July 1 and Aug. 28, 1987, 1115 (68.4%) completed a self-administered questionnaire during the pregnancy, in the early postpartum period in hospital or at home. Of the respondents 577 (53.1%) said they would choose the caseroom, 316 (29.1%) the birthing room, 165 (15.2%) the birth centre and 30 (2.8%) home birth. The women who expressed an interest in a birthplace other than the caseroom were more likely than the others to be older, married, well-educated and interested in midwifery services and to breastfeed their babies (p less than 0.05). They were also more likely to have had a low-intervention vaginal birth (p less than 0.05). The interest expressed in birthing rooms, birth centres and home birth suggests that these alternatives should be considered for inclusion in the health care system.
Adolescent↗
Intrapleural bupivacaine for early post-thoracotomy analgesia--comparison with bupivacaine intercostal block and cryofreezing.
54 patients who had posterolateral thoracotomy were prospectively studied to compare the efficacy of intrapleural bupivacaine with that of bupivacaine intercostal block and cryofreezing. Patients were randomized into three groups. The intrapleural catheter group included 16 patients who had intermittent intrapleural instillation of 20 ml of 0.25% bupivacaine for forty-eight hours postoperatively. The second group included sixteen patients who were given perioperative bupivacaine intercostal block. The third group included fifteen patients treated by cryofreezing of the intercostal nerves. Visual analogue four-hourly pain score was compared between the three groups during the first forty-eight hours postoperatively. The analgesic requirements during the first postoperative week were also assessed. There was no significant difference between the three groups in the average pain score (3.61 +/- 1.37, 3.54 +/- 1.15, and 3.33 +/- 1.47 respectively). During the first forty-eight hours postoperatively, the percentage of patients who required papaveretum in the intrapleural catheter group (56.3%) was significantly less than that in the other two groups (both 100%). The average papaveretum requirement (mg per patient) in the intrapleural catheter group (27.33 +/- 25.27) was significantly less than that in the second group (52.66 +/- 26.85) but the difference was not statistically significant from that in the third group (37.66 +/- 20.95). No complications related to the use of the intrapleural catheter or to bupivacaine toxicity were encountered. In conclusion, the technique of intermittent intrapleural bupivacaine is safe and comparable in efficacy to bupivacaine intercostal block and cryofreezing. Narcotic requirements may be reduced when this technique is used.
Adult↗
Midwifery in Ontario: a survey of interest in services.
Maternity care for women in Ontario is provided almost exclusively by physicians, the majority of whom are obstetricians. Using a self-administered questionnaire, pregnant women in one Ontario city were surveyed about their interest in midwifery care as an alternative to physician care. Although 3 percent of the women surveyed had used a midwife, 60 percent expressed an interest in midwifery care, particularly the counseling and support aspects. Over 11 percent showed an interest in complete primary midwifery care.
Attitude to Health↗
The growth of simian virus 40 (SV40) host range/adenovirus helper function mutants in an African green monkey cell line that constitutively expresses the SV40 agnoprotein.
The simian virus 40 T-antigen carboxy-terminal mutants, dlA2459 and dlA2475, are cell line and temperature dependent for growth and plaque formation in monkey kidney cells. Although these mutants did form plaques on BSC-1 cells at 37 degrees C, they were about fivefold less efficient for plaque formation than wild-type simian virus 40. These mutants did not grow in CV-1 cells and did not synthesize agnoprotein in those cells. CV-1 cells which constitutively express the agnoprotein were permissive for mutant plaque formation. However, late mRNAs, virion proteins, and progeny virion yields did not accumulate to wild-type levels during mutant infection of the agnoprotein-producing cells.
Adenoviruses, Human↗
Phase I/II study of intraventricular and intrathecal ACNU for leptomeningeal neoplasia.
A total of 27 patients with leptomeningeal neoplasia were treated with the water-soluble nitrosourea ACNU given intraventricularly or intrathecally in a phase I/II study. Patients were entered in the study if they showed evidence of either a positive CSF cytology or neurodiagnostic evidence of leptomeningeal disease, or both. Patients were evaluated for toxicity and efficacy; additionally, in 13 patients ACNU pharmacokinetic studies were carried out. A variety of tumor types were represented in the study group, including primary and metastatic CNS tumors. Toxicity was mild and included pain at the injection site (four patients), transient radicular symptoms at a short distance from the injection site (three patients), and nausea and vomiting (one patient). No myelotoxicity was seen. Of 21 patients who presented with positive cytology, 8 (38%) had a conversion from positive to negative cytology, with a range of response durations from 1 to 20+ months. Of the remaining six patients with negative cytology but other neurodiagnostic evidence of leptomeningeal disease, one patient showed an improvement seen on the myelogram and one underwent a brief reduction in CSF protein. ACNU elimination from the ventricular system is rapid, with a beta slope of 0.028 min-1 and a computed elimination constant, Ko of 13 min. The mean clearance was 3.8 ml/min (range, 1.0-6.2 ml/min). Peak ACNU levels varied between 108 and 620 micrograms/ml, with the AUC being 1.4-14.7 mg.min/ml. The total dose of ACNU given was between 9 and 104 mg, and the single dose range was 4-16.5 mg. We conclude that ACNU can be given safely with minimal toxicity as intra-CSF therapy, that it demonstrates efficacy in some patients with leptomeningeal disease, and that further studies are warranted to evaluate more fully alternative dosing and drug delivery approaches.
Arachnoid↗
Simian virus 40 host range/helper function mutations cause multiple defects in viral late gene expression.
Simian virus 40 (SV40) deletion mutants dlA2459 and dlA2475 express T antigens that lack the normal carboxy terminus. These mutants are called host range/helper function (hr/hf) mutants because they form plaques at 37 degrees C on BSC-1 and Vero monkey kidney cell lines but not on CV-1p monkey kidney cells. Wild-type SV40 can provide a helper function to permit growth of human adenoviruses in monkey kidney cells; the hr/hf mutants cannot. Progeny yields of hr/hf mutants are also cold sensitive in all cell lines tested. Patterns of viral macromolecular synthesis in three cell lines (Vero, BSC-1, and CV-1) at three temperatures (40, 37, and 32 degrees C) were examined to determine the nature of the growth defect of hr/hf mutants. Mutant viral DNA replication was similar to that of the wild type in all three cell lines, indicating that the mutations affect late events in the viral lytic cycle. In mutant-infected Vero cells, in which viral yields were highest, late mRNA levels were similar to those observed during wild-type infection. Levels of viral late mRNA from mutant-infected CV-1 and BSC-1 cells at 32 and 37 degrees C were reduced relative to those of wild-type-infected cells. The steady-state level of the major viral capsid protein, VP1, in mutant-infected CV-1 cells was reduced to the same extent as was late mRNA. The synthesis of agnoprotein could not be detected in mutant-infected CV-1 cells but was readily detected in CV-1 cells infected by wild-type SV40. Primer extension analyses indicated that most late mRNAs from mutant-infected CV-1 cells utilize start sites downstream from the major wild-type cap site (nucleotide 325) and the agnoprotein initiation codon (nucleotide 335). These results indicate that deletion of the carboxyl-terminal domain of T antigen affects viral late mRNA production, both quantitatively and qualitatively. The agnoprotein is detected late in the wild-type SV40 lytic cycle and is thought to play a role in the assembly or maturation of virions. Reduced hr/hf progeny yields could result from decreased capsid protein synthesis and, in the absence of detectable levels of agnoprotein, from inefficient use of available capsid proteins.
Amino Acid Sequence↗
Treatment of recurrent gliomas with 1,3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine.
Thirty-eight patients with primary recurrent anaplastic gliomas and glioblastomas, were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the polyamine inhibitor alpha-difluoromethylornithine (DFMO). There were 5 brain stem, 1 cerebellar, and 32 supratentorial glioma tumors. All had been treated with surgery (except in the case of 4 brain stem tumors for which biopsies were not obtained) and radiotherapy. Eight patients had received prior chemotherapy. Of the 21 patients with evaluable supratentorial anaplastic gliomas, 2 (9.5%) had a partial response and 10 (47.6%) had stable disease. The median time to tumor progression for the anaplastic gliomas has not been attained yet. However, median survival for these 12 patients was 119 weeks measured from the initiation of chemotherapy. Median survival for the entire anaplastic glioma group of 21 was 56 weeks. Minimal activity was seen against glioblastoma multiforme. The median time to tumor progression was 8 weeks with median survival of 21 weeks. Of the 5 patients with brain stem tumors, 3 are alive with stable disease at 77, 93, and 220 weeks. The combination was well tolerated with dose-limiting toxicity being myelosuppression and hearing loss. Further trials are warranted to compare the combination of BCNU and DFMO against BCNU alone in a prospective randomized trial.
Antineoplastic Combined Chemotherapy Protocols↗
Using the OSCE to measure clinical skills performance in nursing.
The measurement of clinical skills performance continues to pose a challenge for nurse educators. This paper will report on the use of the objective structured clinical examination (OSCE) to measure the psychomotor learning outcomes of a programme designed to assist students to learn to conduct a nursing neurological examination. The OSCE has a tradition in medicine, having been developed by Ronald Harden in Scotland and first reported in the British Medical Journal in 1975. The University of Ottawa has the longest North American experience with this type of evaluation procedure and there is an increasingly rich medical literature referring to the OSCE. Although the OSCE appears to be a promising method for evaluating competence in the performance of clinical skills, there are no studies in the nursing literature examining the use of the OSCE as a method for evaluating the performance of clinical skills by nurses. Our experience suggests that the OSCE may be a powerful tool in the evaluation of clinical competence in nursing and that it may also be an effective facilitator for learning to perform clinical skills in nursing.
Clinical Competence↗
The sor gene of HIV-1 is required for efficient virus transmission in vitro.
The genome of the human immunodeficiency virus HIV-1 contains at least eight genes, of which three (sor, R, and 3' orf) have no known function. In this study, the role of the sor gene was examined by constructing a series of proviral genomes of HIV-1 that either lacked the coding sequences for sor or contained point mutations in sor. Analysis of four such mutants revealed that although each clone could generate morphologically normal virus particles upon transfection, the mutant viruses were limited in their capacity to establish stable infection. Virus derived from transfection of Cos-1 cells (OKT4-) with sor mutant proviral DNA's was resistant to transmission to OKT4+ "susceptible" cells under cell-free conditions, and was transmitted poorly by coculture. In contrast, virus derived from clones with an intact sor frame was readily propagated by either approach. Normal amounts of gag-, env-, and pol-derived proteins were produced by all four mutants and assays in both lymphoid and nonlymphoid cells indicated that their trans-activating capacity was intact and comparable with wild type. Thus the sor gene, although not absolutely required in HIV virion formation, influences virus transmission in vitro and is crucial in the efficient generation of infectious virus. The data also suggest that sor influences virus replication at a novel, post-translational stage and that its action is independent of the regulatory genes tat and trs.
Animals↗
Phase II study of combined carmustine, 5-fluorouracil, hydroxyurea, and 6-mercaptopurine (BFHM) for the treatment of malignant gliomas.
The Neuro-oncology Service of the University of California Brain Tumor Research Center conducted a nonrandomized phase II study to evaluate, in patients with recurrent malignant glioma, the benefit of a four-drug combination (BFHM) consisting of carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea), 5-fluorouracil, hydroxyurea, and 6-mercaptopurine. There were 29 evaluable glioblastoma multiforme patients and 45 nonglioblastoma anaplastic glioma patients available for analysis. Tumor progression was analyzed as the primary study endpoint. Of the glioblastoma patients, 16 of 29 (55%) responded or stabilized on therapy; of the other anaplastic gliomas, 32 of 45 (71%) responded or stabilized. For patients who stabilized or responded to treatment, BFHM achieved a median time to tumor progression of 46 weeks with a 25th percentile time to tumor progression of 68 weeks for anaplastic gliomas and a median time to tumor progression of 23 weeks with a 25th percentile time to tumor progression of 36 weeks for glioblastoma multiforme patients. A Cox multivariate analysis demonstrated that age and Karnofsky score were important prognostic variables for these patients.
Adolescent↗
The effect and mode of action of zinc pyrithione on cell growth. I. In vitro studies.
The effects of zinc pyrithione (ZnPTO) were studied in a series of in vitro tests to determine whether its mode of action is primarily cytostatic or cytotoxic. Sodium pyrithione (NaPTO) was also studied, to check that pyrithione was the active moiety, and the known cytostatic chemical hydroxyurea was included for comparison. ZnPTO had a reversible inhibitory effect on the growth of BHK 21 cells at 0.1 microgram/ml, but had a rapid, irreversible inhibitory effect at 1 microgram/ml associated with cell rounding and detachment. NaPTO produced a similar effect but hydroxyurea produced an essentially reversible inhibition even at a dose well above that producing complete inhibition. ZnPTO and NaPTO both caused contraction, rounding and blebbing of BHK 21 cells in perfusion-chamber tests, at higher levels (1 and 10 micrograms/ml) than required for growth inhibition, but only 10 micrograms ZnPTO/ml caused lactate dehydrogenase (LDH) release. Hydroxyurea had no effects in these tests. ZnPTO and NaPTO also reduced the survival of Chinese hamster V79 cells sharply over a narrow dose range (0.01-0.03 microgram/ml), but the effect of hydroxyurea was not as sharp and occurred at much higher doses. All three showed elements of cytostasis and cytotoxicity as demonstrated by analysis of the relationship between survival and colony area. Of the three, only ZnPTO (at greater than or equal to 5 micrograms/ml) caused significant LDH release from the cells, though both ZnPTO and NaPTO (at 0.1-1 microgram/ml) inhibited cell growth as indicated by total LDH values. In studies with rat peritoneal mast cells, ZnPTO and NaPTO (at 10 ng/ml) both suppressed histamine release induced by 48/80 or Ca ionophore A23187, though neither caused histamine release directly. The combined results of these tests show that ZnPTO is primarily cytotoxic, rather than cytostatic.
Animals↗
Radioaerosol ventilation imaging in ventilator-dependent patients. Technical considerations.
The differentiation of pulmonary embolism (PE) from regional ventilatory abnormalities accompanied by reduced perfusion requires contemporary perfusion and ventilation studies. Distinguishing these conditions in ventilator-dependent patients is aided by administering a Tc-99m aerosol to characterize regional ventilation, and by performing a conventional Tc-99m MAA perfusion study. The technique uses a simple "in-house" constructed apparatus. Simple photographic techniques suffice, but computer subtraction of perfusion from the combined perfusion-ventilation image renders interpretation easier if aerosol administration follows perfusion imaging. Multiple defects can be examined in a single study. Excluding normal or near-normal perfusion studies, PE was thought to be present in eight of 16 patients after perfusion imaging alone, but in only one of eight after added aerosol imaging. Angiography confirmed the diagnosis in that patient. Of the eight patients who had abnormal perfusion but were thought unlikely to have PE from the perfusion study alone, two had normal ventilation, and subsequently were shown to have PE by angiography. Because angiography was only performed on patients who were thought to have a high probability of PE on sequential perfusion-ventilation imaging, the true incidence of PE may have been higher. Aerosol ventilation imaging is a useful adjunct to perfusion imaging in patients on ventilators. It requires an efficient delivery system, particularly if aerosol administration follows perfusion imaging, as it does in this study. The major disadvantage of aerosol imaging compared to a gas in intubated patients is the significant bronchial deposition due to retained mucus secretions.(ABSTRACT TRUNCATED AT 250 WORDS)
Aerosols↗
Protective vaccination against virulent Babesia bovis with a low-molecular-weight antigen.
A Babesia bovis low-molecular-weight antigen was purified from crude material by using affinity adsorption techniques first with a mouse monoclonal antibody and then by adsorption with normal bovine sera. The antigen was then further purified by gradient gel electrophoresis. Analysis by Western transfer revealed only one antigen band, with an apparent molecular mass of 29 kilodaltons. A band (12 by 0.3 by 0.6 cm) corresponding to this antigen was excised from the acrylamide gel and injected twice 4 weeks apart, together with 2.5 ml of Freund complete adjuvant, into nine nonsplenectomized adult cattle. The vaccinated cattle and five susceptible control animals were challenged with a virulent homologous strain 4 weeks after the second vaccination. None of the vaccinated animals was clinically affected, whereas three of five controls were severely affected. Control animals had significantly greater declines in packed cell volume and greater rises in temperature and parasitaemias than vaccinated animals.
Animals↗
Cytotoxic action of mineral dusts on CHV 79 cells in vitro: factors affecting toxicity.
The cytotoxic action of a series of mineral dusts has been studied using Chinese hamster V79-4 cells obtained from three separate laboratories in the UK. The dusts which have been studied include samples of asbestos from the Union Internationale Contre le Cancer reference series and an internationally available sample of quartz (DQ12). Besides comparing results obtained with the three different cells, two alternative methods of exposing the cells to the dusts were also compared. The toxicity assay employed uses the inhibition of colony formation from a single cell suspension as a measure of toxicity. The numbers of colonies which grow in the presence of the various concentrations of the dusts are expressed as percentages of the colonies which grow in the untreated control cultures. The absolute toxicity of a dust was found to depend principally on the method of exposing the cells to the dust. However, differences in the relative toxicities of the dusts depended on the source of the cells. The implications of these results for experiments in which Chinese hamster V79-4 cells are used in in vitro test systems to assess the potential pathogenicity of mineral dusts are discussed.
Animals↗
Effect of mineral dusts on metabolic cooperation between Chinese hamster V79 cells in vitro.
The mode of action of inorganic fibers as carcinogens is unknown. There is conflicting evidence whether they act by inducing lesions in DNA, such as initiating carcinogens, or alternatively act as promoters of carcinogenesis. Recent evidence has suggested that promoters inhibit the process of cell-to-cell chemical communication known as metabolic cooperation. Chinese hamster V79-4 cells in culture exhibit metabolic cooperation which can be blocked by the promoter tetraphorbol-13-acetate (TPA). Three kinds of mineral dust were tested to determine whether or not they could interfere with the intercellular communication. The three dusts studied were: amosite, a fibrous asbestos from the Union Internationale Contre le Cancer (UICC) standard reference series, which is a typical carcinogenic fibrous dust inducing pleural tumors following intrapleural injection into rats; ball-milled amosite, a nonfibrous dust derived from UICC amosite by ball-milling, which has the physical properties characteristic of a noncarcinogenic dust; and Min-U-Sil silica, a widely available sample of fibrogenic quartz which does not induce pleural tumors following intrapleural injection into rats. The results demonstrated that metabolic cooperation between V79-4 cells cannot be reduced by carcinogenic asbestos fibers or by relatively large numbers of nontoxic dust particles. It is concluded that if inorganic fibers promote carcinogenesis, then they do not operate by blocking metabolic cooperation.
Animals↗