Injection of tubal ectopic pregnancy.
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Biomedical subjects
Publications and source records attributed to E V Mackay.
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The hypothesis that in vitro chemosensitivity testing could predict clinical outcome was tested in women with ovarian cancer. Short-term drug effects on DNA and RNA metabolism (by inhibition of 3H-thymidine and 3H-uridine incorporation) were measured in primary cultures of tumor cells. In vitro inhibitory effects were found with the four drugs tested: cisplatin, adriamycin, melphalan, and methotrexate. From data based on impaired RNA and/or DNA metabolism (greater than or equal to 20% inhibition), correct prediction of "sensitivity" was 79% and that of "resistance" was 84%. An analysis of the predictive value of both assays, used singly or together, revealed a high specificity but moderate sensitivity; the best positive predictive value (94%) was obtained when both RNA and DNA metabolisms were impaired. Our results support the idea that two subsets of patients who are being considered for cytotoxic chemotherapy can be selected; those who may benefit from treatment and those who may not, regardless of the drugs tested in vitro or used in vivo.
Tumor sensitivity of ovarian cancer to cytotoxic drugs in vitro was examined between paired samples taken from the primary tumor and its metastases in the same patient. A 3-hour assay of primary cultures of the tumor was used to determine cellular response to the drugs by measurement of the incorporation of [3H]thymidine. Although there was variability, a reasonable correlation was found between the primary tumor and its different metastases, between the different metastases, and between the different tumor sites and cells from the peritoneal fluid. However, there was discordance between some of the pairings; the rate varied between 12 and 42% when the criterion was greater than 20% inhibition. Consistent drug sensitivity for all sites tested was present in only 8 of the 18 patients. Because of the discordance in some pairings, attempts should be made to sample all metastatic tumors, particularly those which cannot be removed completely by surgery. The discordant subgroup may be a source of false-negative and false-positive results of the assay.
In vitro activity was determined by primary culture of tumor samples obtained at surgery from 63 patients with Stage III ovarian cancer. These patients had completed at least 24 months of follow-up. Proliferative activity was measured after 3-hour culture by 3H-thymidine incorporation and metabolic activity by 3H-uridine incorporation. A large range of individual tumor activity was found; no correlation was present between proliferative and metabolic activity in the same tumor, the distribution of tumors with high and low activity was similar between histologic types, and the activity was not higher in undifferentiated tumors. There was a strong association between in vitro activity of the tumor and patient outcome (both clinical status and survival). On the basis of in vitro activity, a subset of patients was identified within subgroups with known amount of residual tumor; proliferative activity was a better predictor of good outcome in patients with no residual disease, whereas metabolic activity was better in those with more extensive disease. In these patients, a tumor showing high proliferative and/or metabolic activity (greater than 5000 cpm) was associated with poor survival.
D-dimer (DD)--an end product of fibrinolysis--was measured in serum by enzyme immunoassay using a monoclonal antibody to the gamma gamma crosslink in patients with ovarian cancer, before primary surgery and during chemotherapy for 12 months or more. Serial DD levels were found to have a high sensitivity for the detection of tumor in patients with subclinical disease (91%) as well as for predicting progression of disease (100%). As determined by a careful second-look laparotomy in patients with complete clinical remission the DD marker was highly predictive of tumors less than 1 cm. The negative predictive value (82%) was higher than the positive predictive value (69%). However, there were 31% of the patients who showed a false-positive result; a close examination of the clinical data of these 9 patients failed to reveal an explanation for the positive DD levels. Despite the lack of specificity (50% in the present series), the findings support the use of DD in the assessment of patients with ovarian cancer, especially those with subclinical disease.
The in vitro response to cis-diamminodichloroplatinum (cisplatin) in primary culture of tumour samples obtained at surgery was studied in 61 patients with Stage III ovarian cancer who were also treated with cisplatin. The drug-induced inhibitory effect on cell proliferation (measured by 3H-thymidine incorporation) and metabolism (by 3H-uridine incorporation) was assessed over a 3-hour incubation. At greater than or equal to 20% level of inhibition, the true prediction rate of survival by the proliferative assay was 72% among those with 'sensitive' tumours and of mortality was 66% among those with 'resistant' tumours; at greater than or equal to 50% level of inhibition, the prediction rate of survival by the proliferative assay increased to 88% but that of mortality decreased to 58%. The results with the metabolic assay were comparatively lower at all levels. When the amount of residual disease was taken into the determination of mortality rate, significant differences were found between 'sensitive' and 'resistant' tumours as defined by the proliferative assay in patients with no/minimal disease. The pattern of survival differed significantly between 3 subgroups of tumours, as defined by their responses to cisplatin in the proliferative and metabolic assays -- the best survival was obtained in patients whose tumours were 'sensitive' in both assays.
Serial serum CA 125 levels were measured before definitive surgery and during chemotherapy for 12 months or more in 64 patients with ovarian cancer. In the 42 patients who had a complete clinical remission and thus were subjected to a second-look laparotomy, an absence of disease was not predicted by patterns of CA 125 levels. Whilst rising or persistently high levels indicated the presence of tumour in 92% of patients, declining levels to negative predicted the absence of tumour in only 50%. Although the majority of these patients showed microscopic foci or a tumour mass less than 1 cm, 3 patients had a larger amount of disease. In the follow-up of 49 patients, the accuracy of prediction of a good outcome was better than that of a poor outcome on the basis of CA 125 patterns, with rates of 92% and 79%, respectively. Our findings indicate that CA 125 lacks sensitivity in detecting small tumour masses (less than 1 cm dia.) but rising or persistently high levels suggest a strong likelihood of a residual tumour to be found at a second-look laparotomy.
Although the factors involved in the pathophysiology of endometriosis are probably multiple and interrelated, prostaglandins may play an important role in the infertility of women with mild disease. In the present study, prostaglandin F2 alpha (PGF2 alpha) and 17 beta-oestradiol were measured in the peritoneal fluid of a selected group of infertile women who had mild pelvic endometriosis (without anatomical distortion) and compared with those values in normal women who had no pelvic disease and in women with pelvic infection. Although there was a wide scatter of PGF2 alpha values, the mean (1,066 pg/ml) in the endometriosis group was significantly greater than that in the other 2 groups (542 pg/ml, normal and 688 pg/ml, pelvic infection); the increase was found in both phases of the menstrual cycle. The mean concentration of 17 beta oestradiol was markedly higher in the luteal than the follicular phase in all 3 groups; however, no significant differences were found between the groups. Interestingly, the mean value of PGF2 alpha and 17 beta-oestradiol was higher in women with endometriosis who failed to conceive than in those who became pregnant. An estimation of PGF2 alpha in the peritoneal fluid may have prognostic value in the evaluation of infertile patients, especially those with mild endometriosis or in whom the problem is unexplained.
A 3-hour biochemical assay was chosen in the present prospective study to determine the in vitro chemosensitivity of tumours of the ovary, cervix and uterus. The basis of the assay was to determine the ability of a panel of cytotoxic drugs to inhibit the proliferative activity of tumour cells in culture, using 3H thymidine as a precursor of DNA synthesis. We found variability in the in vitro responses of individual tumours to the 4 drugs (cisplatin, adriamycin, melphalan, methotrexate). In ovarian cancer, cisplatin and adriamycin produced the best inhibitory effects; serous cystadenocarcinomas were most frequently inhibited by cisplatin, whilst undifferentiated carcinomas were more affected by adriamycin. Only 14% of tumours were sensitive to all 4 drugs. We found a good correlation between in vitro results and in vivo response in the medium term. For cisplatin, the predictive accuracy was 85% for 'sensitive' tumours and 72% for 'resistant' tumours. These findings should increase our confidence in the test as a new aid to planning of chemotherapeutic strategies.
1,790 postpartum women were asked about their smoking habits and baby feeding practices and about a number of other attitudes and physical attributes. For those variables not concerned with baby feeding, our findings generally support previous research; for example, smokers in comparison to non-smokers tended to have more emotional problems, more reproductive failures and babies with lower birth-weights. For baby feeding, we found that smokers tended to have little prior knowledge of breast feeding, favour bottle feeding, have been fed by bottle by their mothers, and wean earlier than non-smokers or ex-smokers. In fact, non-smokers as a group were similar to breast feeders as a group, and smokers like bottle feeders for over 20 characteristics. These similarities were mostly the result of features of smoking and baby feeding behaviour being found in a common personality type; for example, use of tobacco and choice of bottle feeding are probably attributes of nervous, insecure mothers. But some similarities were the result of the influence of tobacco smoke; for example smokers who do breast feed wean earlier, probably because chemicals in tobacco smoke inhibit milk production.
A survey of postpartum women in Brisbane revealed that many gave up smoking just before or shortly after becoming pregnant, and that many of the remainder reduced their rate of consumption. Husbands who smoked showed no comparable changes in behaviour. Thus apparently many couples were aware of the dangers to the fetus of active smoking by the woman, but not of the dangers of her passive inhalation of smoke. Other significant findings included (i) increasing rates of consumption during successive pregnancies, (ii) high degrees of conformity for most habits (e.g. use of filters), and (iii) stronger addiction and earlier starting ages among heavy smokers than light smokers.
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Samples of ascitic fluid from patients with ovarian cancer were analyzed for autoantibodies to nuclear and cytoplasmic antigens and for immune complexes (ICs) detectable by the Clq deviation and polyethylene glycol (PEG) precipitation (either IgG or IgM class) assays. The predominant autoantibody was antinuclear (ANA); this was detected in 29 of 58 samples (59% showing the homogeneous and 41% the speckled pattern). The antibody was not reactive to saline extractable nuclear antigens. A strong association between this autoantibody and the PEG-precipitated IgM class ICs was shown, suggesting the possible participation of this autoantibody in IgM class ICs formation. The lack of association between C1q-reactive and IgG class ICs and the autoantibodies indicates that the IgG class ICs may be more related to the tumor.
An analysis was made of the ascitic fluid obtained from a patient with serious cyst-adenocarcinoma of the ovary. The fluid contained no reactivity to rheumatoid factor, carcinoembryonic antigen, and autoantigens. The immune complexes in the ascitic fluid, demonstrated by C1q deviation and characterized by gel chromatography, protein A binding studies, and Ouchterlony diffusion, appeared as high molecular weight material. The monomeric IgG dissociated from this material was capable of reassociation into complexes, as shown by radioactive labelling studies. The IgG isolated from the complexes was localized specifically to autologous as well as heterologous malignant ovarian tumor cells but not to normal ovarian tissue by the immunoperoxidase technique.
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Tumor associated immunoglobulins previously isolated from ovarian cancer ascitic fluid have been used in an affinity chromatography step to purify putative tumor associated antigens from a perchloric acid extract of ascitic fluid. Examination of the affinity chromatography purified proteins revealed 4 bands on electrophoresis. Antisera raised to the affinity chromatography products have been examined by Ouchterlony diffusion as well as a solid-phase radioimmunoassay. Two of thirteen ovarian tumor extracts investigated reacted in Ouchterlony diffusion analysis, whereas all thirteen extracts gave positive results in the more sensitive solid-phase radioimmunoassay.
1,790 postpartum women were asked about their breast-feeding attitude, physical and other attitudinal variables. Bivariate analyses were conducted between attitude and each of 38 other variables. Of the causally independent variables, education and occupation were the most strongly related to attitude, and along with doctor's preference were perhaps the most important influences on a mother's baby-feeding attitude. No physical or health measure was strongly related to attitude towards breast-feeding, although there were consistent associations between favourable attitudes and optimal categories of the physical and health variables. A hypothesized model of the influences on breast-feeding attitude and behaviour is presented.