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Biomedical subjects

M C Cummings

Publications and source records attributed to M C Cummings.

At least 19 recordsLinked to original sources
PubMed1999

Improving cervical cytology screening in a remote, high risk population.

OBJECTIVE: To evaluate the use of the ThinPrep method to reduce rates of unsatisfactory Papanicolaou (Pap) smears in women in remote communities. DESIGN: Prospectively collected samples were split and screened conventionally and by ThinPrep at the Queensland Cytology Service. PATIENTS: Three hundred women having cervical smears taken by a Mobile Women's Health Service nurse or at the antenatal and sexual health clinics of a remote north Queensland community. MAIN OUTCOME MEASURE: Number of Pap smears reported as unsatisfactory for evaluation and requiring a repeat smear request. RESULTS: 17.3% of conventionally prepared smears were technically unsatisfactory, compared with 6.3% prepared with ThinPrep. The overall rate of unsatisfactory smears was only 4.3% when both ThinPrep and conventional smears were assessed for a combined report. CONCLUSION: A significant reduction in the proportion of unsatisfactory Pap smears is possible with the ThinPrep method. Targeted use of ThinPrep in communities with high rates of unsatisfactory smears may prove cost-effective.

Adolescent↗
PubMed1998

Relationship between number of ovulatory cycles and accumulation of mutant p53 in epithelial ovarian cancer.

BACKGROUND: It has been suggested that increased numbers of ovulations might increase the risk of p53 gene (also known as TP53) mutation in the ovarian epithelium, thereby leading to the development of cancer. The data supporting this hypothesis have come from an observation that accumulation of p53 protein in epithelial ovarian cancer was strongly associated with increasing numbers of ovulatory cycles. We have further investigated the association between ovulatory history and p53 gene mutation by use of data from a large case-control study of ovarian cancer in Australia. METHODS: Tissue blocks were available for immunohistochemical analysis of p53 protein from 234 case subjects, aged 18-79 years, who had invasive epithelial ovarian cancer. Epidemiologic data were also available for these women and for 855 control subjects. Case-case comparisons were made by use of prevalence ratios and 95% confidence intervals (CIs), and case-control comparisons were made by use of odds ratios (ORs) and 95% CIs. All statistical tests were two-sided. RESULTS: There was no association between p53 accumulation and years of ovulation. Women with p53-positive cancers had undergone an average of 29.3 years of ovulation compared with 29.0 years of ovulation for women with p53-negative cancers (P=.8). Although the overall risk of ovarian cancer development was significantly increased in women who had undergone more years of ovulation (OR=2.17; 95% CI =1.54-3.05-for > or =35 years versus <23 years of ovulation), there was no difference in the risk associated with p53-positive and p53-negative cancers. CONCLUSIONS: These results confirm the association between increased ovulation and ovarian cancer risk but do not support the hypothesis that this association is due to an increased risk of p53 mutation with a greater number of ovulatory cycles.

Adult↗
PubMed1997

Reduced expression of retinoblastoma gene product (pRB) and high expression of p53 are associated with poor prognosis in ovarian cancer.

Paraffin sections (n = 168, 27 benign, 16 low malignant potential [LMP] and 125 malignant tumours) from epithelial ovarian tumours were evaluated immunohistochemically for expression of retinoblastoma gene product (pRB) and p53 protein, and the relationship among pRB, p53 and cyclin-dependent kinase inhibitor 2 (CDKN2) gene product p16INK4A (p16) was analysed, following our previous study of p16. Forty-one percent of the benign, 50% of the LMP and most (71%) of the malignant tumours showed high pRB expression. High expression of pRB (>50% pRB-positive cells) significantly correlated with non-mucinous histological subtypes. Reduced pRB expression, substage and residual disease were significant predictors for poor prognosis in stage I patients. All the benign and most of the LMP (81%) tumours were in either the p53-negative or low p53-positive category, but nearly half of the malignant tumours had high p53 expression. High p53 accumulation was found in non-mucinous, high grade and late stage tumours. For well-differentiated carcinomas, high p53 expression was a predictor of poor prognosis. However, even though high p53 expression was not associated with histological subtype, stage or the presence of residual disease, high p53 expression was not an independent predictor when all clinical parameters were combined. For all ovarian cancers, a close correlation was found between high p53 and high p16 expression. The relationship between the expression of pRB and p16 depended on tumour stage. In stage I tumours, high pRB was associated with low p16 reactivity. On the other hand, most advanced tumours showed both high pRB and high p16 reactivity.

Carrier Proteins↗
PubMed1997

Increased expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product P16INK4A in ovarian cancer is associated with progression and unfavourable prognosis.

Paraffin sections from 190 epithelial ovarian tumours, including 159 malignant and 31 benign epithelial tumours, were analysed immunohistochemically for expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product p16INK4A (p16). Most benign tumours showed no p16 expression in the tumour cells, whereas only 11% of malignant cancers were p16 negative. A high proportion of p16-positive tumour cells was associated with advanced stage and grade, and with poor prognosis in cancer patients. For FIGO stage I tumours, a high proportion of p16-positive tumour cells was associated with poorer survival, suggesting that accumulation of p16 is an early event of ovarian tumorigenesis. In contrast to tumour cells, high expression of p16 in the surrounding stromal cells was not associated with the stage and grade, but was associated with longer survival. When all parameters were combined in a multivariate analysis, high p16 expression in stromal cells was not an independent predictor for survival, indicating that low p16 expression in stromal cells is associated with other markers of tumour progression. High expression of p16 in the stromal cells of tumours from long-term survivors suggests that tumour growth is limited to some extent by factors associated with p16 expression in the matrix.

Biomarkers, Tumor↗
PubMed1997

Expression of MUC1 and MUC2 mucins in epithelial ovarian tumours.

This is the first study to describe the association between expression of MUC1 and MUC2 mucins and prognosis in ovarian cancer. Paraffin sections of epithelial ovarian tumours (n = 182: 29 benign, 21 low malignant potential, and 132 invasive tumours) were analysed immunohistochemically for expression of MUC1 and MUC2 mucin core proteins. Most benign, low malignant potential, and invasive tumours showed high MUC1 expression in the cytoplasm. Low cytoplasmic expression of MUC1 was a predictor for good prognosis, particularly within stage III tumours. A minority of benign epithelial tumours, but most low malignant potential and invasive non-mucinous tumours, showed high MUC1 expression on the cell membrane. High apical MUC1 reactivity was associated with non-mucinous tumours. Low expression of MUC1 in the apical membrane was associated with early stage and good outcome for invasive tumours. Most benign and low malignant potential tumours, but only a minority of invasive tumours, showed MUC2 expression. MUC2 was found in non-mucinous as well as in mucinous tumours. The presence of MUC2 was inversely associated with high tumour grade but was not associated with altered survival. These results support experimental evidence that MUC1 influences the metastatic ability of ovarian cancer.

Adolescent↗
PubMed1997

Apoptosis.

Explore the source record for details and available documents.

Animals↗
PubMed1996

Increased p53 mRNA expression in liver and kidney apoptosis.

The role of p53 in apoptosis is unclear; it is essential for the apoptotic response to certain stimuli, such as ionising radiation, but it is not required for others, such as castration-induced prostatic atrophy. Various tumour cell lines that are without functioning p53 are enabled to undergo apoptosis by transfecting wild type 53. The regulation of p53 mRNA is determined here, in two in vivo models of apoptosis. The first is partial liver ischaemic atrophy due to distal portal vein ligation, and the second is unilateral hydronephrosis from ureteric ligation. Mild ischaemia and elevated pressure, respectively, are thought to both cause mild cellular damage, induction of p53 and cell death by apoptosis. In both models of apoptosis, upregulation of p53 is shown.

Animals↗
PubMed1996

Occult axillary node metastases in breast cancer: their detection and prognostic significance.

Although the presence of axillary node metastases in breast cancer is a key prognostic indicator and may influence treatment decisions, a significant proportion of patients diagnosed as axillary node negative (ANN) using standard histopathological techniques may have occult nodal metastases (OMs). A combination of limited step-sectioning (4 x 100 microns intervals) and immunohistochemical staining (with cytokeratin (MNF.116) and MUC1 (BC2) antibodies) was used to detect OM in a retrospective series of 208 ANN patients. OMs were found in 53 patients (25%), and both step-sectioning and immunohistochemical detection significantly improved detection (P < 0.05). Detection using BC2 (25%) was superior to MNF.116 (18%) and haematoxylin and eosin (H&E) (8%). OMs were found in 51 patients using only the first and deepest sectioning levels and BC2 staining. OMs were more frequently found in lobular (38%) than ductal carcinoma (25%), and more frequently in women less than 50 years (41%) than in older women (19%). Univariate overall and disease-free survival analyses showed that the presence, size and number of OM had prognostic significance as did tumour size (disease-free only) and histological and nuclear grade (P > 0.05). Cox multivariate proportional hazard regression analyses showed that the presence and increasing size of OMs were significantly associated with poorer disease-free survival, independently of other prognostic factors (P < 0.05). However there was not a significant independent association of the presence of occult metastases with overall survival (P = 0.11). These findings have important implications with regard to selection of ANN patients for adjuvant therapy.

Adult↗
PubMed1995

Interaction between murine germline mutations in p53 and APC predisposes to pancreatic neoplasia but not to increased intestinal malignancy.

Murine strains which bear constitutive inactivating mutations of either the APC or the p53 tumor suppressor genes are characterised by spontaneous tumors. APC mutated (Min) mice develop large and small bowel adenomas, a small proportion of which, in time, become malignant. p53 deficient mice develop predominantly lymphoma and sarcoma. By interbreeding these strains we have shown that there is co-operativity between these mutations, leading to a shift in phenotype. Most notably, this was characterised by a range of abnormalities of the exocrine pancreas in 83% of animals heterozygous for the APC mutation and constitutively null for functional p53. Dysplasia and preneoplastic foci were seen in 61% of these animals and pancreatic acinar cell adenocarcinoma in 22%. Analysis of these tumors showed them to have lost the remaining wild-type copy of APC. Similar loss of APC was not associated with the development of other extra-intestinal tumors. Surprisingly, given the proposed role for loss of function mutations of the p53 gene in the development of human colorectal cancer, we have found no evidence for either an increase in the rate of adenoma formation in APC +/-, p53 -/- animals, or an increased rate of progression to malignancy compared with APC +/- p53 +/+ mice. These findings highlight striking tissue-specific differences in the tumor suppressor effects of p53.

Adenocarcinoma↗
PubMed1995

Bacterial vaginosis in lesbians: a sexually transmitted disease.

Sexual transmission of bacterial vaginosis (BV), a common syndrome in sexually active women, has not been previously established. Because no male counterpart for BV has been found, a population of lesbians is an ideal one in which to test the hypothesis that BV is sexually transmitted. We studied 103 homosexual women (lesbians) who sought gynecologic care at a community clinic and in a private gynecology practice in New York City. Participants were asked to refer their sexual partners for evaluation. In this cross-sectional prevalence study, all participants were evaluated for the presence of BV, and pairs of monogamous sexual partners were analyzed for concordance of their vaginal secretions. Twenty-nine (28.7%) of the 101 participants from whom satisfactory vaginal wash samples were available had BV. There were 21 pairs of monogamous partners. Of 11 index women who had BV, eight (72.7%) had partners who also had BV. Of 10 index women who did not have BV, only one (10%) had a partner with BV. The likelihood of a partner's having BV was 19.7 times greater if the index case had BV (P < .008; 95% CI, 2.1-588.0). We conclude that with respect to BV, lesbians in monogamous relationships usually have concordant vaginal secretions. This concordance probably reflects the sexual transmission of BV between lesbians.

Female↗
PubMed1993

Identification of mycoplasmas in urine from persons infected with human immunodeficiency virus.

Voided urine samples from persons with and without human immunodeficiency virus (HIV) infection were examined for mycoplasmas. Mycoplasma hominis organisms were identified in cultures of urine from 32 (18%) of 180 HIV-positive individuals and from 8 (21%) of 38 HIV-negative individuals. In contrast, glucose-utilizing mycoplasmas were identified in the urine of 30 (17%) of the HIV-positive individuals and in none of those who were HIV-negative. Assays of growth inhibition around disks containing specific antisera identified 14 of the 30 glucose-utilizing mycoplasmas as Mycoplasma fermentans. Four isolates were presumptively identified as Mycoplasma pirum. Growth on solid media was insufficient to permit the identification of the species of the other 12 isolates by growth inhibition.

Adult↗
PubMed1993

PCNA immunostaining in breast cancer.

Expression of proliferating cell nuclear antigen (PCNA) has been shown to be of prognostic value in patients with certain types of cancer. The aim of this study was to determine if the abundance of PCNA is inversely correlated with survival of patients with breast cancer. Paraffin blocks were available from 68 patients, all of whom had been followed clinically for at least 5 years. Sections from 20 patients showed no reactivity to PCNA and were excluded from the study because it was not possible to distinguish between true negatives and false negatives (those due to poor fixation of the original specimens). The PCNA index (the number of stained cancer cells as a percentage of the total number of cancer cells present) was calculated for the remaining 48 patients. Results were analysed by Wilcoxon's rank sum test (two tailed) and Pearson's correlation coefficient. There was no statistical difference between the PCNA indices of those patients dead from their disease within 5 years of diagnosis compared with those alive and without signs of breast cancer at 5 years. There was also no correlation between PCNA index and size of the cancer, involvement of axillary lymph nodes, time to recurrence or time to death. There was, however, a significant correlation between PCNA index and histological grade (P = 0.029). It appears that PCNA staining of stored paraffin sections is of little prognostic value in patients with breast cancer.

Antibodies, Monoclonal↗
PubMed1990

Increase in resistance of Mycoplasma hominis to tetracyclines.

Isolates of Mycoplasma hominis collected from patients in Boston and New York between 1976 and 1989 were studied. Minimal metabolism-inhibiting concentrations (MMCs) were determined by use of a terminal color change-broth dilution method, as well as by an agar inoculum-broth dilution method. Both methods gave comparable results. Tetracycline MMCs for 3 (7.0%) of 43 isolates of M. hominis collected from 1976 to 1979 were 8 micrograms/ml or more, but they were 8 micrograms/ml or more for 11 (20.3%) of 54 isolates collected from 1980 to 1983 (P = 0.083) and 16 (26.6%) of 60 isolates collected from 1984 to 1989 (P = 0.019). Similarly, doxycycline MMCs for 0 of 43 isolates of M. hominis collected from 1976 to 1979 were 8 micrograms/ml or more, but they were 8 micrograms/ml or more for 8 (14.8%) of 54 strains isolated from 1980 to 1983 (P = 0.0082) and 10 (16.6%) of 60 strains isolated from 1984 to 1989 (P = 0.0047). The susceptibility of M. hominis to clindamycin did not change. We conclude that isolates of M. hominis in the northeastern United States have become more resistant to tetracycline and doxycycline over the past decade.

Clindamycin↗
PubMedDate not supplied

Evaluation of ofloxacin in the treatment of uncomplicated gonorrhea.

In an open study, a single oral dose of 400 mg of ofloxacin was administered to 40 men and 20 women who required treatment for uncomplicated gonococcal infection. Thirty-six men and 13 women were evaluable. Ofloxacin eradicated 49 of 49 urethral or endocervical gonococcal infections and 1 of 1 pharyngeal infection. There were 55 pretreatment isolates of Neisseria gonorrhoeae available for antimicrobial susceptibility testing. Twenty-four (43.6%) produced penicillinase. Eighteen (32.7%) isolates that did not produce penicillinase had penicillin MICs greater than or equal to 1.0 micrograms/mL. Twelve (21.8%) isolates had tetracycline MICs greater than or equal to 16 micrograms/mL. The geometric mean minimal inhibitory concentrations (range) for 55 pretreatment N. gonorrhoeae isolates were: ofloxacin, 0.014 (.0078-.03) micrograms/mL; penicillin, 6.30 (.125-128) micrograms/mL; and tetracycline 1.61 (.03-128) micrograms/mL. There were few side effects. Ofloxacin appears to be an effective and safe oral therapy for the treatment of infections caused by N. gonorrhoeae including infections due to penicillin- and tetracycline-resistant strains.

Adult↗