Symptoms and diagnosis of borderline, early and advanced epithelial ovarian cancer

Objective. To document symptoms associated with borderline, early and advanced ovarian cancer and identify personal characteristics associated with early versus late diagnosis. Methods. Information concerning symptoms and diagnosis history was available from 811 women with ovarian cancer who took part in an Australian case–control study in the early 1990s. Women were classified into three groups for comparison based on their diagnosis: borderline, early (stage I–II) and advanced (stage III–IV) invasive cancer. Results. Sixteen percent of women with borderline tumors, 7% with early cancer and 4% with advanced cancer experienced no symptoms before diagnosis (P < 0.0001). Among women with symptoms, abdominal pain (44%) or swelling (39%) were most frequently reported; an abdominal mass (12%) and gynecological symptoms (12%) were less common. Compared to advanced stage cancer, women with early stage cancer were more likely to report an abdominal mass or urinary symptoms but less likely to report gastrointestinal problems or general malaise. General malaise and ‘other’ symptoms were least common in borderline disease. Older women, and those with higher parity or a family history of breast or ovarian cancer, were more likely to be diagnosed at an advanced stage of disease. Conclusions. Women who experience persistent or recurrent abdominal symptoms, particularly swelling and/or pain should be encouraged to seek medical attention and physicians should be alert to the possibility of ovarian cancer even in the absence of an abdominal mass. Further information about the prevalence of these symptoms in the general population is essential to assist physicians in patient management.

Modeling the relationships between adult attachment patterns and borderline personality disorder: The role of impulsivity and aggressiveness

To obtain a better understanding of the associations among Borderline Personality Disorder (BPD), adult attachment patterns, impulsivity, and aggressiveness, we tested four competing models of these relationships: a) BPD is associated with the personality traits of impulsivity and aggressiveness, but adult attachment patterns predict neither BPD nor impulsive/aggressive features; b) adult attachment patterns are significant predictors of BPD but not of impulsive/aggressive traits, although these traits correlate with BPD; c) adult attachment patterns are significant predictors of impulsive and aggressive traits, which in turn predict BPD; and d) adult attachment patterns significantly predict both BPD and impulsive/aggressive traits. We assessed 466 consecutively admitted outpatients using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (V. 2.0), the Attachment Style Questionnaire, the Barratt Impulsiveness Scale-11, and the Aggression Questionnaire. Maximum likelihood structural equation modeling of the covariance matrix showed that model (c) was the best fitting model (chi(2) (21) = 31.67, p >.05, RMSEA = .023, test of close fit p >.85). This result indicates that adult attachment patterns act indirectly as risk factors for BPD because of their relationships with aggressive/impulsive personality traits.

An investigation of organic factors in the neuropsychological functioning of patients with borderline personality disorder

The hypothesis to be tested in this study was that the cognitive deficits that have been documented in patients with Borderline Personality Disorder (BPD) are largely the consequence of organic insult, either developmental or acquired. Using a cross-sectional design, 80 subjects (males and females) who met the criteria for BPD participated in the study. They completed a battery of neuropsychological tests and a comprehensive interview assessing organic status as well as measures of the potentially confounding factors of current levels of depression and anxiety. It was expected that BPD-patients with a probable history of organic insult would perform significantly worse than would BPD patients without such a history. Analyses of the results provided partial support for the hypothesis. Subjects with both BPD and a history of organic insult were significantly more impaired on several measures including measures of attention than were BPD only subjects. The results suggested that the impaired cognitive performance of persons diagnosed with BPD may, in part, be attributed to organic factors.

Variable temperature and pressure study of the aquation reactions of cobalt(III) and chromium(III) penta- and tetra-amines

Preparation of a series of specific penta- and tetra-amine derivatives of Co-III and Cr-III with a neutral leaving ligand has been carried out in order to accomplish a fine tuning of the associativeness/dissociativeness of their substitution reactions. Spontaneous aquation reactions of the neutral ligands have been studied at variable temperature and pressure. Although rate constants and thermal activation parameters show an important degree of scatter, the values determined for the activation volumes of the substitution process illustrate the mechanistic fine tuning that may be achieved for these reactions. In all cases, in the absence of important steric constraints in the molecule, electronic inductive effects seem to be the most important factor accounting for the dissociative shifts observed both for pentaamine (i.e.Delta V double dagger=+4.0 or +14.0 cm(3) mol(-1) and +5.2 or +16.5 cm(3) mol(-1) for the aquation of cis- or trans-[Co(MeNH2)(NH3)(4)(DMF)](3+) and cis- or trans-[CoL15(DMF)](3+) respectively, where L-15 represents a pentaamine macrocyclic ligand), and tetraamine systems (i.e.Delta V double dagger=+4.1 or +8.4 cm(3) mol(-1) and -10.8 or -7.4 cm(3) mol(-1) for the aquation of cis-[Co(NH3)(4)Cl(DMAC)](2+) (DMAC=dimethylacetamide) or cis-[Co(en)(2)Cl(DMAC)](2+) and cis-[Cr(NH3)(4)Cl(DMF)](2+) or cis -[Cr(en)(2)Cl(DMF)](2+)). From the results, clear evidence is obtained which indicates that, only when the situation is borderline I-a/I-d, or the steric demands are increased dramatically, dissociative shifts are observed; in all other cases electronic inductive effects seem to be dominant for such a tuning of the substitution process.

Beyond ovulation: Oral contraceptives and epithelial ovarian cancer

In a case-control study in three Australian states that included 794 women with epithelial ovarian cancer and 853 community controls for whom we had adequate contraceptive and reproductive histories, Re examined the effects of oral contraceptive use after controlling for estimated number of ovulatory cycles. Other covariates included in the multiple logistic regression analysis were parity, smoking, and history of pelvic surgery. The protective effect of duration of oral contraceptive use appeared to be multiplicative, with a 7% decrease in relative risk per year [95% confidence interval (CI) = 4-9%], persisting beyond 15 years of exposure. Use for up to 1 year may have a greater effect than predicted (odds ratio = 0.57; 95% CI = 0.40-0.82), whereas use before the first pregnancy may be additionally beneficial (odds ratio = 0.95; 95% CI = 0.87-1.03, adjusted for overall duration of use). Better control for ovulatory life might attenuate these estimates somewhat. There was little evidence of waning protection with time since last exposure or of extra benefit with early commencement of oral contraceptive use. We found no convincing evidence of effect modification in any factor examined or differences in effect among the three main histologic cancer types or between borderline and malignant tumors. Oral contraceptives may act by both suppressing ovulation and altering the tumor-promoting milieu.

Hormonal factors and risk of aneurysmal subarachnoid hemorrhage - An international population-based, case-control study

Background and Purpose-Subarachnoid hemorrhage (SAH) is more common in women than in men, but the role of hormonal factors in its etiology remains uncertain. The aim of this study was to examine the relationship between hormonal factors and risk of SAH in women. Methods-This was a prospective, multicenter, population-based, case-control study performed in 4 major urban centers in Australia and New Zealand. Two hundred sixty-eight female cases of first-ever aneurysmal SAH occurred during 1995-1998. Controls were 286 frequency-matched women from the general population of each center. Outcome measures included risk of SAH associated with use of oral contraceptive pills (OCPs), hormone replacement therapy (HRT), and various endogenous hormonal factors including menstrual patterns, parity, age at birth of first child, and breast-feeding practices. Results-Cases and controls did not differ with regard to menstrual and reproductive history except in age at bir th of first child, where older age was associated with reduced risk of SAH (odds ratio [OR], 0.63; 95% CI, 0.43, 0.91). Relative to never use of HRT, the adjusted OR for over use of HRT was 0.64 (95% CI, 0.41, 0.98), which did not alter significantly after further adjustment for possible confounding factors. Borderline evidence of an inverse association was detected for past use of HRT (adjusted OR, 0.59; 95% CI, 0.30, 1.13) and current use of HRT (adjusted OR, 0.67; 95% CI, 0.40, 1.13), but there was no evidence of an association for use of OCPs (adjusted OR, 0.97; 95% CI, 0.58, 1.60). Conclusions-The risks of SAH are lower in women whose first pregnancy is at an older age and women who have ever used HRT but not OCPs. The findings suggest an independent etiologic role for hormonal factors in the pathogenesis of aneurysmal SAH and provide support for a protective role fur HRT on risk of SAH in postmenopausal women.

EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer

EDD (E3 isolated by differential display), located at chromosome 8q22.3, is the human orthologue of the Drosophila melanogaster tumour suppressor gene 'hyperplastic discs' and encodes a HECT domain E3 ubiquitin protein-ligase. To investigate the possible involvement of EDD in human cancer, several cancers from diverse tissue sites were analysed for allelic gain or loss (allelic imbalance, AI) at the EDD locus using an EDD-specific microsatellite, CEDD, and other polymorphic microsatellites mapped in the vicinity of the 8q22.3 locus. Of 143 cancers studied, 38 had AI at CEDD (42% of 90 informative cases). In 14 of these cases, discrete regions of imbalance encompassing 8q22.3 were present, while the remainder had more extensive 8q aberrations. AI of CEDD was most frequent in ovarian cancer (22/47 informative cases, 47%), particularly in the serous subtype (16/22, 73%), but was rare in benign and borderline ovarian tumours. AI was also common in breast cancer (31%), hepatocellular carcinoma (46%), squamous cell carcinoma of the tongue (50%) and metastatic melanoma (18%). AI is likely to represent amplification of the EDD gene locus rather than loss of heterozygosity, as quantitative RT-PCR and immunohistochemistry showed that EDD mRNA and protein are frequently overexpressed in breast and ovarian cancers, while among breast cancer cell lines EDD overexpression and increased gene copy number were correlated. These results demonstrate that AI at the EDD locus is common in a diversity of carcinomas and that the EDD gene is frequently overexpressed in breast and ovarian cancer, implying a potential role in cancer progression.

Cigarette smoking and risk of epithelial ovarian cancer (Australia)

Objectives: We studied the association between cigarette smoking and ovarian cancer in a population-based case-control study. Methods: A total of 794 women with histologically confirmed epithelial ovarian cancer who were aged 18-79 years and resident in one of three Australian states were interviewed, together with 855 controls aged 18-79 years selected at random from the electoral roll from the same states. Information was obtained about cigarette smoking and other factors including age, parity, oral contraceptive use, and reproductive factors. We estimated the relative risk of ovarian cancer associated with cigarette smoking, accounting for histologic type, using multivariable logistic regression to adjust for confounding factors. Results: Women who had ever smoked cigarettes were more likely to develop ovarian cancer than women who had never smoked (adjusted odds ratio (OR) = 1.5; 95% confidence interval (CI) = 1.2-1.9). Risk was greater for ovarian cancers of borderline malignancy (OR = 2.4; 95% CI = 1.4-4.1) than for invasive tumors (OR = 1.7; 95% CI = 1.2-2.4) and the histologic subtype most strongly associated overall was the mucinous subtype among both current smokers (OR = 3.2; 95% CI = 1.8-5.7) and past smokers (OR = 2.3; 95% CI = 1.3-3.9). Conclusions: These data extend recent findings and suggest that cigarette smoking is a risk factor for ovarian cancer, especially mucinous and borderline mucinous types. From a public health viewpoint, this is one of the few reports of a potentially avoidable risk factor for ovarian cancer.

Phyllodes tumors of the breast: Correlation of nucleolar organizer regions with histopathological malignancy grading, flow cytometric DNA analysis and clinical outcome

To examine whether nucleolar organizer regions detected by argyrophilia (Ag-NOR counts) can be used as a prognostic indicator in phyllodes tumors of the breast, and to compare its usefulness with that of DNA flow cytometric analysis, 28 cases of breast phyllodes tumors (including 15 benign, two borderline and 11 malignant tumors) were subjected to Ag-NOR staining and counting as well as DNA flow cytometric analysis. S-phase fraction and DNA ploidy analysis showed useful trends for improving outcome predictions in malignant phyllodes tumors. However, high Ag-NOR counts were significant in predicting survival status (P = 0.013) and reached near statistical significance in predicting survival times (P = 0.07). In predicting survival status, results for Ag-NOR counts were significantly better than those for ploidy analysis (P = 0.02) and S-phase fraction (P < 0.01). Only S-phase fraction was significantly predictive of survival times (P = 0.025). It is concluded that Ag-NOR counts and DNA flow cytometric analysis, easily performed using paraffin sections, give information that can improve predictions made by histopathological classification. Ag-NOR counts are significant in predicting survival in the presence of histopathological features of malignancy.

Genetic and environmental risk factors and their interactions for Parkinson's disease in a Chinese population

The interaction between genetic and environmental factors for PD was examined in a Chinese population. It was found that although the intron 2 MAOB (GT)(n) repeat polymorphism was not associated with PID in the population, a relationship might have been masked by the protective effect of tea drinking. In individuals who did not drink tea (<1 cup/day), the possession of short length less than or equal to 178 bp (GT), alleles conferred a borderline significant increased risk for PD (adjusted OR = 1.47; C.l. = 1.03-2. 1). As the extent of tea consumption increased, the association between the less than or equal to178 bp allele and PD disappeared. This result suggests that the MAOB gene may be associated with PD in Chinese if the putative protective effect of tea drinking is taken into account. The significance of this finding is unclear as the study may be limited because of its marginal significance and limited numbers. However, it does demonstrate the importance of considering putative positive and negative environmental risk factors in any examination of genetic risk factors for PD. (C) 2003 Elsevier Science Ltd. All rights reserved.

Dietary influences on survival after ovarian cancer

We evaluated the effects of various food groups and micronutrients in the diet on survival among women who originally participated in a population-based case-control study of ovarian cancer conducted across 3 Australian states between 1990 and 1993. This analysis included 609 women with invasive epithelial ovarian cancer, primarily because there was negligible mortality in women with borderline tumors. The women's usual diet was assessed using a validated food frequency questionnaire. Deaths in the cohort were identified using state-based cancer registries and the Australian National Death Index (NDI). Crude 5-year survival probabilities were estimated using the Kaplan-Meier technique, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression models. After adjusting for important confounding factors, a survival advantage was observed for those who reported higher intake of vegetables in general (HR = 0.75, 95% CI = 0.57-0.99, p-value trend 0.01 for the highest third, compared to the lowest third), and cruciferous vegetables in particular (HR = 0.75, 95% CI = 0.57-0.98, p-value trend 0.03), and among women in the upper third of intake of vitamin E (HR = 0.76, 95% CI = 0.58-1.01, p-value trend 0.04). Inverse associations were also seen with protein (p-value trend 0.09), red meat (p-value trend 0.06) and white meat (p-value trend 0.07), and modest positive trends (maximum 30% excess) with lactose (p-value trend 0.04), calcium and dairy products. Although much remains to be learned about the influence of nutritional factors after a diagnosis of ovarian cancer, our study suggests the possibility that a diet high in vegetable intake may help improve survival. (C) 2003 Wiley-Liss, Inc.

Improving family functioning and child outcome in methadone maintained families: the Parents Under Pressure programme

Twelve families responded to posters displayed in a methadone clinic for inclusion in a pilot study assessing the viability and potential utility of an intensive, multi-component family-focused intervention, the Parents Under Pressure programme. The programme was designed to improve child behaviour, decrease parental stress and improve family functioning in methadone-maintained families by targeting affect regulation, mood, views of self as a parent, drug use and parenting skills. Nine of the families completed the programme delivered in their homes; eight were recontacted at 3 months. Each family reported significant improvements in three domains: parental functioning, parent - child relationship and parental substance use and risk behaviour. In addition to the changes in family functioning, the majority of families reported a decrease in concurrent alcohol use, HIV risk-taking behaviour and maintenance dose of methadone. The families reported high levels of satisfaction with the programme. It is recommended that future studies include independent measures (e.g. behavioural observations) of child outcome and parental functioning. The results were optimistic and provided the impetus to evaluate the treatment programme using a randomized controlled trial.

On the dimensionality of the Attachment Style Questionnaire in Italian clinical and nonclinical participants

This study examined the utility of the Attachment Style Questionnaire (ASQ) in an Italian sample of 487 consecutively admitted psychiatric participants and an independent sample of 605 nonclinical participants. Minimum average partial analysis of data from the psychiatric sample supported the hypothesized five-factor structure of the items; furthermore, multiple-group component analysis showed that this five-factor structure was not an artifact of differences in item distributions. The five-factor structure of the ASQ was largely replicated in the nonclinical sample. Furthermore, in both psychiatric and nonclinical samples, a two-factor higher order structure of the ASQ scales was observed. The higher order factors of Avoidance and Anxious Attachment showed meaningful relations with scales assessing parental bonding, but were not redundant with these scales. Multivariate normal mixture analysis supported the hypothesis that adult attachment patterns, as measured by the ASQ, are best considered as dimensional constructs.

Personality disorders and adult attachment dimensions in a mixed psychiatric sample: A multivariate study

The associations between personality disorders and adult attachment dimensions were assessed in a sample of 487 consecutively admitted psychiatric subjects. Canonical correlation analysis showed that two sets of moderately correlated canonical variates explained the correlations between personality disorders and adult attachment patterns. The first and second attachment variates closely resembled the avoidance and anxiety attachment dimensions, respectively. The first personality disorder variate was mainly characterized by avoidant, depressive, paranoid, and schizotypal personality disorders, whereas dependent, histrionic, and borderline personality disorders loaded on the second canonical variate. However, these linear combinations of personality disorders were different from those obtained from principal component analysis. The results extend previous studies linking personality disorders and attachment patterns and suggest the importance of focusing on specific constellations of symptoms associated with dimensions of insecurity.