Menopause status and climacteric symptoms in a birth cohort of mid-life New Zealand women.

BACKGROUND: There is little current research on the transition to natural menopause among contemporary groups of mid-life women at age 40 years. OBJECTIVE: This study reports on female members of the Christchurch Health and Development Study cohort. This research aimed to: document the menopause status, reproductive outcomes and climacteric symptoms of the women at age 40 years; examine the associations between menopause status and concurrent measures of psychosocial and economic well-being; and document the associations between menopause status and potential predictors of menopause reflecting childhood, family and individual factors prior to age 40 years. METHODS: The Christchurch Health and Development Study is a longitudinal, representative, prospective cohort of 1265 babies (630 females) born in New Zealand in 1977. At age 40 years, 470 women (who had not experienced surgical menopause) were interviewed on their menopause status, climacteric symptoms and associated factors. RESULTS: The majority of women were premenopausal, around 20% were perimenopausal and 2% were postmenopausal. Statistically significant associations were found reflecting higher rates of diagnosed reproductive disorder, climacteric symptoms, low occupational status, non-heterosexual sexuality and exposure to childhood sexual abuse amongst both perimenopausal and postmenopausal women at age 40 years. CONCLUSION: These data will inform directions for future data collection and analyses.

Sexual orientation and mental health over the life course in a birth cohort.

BACKGROUND: Sexual minority individuals consistently report higher rates of mental disorder than heterosexuals. However, much of the research has methodological limitations related to the classification of sexuality, the use of cross-sectional data and problematic sampling procedures such as using convenience samples. METHODS: We used longitudinal data from a birth cohort enrolled in the Christchurch Health and Development Study (n = 1040). Latent class analysis was used to classify participants sexuality based on self-report data of sexual behaviour, attraction, identity and fantasy, gathered over five assessments between the ages of 18 and 35 years. Mental health and substance use outcome data were gathered at four assessments between the ages of 21 and 35 years. Potential covariate variables were collected during childhood. RESULTS: The latent class analysis identified four groups interpreted as: 'heterosexual' 82%, 'mostly heterosexual' 12.6%, 'bisexual' 3.5% and 'gay/lesbian' 1.9%. In the sexual minority groups, women outnumbered men by at least 2:1. Pooled rates for mental health disorders of depression, anxiety disorders, suicidal ideation, cannabis abuse and total disorders, after adjustment for childhood covariate variables, were significantly higher in the sexual minority groups (p < 0.01). The strength of association between sexuality group and mental health outcomes did not differ according to sex. Fluidity in sexuality reports appeared unrelated to risk of mental health outcomes. CONCLUSIONS: Over the life course, membership of a sexual minority group is clearly associated with mental health problems of depression, anxiety and suicidal ideation regardless of the age when same-sex attraction, behaviour, identity or fantasy is expressed.

Ten month outcome of cognitive behavioural therapy v. interpersonal psychotherapy in patients with major depression: a randomised trial of acute and maintenance psychotherapy.

BACKGROUND: Cognitive behaviour therapy (CBT) and interpersonal psychotherapy (IPT) are the most studied psychotherapies for treatment of depression, but they are rarely directly compared particularly over the longer term. This study compares the outcomes of patients treated with CBT and IPT over 10 months and tests whether there are differential or general predictors of outcome. METHODS: A single centre randomised controlled trial (RCT) of depressed outpatients treated with weekly CBT or IPT sessions for 16 weeks and then 24 weeks of maintenance CBT or IPT. The principle outcome was depression severity measured using the MADRS. Pre-specified predictors of response were in four domains: demographic depression, characteristics, comorbidity and personality. Data were analysed over 16 weeks and 40 weeks using general linear mixed effects regression models. RESULTS: CBT was significantly more effective than IPT in reducing depressive symptoms over the 10 month study largely because it appeared to work more quickly. There were no differential predictors of response to CBT v. IPT at 16 weeks or 40 weeks. Personality variables were most strongly associated with overall outcome at both 16 weeks and 40 weeks. The number of personality disorder symptoms and lower self-directness and reward dependence scores were associated with poorer outcome for both CBT and IPT at 40 weeks. CONCLUSIONS: CBT and IPT are effective treatments for major depression over the longer term. CBT may work more quickly. Personality variables are the most relevant predictors of outcome.

Bullying victimization in adolescence and psychotic symptomatology in adulthood: evidence from a 35-year study.

BACKGROUND: There has been considerable recent interest in possible causal linkages between exposure to bullying victimization and later psychotic symptomatology. Prior research in this area has had several limitations which make it difficult to ascertain causality, and to determine the extent to which these effects extend beyond adolescence. METHOD: Data were obtained from the Christchurch Health and Development Study, a 35-year study of a longitudinal birth cohort. This investigation used generalized estimating equation modelling to estimate the associations between bullying victimization (ages 13-16 years) and psychotic symptoms (ages 18-35 years), before and after controlling for possible confounding factors, including: gender; childhood socio-economic status; child intelligence quotient; exposure to sexual abuse in childhood; anxious/withdrawn behaviour and attention problems (ages 7-9 years); and adolescent psychotic symptoms and paranoid ideation (ages 15-16 years). RESULTS: There was a significant (p < 0.0001) bivariate association between bullying victimization in adolescence and psychotic symptomatology in adulthood. Successive models controlling for covariation reduced this association to statistical non-significance. After controlling for covariates, those with the highest level of bullying victimization had rates of psychotic symptoms that were 1.21 (95% confidence interval 0.73-1.99) times higher than those who were not victimized. CONCLUSIONS: The association between bullying victimization in adolescence and psychotic symptomatology in adulthood could be largely explained by childhood behavioural problems, and exposure to sexual abuse in childhood. The results suggest that bullying victimization was unlikely to have been a cause of adult psychotic symptoms, but bullying victimization remained a risk marker for these symptoms.

Life-stress and reactivity by gender in a longitudinal birth cohort at 30 and 35 years.

PURPOSE: Previous literature has shown gender differences in reactivity to stressful life events. However, it is unclear whether gender differences in stress reactivity are consistent across a series of life event domains among longitudinal adult sample populations. METHODS: Data were gathered from the Christchurch Health and Development Study (CHDS). The CHDS is a longitudinal birth cohort of 1265 children born in 1977 in Christchurch, New Zealand. Cohort members were questioned on their experience of, and distress from, a series of life event domains (interpersonal problems; victimization; illness/death; pregnancy/parenthood; employment/finance problems) spanning two age-periods 25-30 years (data collected in 2007) and 30-35 years (data collected in 2012). The data were pooled across observations and analyzed using population-averaged repeated-measures regression methods. RESULTS: Overall, men and women reported experiencing similar numbers of life events for each domain. However, men reported more victimization and more employment/financial problems; women reported more illness/death events. Women reported experiencing more distress per life event for the domains of interpersonal problems, illness/death and pregnancy/parenthood. Men and women reported similar distress per life event for the victimization and employment/finance domains. The results were robust to control for: child and adolescent factors (childhood abuse exposure; adolescent personality; mental health) and adult factors (mental health; self-esteem). CONCLUSION: These findings are consistent with a growing body of evidence indicating that some life events including interpersonal problems, illness/death and pregnancy/parenthood may be intrinsically more distressing for women. Detection of life event distress is important to aid in the prevention of mental/physical health problems.

Exploring the feasibility of linking historical air pollution data to the Christchurch Health and Development study: A birth cohort study in Aotearoa, New Zealand.

Spatial life course epidemiological approaches offer promise for prospectively examining the impacts of air pollution exposure on longer-term health outcomes, but existing research is limited. An essential aspect, often overlooked is the comprehensiveness of exposure data across the lifecourse. The primary objective was to meticulously reconstruct historical estimates of air pollution exposure to include prenatal exposure as well as annual exposure from birth to 10 years (1977-1987) for each cohort member. We linked these data from a birth cohort of 1,265 individuals, born in Aotearoa/New Zealand in mid-1977 and studied to age 40, to historical air pollution data to create estimates of exposure from birth to 10 years (1977-1987). Improvements in air quality over time were found. However, outcomes varied by demographic and socioeconomic factors. Future research should examine how inequitable air pollution exposure is related to health outcomes over the life course.

Chlamydial infections in Chinese livestock.

The occurrence and impact of chlamydial infections in Western livestock is well documented in the international literature, but less is known aboutthese infections in livestock in the People's Republic of China. China's livestock production and its share in the global market have increased significantly in recent decades. In this review, the relevant English and Chinese literature on the epidemiology of chlamydial infections in Chinese livestock is considered, and biosecurity measures, prophylaxis and treatment of these infections in China's livestock are compared with Western practices. Chlamydial infections are highly prevalent in Chinese livestock and cause important economic losses, as they do in the rest of the world. Surveillance data and diagnostic results of abortion outbreaks in cattle, sheep and goats highlight the importance of virulent chlamydial infections in China's major ruminant species in many of China's provinces, autonomous regions and municipalities. Data from many of China's provincial divisions also indicate the widespread presence of chlamydial infections in industrially reared swine across the country. Less is known about chlamydial infections in yak, buffalo and horses, but available reports indicate a high prevalence in China's populations. In these reports, chlamydiosis was related to abortions in yak and pneumonia in horses. In Western countries, chlamydial infections are principally treated with antibiotics. In China, however, traditional medicine is often used in conjunction with antibiotics or used as an alternative treatment.

Child abuse and neglect and mental health outcomes in adulthood by ethnicity: Findings from a 40-year longitudinal study in New Zealand/Aotearoa.

BACKGROUND: Longitudinal studies consistently report adverse long-term outcomes of childhood maltreatment. Little is known about the impact of childhood maltreatment on mental health among a marginalized population (New Zealand Maori); therefore, we cannot assume the effects of maltreatment are the same across the population. OBJECTIVE: Associations were examined between childhood sexual abuse (CSA), childhood physical punishment (CPP) and childhood neglect (CN) (<16 years) and mental health outcomes 18-40 years, by ethnicity (Maori/non-Maori). PARTICIPANTS AND SETTING: Data from the Christchurch Health and Development Study, a study of a birth cohort of 1265 children born in Christchurch in 1977. By age 40, 17.8 % (n = 191) reported New Zealand Maori ethnic identity; 82.2 % (n = 883) were non-Maori. METHODS: CSA, CPP (<16 years) were measured at 18, 21 years; CN was measured at 40 years. Major depression, anxiety disorder, suicidal ideation, alcohol abuse/dependence and cannabis abuse/dependence were measured at ages 21, 25, 30, 35 and 40 years. Childhood confounding variables controlled. Analyses were extended to include Maori ethnicity. RESULTS: After statistical adjustment, experience of severe childhood maltreatment increased odds of mental health problems 1.8-2.6×, compared to no maltreatment; the effects of maltreatment were similar for males and females. For Maori, some higher rates of mental health problems were seen among those maltreated, no statistically significant associations were detected after Bonferroni correction (among severe maltreatment vs. no maltreatment). Limitations should be considered when interpreting results. CONCLUSIONS: Exposure to childhood maltreatment has long-term effects into middle-age. Further research employing culturally-sensitive approaches may help clarify Maori childhood maltreatment outcomes.

Outcomes for 236 patients from a 2-year early intervention in psychosis service.

OBJECTIVE: To examine: i) changes in key outcome measures over time in treatment in a representative first-episode psychosis treatment cohort and ii) baseline predictors of service disengagement. METHOD: Baseline characteristics of 236 patients were examined for associations with outcomes over time using generalized estimating equation models. The data on disengagement were analysed using logistic regression. RESULTS: After controlling for admission scores, patients showed consistently improved outcomes while in treatment on functional recovery (unemployment, P < 0.01; HoNOS, P < 0.001; the Quality of Life Scale, P < 0.001; GAF, P < 0.05) but not symptomatology (as assessed by the PANSS and substance abuse). The 64 (33%) who disengaged were more likely to be unemployed (P < 0.01) and have higher HoNOS (P < 0.01) and GAF (P < 0.05) scores at baseline. CONCLUSION: This evaluation has shown significant improvements in psychosocial functioning but not psychopathology during treatment at an Early Intervention for Psychosis Service. Despite attempts to retain patients, there is a high rate of treatment discontinuation.

Ablation of colorectal xenografts with combined radioimmunotherapy and tumor blood flow-modifying agents.

Radioimmunotherapy (RIT) does not readily eradicate common solid tumors and therefore requires augmentation by complementary therapies that do not increase normal tissue damage. We have examined the efficacy of RIT combined with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a drug which induces immunomodulation and cytokine production and preferentially reduces tumor blood flow, using a colorectal xenograft model in nude mice. Although an optimal i.p. dose (27.5 mg/kg) of drug alone induced massive hemorrhagic necrosis of all but a thin peripheral rim of viable tumor cells, survival was unaffected. However, when combined with i.v. 18.5 MBq 131I-labeled anti-carcinoembryonic antigen IgG, DMXAA significantly potentiated the RIT without increased toxicity, with five of six mice showing complete cures. Scheduling was critical because the antibody must be allowed to reach maximum tumor accumulation before initiation of drug-induced blood flow inhibition. Subsequently, the antibody was retained preferentially in the tumor, reaching approximately twice control levels by 5 days after drug delivery. In combined studies, the drug had a narrow therapeutic window, 30 mg/kg being toxic to two of six mice, whereas 20 mg/kg were ineffective. However, the addition of a second vasoactive agent, serotonin, to RIT plus 20 mg/kg DMXAA enhanced therapy without increasing systemic toxicity. Tumor histology and phosphor image plate analysis reflected these results. When given without RIT, the two drugs combined, although not alone, also significantly inhibited tumor growth. Drug-induced tumor necrosis and tumor retention of radioantibody may both contribute to the enhanced RIT produced by this combined complementary therapy.

Relation between age of first drinking and mental health and alcohol and drug disorders in adulthood: evidence from a 35-year cohort study.

AIMS: To estimate associations between age of first drinking (AFD) and alcohol use disorder, nicotine dependence, cannabis dependence, illicit drug dependence, major depression and anxiety disorder in adulthood, net of a series of covariate factors. DESIGN: Data were obtained from a longitudinal birth cohort. SETTING: Christchurch, New Zealand. PARTICIPANTS: The Christchurch Health Development Study (CHDS), a longitudinal study of a cohort born in 1977 and studied to age 35 years. Analysis samples ranged in size from 1056 (ages 11-13 years) to 962 (age 35 years); 50.2% of the total sample was male. MEASUREMENTS: A measure of AFD (ages 5-13+ years) was generated using latent class analysis. Outcome measures included: major depression, anxiety disorders, alcohol use disorder, nicotine dependence, cannabis dependence and other illicit drug dependence during the period 15-35 years. Covariate factors measured during childhood included family socio-economic status, family functioning, parental alcohol-related attitudes/behaviours and individual factors. FINDINGS: Earlier AFD was associated significantly (P < 0.05) with increased risk of later alcohol use disorders, nicotine dependence and illicit drug dependence, and was associated marginally (P < 0.10) with cannabis dependence, but not depression or anxiety disorder. After controlling for covariate factors, the associations between AFD and outcomes were no longer statistically significant [alcohol use disorder: B = -0.07, 95% confidence interval (CI) = -0.22, 0.08; nicotine dependence: B = -0.15, 95% CI = -0.34, 0.04; illicit drug dependence: B = -0.29, 95% CI = -0.73, 0.15; cannabis dependence: B = -0.05, 95% CI = -0.31, 0.22]. CONCLUSIONS: The associations between age of first drinking and later alcohol/drug disorders appear to be accounted for at least to some degree by factors related to characteristics of the individual and family during childhood.

Improved radioimmunodetection of tumours using liposome-entrapped antibody.

The discrimination of radioimmunodetection of tumours is reduced by the presence of circulating radiolabelled antibody (primary antibody). We have prepared liposomes containing an antibody to the primary antibody (secondary antibody), with the intention of complexing and delivering to the liver primary antibody which is not associated with the tumour. In mice bearing xenografts of human tumours which secrete the marker carcinoembryonic antigen (CEA), liposomally entrapped secondary antibody was able to reduce the blood levels of 125I-labelled anti-CEA within 2 h, without reducing the amount of anti-CEA bound to the tumour. We therefore suggest that the use of liposomally entrapped secondary antibody would improve the diagnostic potential of radioimmunodetection of tumours and their metastases.

Ablation of human choriocarcinoma xenografts in nude mice by antibody-directed enzyme prodrug therapy (ADEPT) with three novel compounds.

Three novel prodrugs have been designed for use as anticancer agents. Each is a bifunctional alkylating agent which has been protected to form a relatively inactive prodrug. They are designed to be activated to their corresponding alkylating agents at a tumour site by prior administration of an antitumour antibody conjugated to the bacterial enzyme carboxypeptidase G2 (CPG2) in a two-phase system called antibody-directed enzyme prodrug therapy (ADEPT). The Km and Vmax values for three different antibody-CPG2 conjugates were determined in relation to each prodrug. The Km values ranged from 4.5-12 mumol/l and the Vmax from 0.5-1.6 mumol/U/min. Athymic Nu/Nu mice with palpable transplanted human choriocarcinoma xenografts, which are resistant to conventional chemotherapy, were treated with anti-human chorionic gonadotropin antibodies conjugated to CPG2. This was followed by each of the three novel prodrugs. Significant increase in survival was obtained in three of the regimens tested using only one course of treatment. This demonstrates the potential of a tumour-localised bacterial enzyme to activate protected alkylating agents in order to eradicate an established human xenograft.

Relation of threatened egotism to violence and aggression: the dark side of high self-esteem.

Conventional wisdom has regarded low self-esteem as an important cause of violence, but the opposite view is theoretically viable. An interdisciplinary review of evidence about aggression, crime, and violence contradicted the view that low self-esteem is an important cause. Instead, violence appears to be most commonly a result of threatened egotism--that is, highly favorable views of self that are disputed by some person or circumstance. Inflated, unstable, or tentative beliefs in the self's superiority may be most prone to encountering threats and hence to causing violence. The mediating process may involve directing anger outward as a way of avoiding a downward revision of the self-concept.

Technetium-99m radiolabeling using a phage-derived single-chain Fv with a C-terminal cysteine.

UNLABELLED: Single-chain Fv (scFv) antibody fragments have potential for clinical imaging because of their rapid tumor penetration and high tumor-to-tissue ratios at early time points. ScFvs clear rapidly from the circulation so radiolabels such as 99mTc which have short half-lives are desirable, but the free thiol groups necessary for labeling with 99mTc are not normally found on these molecules. METHODS: We constructed a vector which enabled a free cysteine to be linked to the C-terminus of scFvs. MFE-23, a scFv directed against carcinoembryonic antigen (CEA), was cloned into this vector and cys-tagged MFE-23 was labeled with 99mTc using a D-glucarate transfer method. RESULTS: The radiolabeled product was stable in vivo and in vitro and showed favorable tumor-to-blood ratios in vivo at early time points (4:1 at 24 hr and 8:1 at 48 hr), although high kidney levels were also detected. CONCLUSION: Our study demonstrates an effective method to enable scFvs radiolabeling with 99mTc and also shows the potential of using a 99mTc-labeled scFv for clinical imaging studies.

Antibody directed enzyme prodrug therapy (ADEPT): a three phase system.

Monoclonal anti-CEA antibody, A5B7, and its fragments conjugated to CPG2 localize to a peak concentration in the LS174T xenografts within 24 h after injection, but enzyme activity persists in plasma such that prodrug injection has to be delayed for 5-6 days in order to avoid toxicity. Injection of prodrug at this time did not result in growth delay of this tumour. A three-phase system has been developed in which residual plasma enzyme was inactivated and cleared by a galactosylated anti-CPG2 antibody, SB43gal, allowing prodrug administration within 24 h after the conjugate. Using this three-phase system, a marked growth delay of this tumour was achieved after a single course of treatment consisting of conjugate injection followed by SB43gal, 19 h later and three doses of the prodrug.

Antibody directed enzyme prodrug therapy (ADEPT): clinical report.

Following an extensive series of studies in nude mice with human xenografts a pilot scale clinical trial of antibody directed enzyme prodrug therapy has been initiated. The principle is to activate a relatively inert prodrug to an active cytotoxin by a tumour located enzyme. In the first stage of the study a prodrug para-N-(mono-2-chloroethyl monomesyl)-aminobenzoyl glutamic acid was administered to six patients with advanced colorectal cancer in a dose escalating protocol. Nausea and vomiting occurred as the only discernible toxic effect at the higher dose levels. Three of these patients and two other patients with advanced disease have proceeded to the second stage of the study in which an antibody-enzyme conjugate was given IV, followed after 36-48 h by a galactosylated anti-enzyme antibody. When plasma enzyme levels had become undetectable the patients received multiple doses of the prodrug. At the lower doses toxicity was minimal as were clinical responses. Two patients received higher doses which resulted in myelosuppression and temporary regression of advanced disease. No complications resulted from administration of the antibody-enzyme complex or enzyme inactivating antibody. The myelosuppression is attributable to the relatively long half-life of the active drug formed from the prodrug used in the present study.

Biodistribution of an antibody-enzyme conjugate for antibody-directed enzyme prodrug therapy in nude mice bearing a human colon adenocarcinoma xenograft.

The enzyme carboxypeptidase G2 (CPG2) can be targeted to tumors by antibodies and used to activate prodrugs in a treatment called antibody-directed enzyme prodrug therapy (ADEPT). Different doses of CPG2 conjugated to the anti-CEA antibody A5B7 were administered i.v. to nude mice bearing the LS174T human colon adenocarcinoma xenograft, and the biodistribution of conjugate activity 48 and 72 h later was determined using a novel high-performance liquid chromatography (HPLC) method. Conjugate doses of 2,500 and 625 U/kg gave tumor enzyme levels of 0.5-0.6 U/g. Lower doses of 300 and 150 U/kg gave tumor enzyme levels of 0.1-0.3 U/g. Intriguingly, the best tumor:blood ratio of conjugate activity at both 48 and 72 h was achieved after administration of the 625-U/kg dose, not the 2,500-U/kg dose. After 48 h this ratio was 3.8, whereas after 72 h the value was 5.5. This conjugate dose also gave the greatest tumor:tissue ratios in all other tissues examined. After 72 h the tumor:colon ratio was 105, whereas the tumor:kidney ratio was 36. In ADEPT, to obtain maximal tumor damage to LS174T xenografts in nude mice with minimal systemic toxicity using the A5B7-CPG2 conjugate, prodrug should therefore be administered at least 72 h after a conjugate dose of 625 U/kg.

Simultaneous determination of inorganic anions and cations by capillary electrophoresis with indirect UV detection.

The development of a separation system for the simultaneous determination of inorganic anions and cations, low-molecular-mass organic acids and aliphatic amines by capillary electrophoresis with indirect UV detection using new electrolyte systems is described. Different principles of the experimental enforcement are compared. The principle of both-side injection was investigated using two different electrolyte systems. In order to avoid system peaks caused by the presence of different electrolyte co-ions, the selection of useful electrolyte components is more difficult than the choice of electrolytes for separate anion or cation analysis and special preparation procedures are necessary. The applicability of the method is shown by investigations of reproducibility, linearity of the calibration and by the analysis of drinking water including a comparison with results of measurements carried out with atomic absorption spectrometry for the cation determination, and ion chromatography for the anion determination.