From adolescence to parenthood: a multi-decade study of preconception mental health problems and postpartum parent-infant bonds.

PURPOSE: To examine associations between anxiety and depressive symptoms across adolescence and young adulthood with subsequent maternal- and paternal-infant bonding at 1 year postpartum. METHODS: The data were from a prospective, intergenerational cohort study. Participants (381 mothers of 648 infants; 277 fathers of 421 infants) self-reported depression and anxiety at three adolescent waves (ages 13, 15 and 17 years) and three young adult waves (ages 19, 23 and 27 years). Subsequent parent-infant bonds with infants were reported at 1 year postpartum (parent age 29-35 years). Generalised estimating equations (GEE) separately assessed associations for mothers and fathers. RESULTS: Mean postpartum bonding scores were approximately half a standard deviation lower in parents with a history of persistent adolescent and young adult depressive symptoms (maternal ßadj = - 0.45, 95% CI - 0.69, - 0.21; paternal ßadj = - 0.55, 95% CI - 0.90, 0.20) or anxiety (maternal ßadj = - 0.42, 95% CI - 0.66, - 0.18; paternal ßadj = - 0.49, 95% CI - 0.95, 0.03). Associations were still mostly evident, but attenuated after further adjustment for postpartum mental health concurrent with measurement of bonding. CONCLUSIONS: Persistent symptoms of depression or anxiety spanning adolescence and young adulthood predict poorer emotional bonding with infants 1-year postbirth for both mothers and fathers.

Psychosocial predictors of binge-drinking residual harm in adolescence and young adulthood: Findings from the Australian Temperament Project.

AIMS: We examine the extent to which adolescent and young adult psychosocial factors are associated with variation in the experience of common types of harm (e.g., injuries, violence, sexual regrets) with respect to binge-drinking frequency - termed residual harm. METHODS: Data were from the Australian Temperament Project, a population-based cohort study that has followed a sample of young Australians from infancy to adulthood since 1983. The current sample comprised 1,081 (565 women). Residual harm was operationalised by saving residuals from models regressing number of alcohol harms onto binge-drinking frequency at each of 5 waves, two in adolescence (15-16 and 17-18 years) and three in young adulthood (19-20, 23-24, and 27-28 years). Psychosocial factors (mental health, social skills, quality of parent and peer relationships) were assessed prior to binge drinking in early adolescence (13-14 years) and then again in young adulthood (19-20 years). RESULTS: Adolescent predictors of decreased residual harm were lower depressive symptoms, and higher cooperation, self-control, and peer and parent attachment. Young adult predictors of decreased residual harm were lower depressive, anxiety, and stress symptoms and peer and parent negative appraisal, and higher responsibility, and peer and parent emotional support. Associations were evident in males and females, although the strength of some associations diminished with age. CONCLUSIONS: Adolescents and young adults with better mental health, social skills, and relationship quality experienced less harm with respect to their binge-drinking frequency. Future research should examine the potential of investment in strength-based interventions for young people.

Childhood disadvantage and adolescent socioemotional wellbeing as predictors of future parenting behaviour.

INTRODUCTION: In extending work on early life antecedents of parenting, we investigate associations between childhood family history of disadvantage, adolescent socioemotional wellbeing, and age at first parenthood and subsequent parenting behaviour. METHODS: Parent-child interactions were recorded when participants in the longitudinal Dunedin Multidisciplinary Health and Development Study (New Zealand) had a three-year-old child. Data were available for 358 mothers and 321 fathers, aged between 17.7 and 41.5 at the time of their child's birth. Associations between parenting and antecedent data on socioeconomic disadvantage, adolescent wellbeing and mental health, as well as current adult mental health and age at parenting, were tested for using structural equation modelling. RESULTS: Family disadvantage in childhood and lower adolescent wellbeing was associated with less positive future parenting, but only adult (not adolescent) anxiety/depression symptoms were directly associated with parenting behaviour. Childhood family disadvantage was associated with further disadvantage across the life course that included less positive parenting of the next generation. In contrast, socioemotional wellbeing during adolescence and later age of onset of parenting were associated with more positive parenting. CONCLUSIONS: Reducing childhood disadvantage and improving socioemotional wellbeing during childhood and adolescence is likely to have intergenerational benefits through better parenting of the next generation.

Exploring a causal model in observational cohort data: The role of parents and peers in shaping substance use trajectories.

AIMS: To explore the process of applying counterfactual thinking in examining causal determinants of substance use trajectories in observational cohort data. Specifically, we examine the extent to which quality of the parent-adolescent relationship and affiliations with deviant peers are causally related to trajectories of alcohol, tobacco, and cannabis use across adolescence and into young adulthood. METHODS: Data were drawn from the Australian Temperament Project, a population-based cohort study that has followed a sample of young Australians from infancy to adulthood since 1983. Parent-adolescent relationship quality and deviant peer affiliations were assessed at age 13-14 years. Latent curve models were fitted for past month alcohol, tobacco, and cannabis use (n = 1590) from age 15-16 to 27-28 years (5 waves). Confounding factors were selected in line with the counterfactual framework. RESULTS: Following confounder adjustment, higher quality parent-adolescent relationships were associated with lower baseline cannabis use, but not alcohol or tobacco use trajectories. In contrast, affiliations with deviant peers were associated with higher baseline binge drinking, tobacco, and cannabis use, and an earlier peak in the cannabis use trajectory. CONCLUSIONS: Despite careful application of the counterfactual framework, interpretation of associations as causal is not without limitations. Nevertheless, findings suggested causal effects of both parent-adolescent relationships and deviant peer affiliations on the trajectory of substance use. Causal effects were more pervasive (i.e., more substance types) and protracted for deviant peer affiliations. The exploration of causal relationships in observational cohort data is encouraged, when relevant limitations are transparently acknowledged.

A comparison of longitudinal modelling approaches: Alcohol and cannabis use from adolescence to young adulthood.

BACKGROUND: Modelling trajectories of substance use over time is complex and requires judicious choices from a number of modelling approaches. In this study we examine the relative strengths and weakness of latent curve models (LCM), growth mixture modelling (GMM), and latent class growth analysis (LCGA). DESIGN: Data were drawn from the Australian Temperament Project, a 36-year-old community-based longitudinal study that has followed a sample of young Australians from infancy to adulthood across 16 waves of follow-up since 1983. Models were fitted on past month alcohol use (n = 1468) and cannabis use (n = 549) across six waves of data collected from age 13-14 to 27-28 years. FINDINGS: Of the three model types, GMMs were the best fit. However, these models were limited given the variance of numerous growth parameters had to be constrained to zero. Additionally, both the GMM and LCGA solutions had low entropy. The negative binomial LCMs provided a relatively well-fitting solution with fewer drawbacks in terms of growth parameter estimation and entropy issues. In all cases, model fit was enhanced when using a negative binomial distribution. CONCLUSIONS: Substance use researchers would benefit from adopting a complimentary framework by exploring both LCMs and mixture approaches, in light of the relative strengths and weaknesses as identified. Additionally, the distribution of data should inform modelling decisions.

The natural history of risky drinking and associated harms from adolescence to young adulthood: findings from the Australian Temperament Project.

BACKGROUND: We aimed to describe the natural history of heavy episodic drinking (HED) and associated harms from adolescence to young adulthood in a large Australian population cohort study. METHOD: The Australian Temperament Project consists of mothers and babies (4-8 months) recruited from Infant Welfare Centres and followed every 2 to 4 years until age 28 years. Analyses were based on data from 1156 young people (497 male; 659 female) surveyed repeatedly at ages 16, 18, 20, 24 and 28 years. We used dual processes latent class growth analysis to estimate trajectories of HED and associated harms, employing a piecewise approach to model the hypothesized rise and subsequent fall across adolescence and the late twenties, respectively. RESULTS: We identified four sex-specific trajectories and observed little evidence of maturing-out across the twenties. In males, a normative pattern of increasing HED across the twenties with little related harm was observed (40% of the male sample). Early and late starter groups that peaked in harms at age 20 years with only minor attenuation in binging thereafter were also observed (6.1% and 35%, respectively). In females, a normative pattern of increasing, but moderate, HED with little related harm was observed (44% of the female sample). Early and late starter groups were also identified (18% and 17%, respectively); however, unlike males, the female late starter group showed a pattern of increasing HED and related harms. CONCLUSIONS: Continued patterns of risky alcohol use and related harms are apparent for both males and females across the twenties.

The natural history of internalizing behaviours from adolescence to emerging adulthood: findings from the Australian Temperament Project.

BACKGROUND: The aims of the study were to describe the patterning and persistence of anxiety and depressive symptoms from adolescence to young adulthood and to examine long-term developmental relationships with earlier patterns of internalizing behaviours in childhood. METHOD: We used parallel processes latent growth curve modelling to build trajectories of internalizing from adolescence to adulthood, using seven waves of follow-ups (ages 11-27 years) from 1406 participants of the Australian Temperament Project. We then used latent factors to capture the stability of maternal reported child internalizing symptoms across three waves of early childhood follow-ups (ages 5, 7 and 9 years), and examined relationships among these patterns of symptoms across the three developmental periods, adjusting for gender and socio-economic status. RESULTS: We observed strong continuity in depressive symptoms from adolescence to young adulthood. In contrast, adolescent anxiety was not persistent across the same period, nor was it related to later depressive symptoms. Anxiety was, however, related to non-specific stress in young adulthood, but only moderately so. Although childhood internalizing was related to adolescent and adult profiles, the associations were weak and indirect by adulthood, suggesting that other factors are important in the development of internalizing symptoms. CONCLUSIONS: Once established, adolescent depressive symptoms are not only strongly persistent, but also have the potential to differentiate into anxiety in young adulthood. Relationships with childhood internalizing symptoms are weak, suggesting that early adolescence may be an important period for targeted intervention, but also that further research into the childhood origins of internalizing behaviours is needed.

Association between serotonin transporter genotype, brain structure and adolescent-onset major depressive disorder: a longitudinal prospective study.

The extent to which brain structural abnormalities might serve as neurobiological endophenotypes that mediate the link between the variation in the promoter of the serotonin transporter gene (5-HTTLPR) and depression is currently unknown. We therefore investigated whether variation in hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex volumes at age 12 years mediated a putative association between 5-HTTLPR genotype and first onset of major depressive disorder (MDD) between age 13-19 years, in a longitudinal study of 174 adolescents (48% males). Increasing copies of S-alleles were found to predict smaller left hippocampal volume, which in turn was associated with increased risk of experiencing a first onset of MDD. Increasing copies of S-alleles also predicted both smaller left and right medial OFC volumes, although neither left nor right medial OFC volumes were prospectively associated with a first episode of MDD during adolescence. The findings therefore suggest that structural abnormalities in the left hippocampus may be present prior to the onset of depression during adolescence and may be partly responsible for an indirect association between 5-HTTLPR genotype and depressive illness. 5-HTTLPR genotype may also impact upon other regions of the brain, such as the OFC, but structural differences in these regions in early adolescence may not necessarily alter the risk for onset of depression during later adolescence.

The role of parental alcohol use, parental discipline and antisocial behaviour on adolescent drinking trajectories.

BACKGROUNDS: Parental drinking, harsh parental discipline and adolescent antisocial behaviour have been independently implicated in adolescent alcohol use. Robust prospective studies are required to examine developmental relationships between these factors and their effect on trajectories of alcohol use across adolescence. METHODS: Data were ascertained at three consecutive adolescent waves (13.5, 15.5 and 17.5 years) from the Australian Temperament Project, a 15-wave (30 year) general population birth cohort in Victoria, Australia. Adolescent alcohol trajectories, adjusted for time-varying measures of parenting and antisocial behaviour, were regressed on time-stable measures of parental alcohol use. The full case analysis comprised 751 individuals with complete data. RESULTS: Two distinct alcohol trajectories were identified across the three adolescent waves after adjusting for time-varying factors: a higher and lower drinking group. Both trajectories increased linearly over the study period. Antisocial behaviour was positively associated with both trajectories while harsh parental discipline was positively associated with alcohol use in the lower-use group only. Increased maternal and paternal drinking at 13.5 years placed teenagers at a greater risk of being included in the high-risk trajectory. CONCLUSION: Parental drinking was the strongest predictor of different drinking trajectories in adolescence. This finding underscores the importance of comprehensive public heath approaches that target both parental and adolescent drinking attitudes and behaviour.

A role for the DRD4 exon III VNTR in modifying the association between nicotine dependence and neuroticism.

INTRODUCTION: Neurotic psychopathology has been extensively examined as a risk factor for nicotine dependence (ND). Genetic stratification may partially explain variability in risk estimates. Genetic variants that compromise dopaminergic neurotransmission may motivate exposure to dopamine-stimulating agents, including nicotine. The 7-repeat allele of a Variable Number Tandem Repeat (VNTR) polymorphism in DRD4 (and evolutionary derivatives 5, 6, and 8 repeats; 7R+) is associated with reduced dopamine receptor function. The purpose of this study was to examine association between both smoking initiation (SI) and progression to ND by young adulthood and (a) history of neuroticism during adolescence, (b) DRD4 7R+, and (c) interaction between neuroticism and DRD4 7R+. METHODS: Participants were drawn from the Victorian Adolescent Health Cohort Study, a longitudinal study of the health and well-being of young Australians across 8 waves (14-24 years). Neuroticism was measured at Waves 3 and 6 (mean 15.9 and 17.4 years). SI was defined as any smoking at any wave. ND was measured at Wave 8 (mean 24.1 years). Genotype data for the DRD4 VNTR were available for 839 participants. RESULTS: While adolescent neuroticism was associated with SI, evidence for association with progression to ND was weak. However, there was evidence of interaction between neuroticism and DRD4 7R+: The odds of progression to ND among those with a history of neuroticism were more than 3.5-fold higher among 7R+ carriers. CONCLUSIONS: Without considering stratification by 7R+, the association between progression to ND and neuroticism would have been assumed barely significant. However, among those carrying DRD4 7R+, risk of progression was considerably intensified.

Patterns of adolescent smoking and later nicotine dependence in young adults: a 10-year prospective study.

OBJECTIVES: There is considerable variability in progression from smoking initiation to established smoking. This paper addresses the extent to which different patterns of adolescent smoking, including periods of cessation, predict smoking status in young adults. STUDY DESIGN: Ten-year, eight-wave prospective cohort study of a state-wide community sample in Victoria, Australia. METHODS: Participants were 1520 students from 44 secondary schools, initially aged 14 to 15 years. Adolescent smoking and quitting patterns were assessed during Waves 1-6 with self-reported frequency of use and a 7-day retrospective diary. The Fagerstrom Test for Nicotine Dependence (ND) was used to assess ND at the age of 24 years (Wave 8). RESULTS: The prevalence of ND in young adults was 16.9% for all adolescent smokers, with prevalence rates of 6.8% and 26.7% for adolescent non-daily and daily adolescent smokers, respectively. Maximum smoking levels, onset of daily smoking, duration of smoking, escalation time and duration of cessation during adolescence predicted later ND. Daily smokers who ceased smoking for at least two waves (> or = 12 months) had a level of risk similar to adolescents who had never smoked. CONCLUSIONS: Quitting smoking as an adolescent substantially alters the risk for later ND. For adolescents who become daily smokers, quitting for 12 months should be the aim in tobacco control and clinical interventions.

Prospects for epigenetic research within cohort studies of psychological disorder: a pilot investigation of a peripheral cell marker of epigenetic risk for depression.

Cohort studies have considerable prima facie value for investigating epigenetic processes in psychological disorder; however, the future prospects for such studies will depend on valid peripheral markers. The purpose of this pilot study was to investigate association between buccal cell methylation and risk for depression. Epigenotyping was limited to promoter methylation of the serotonin transporter gene (5HTT). A transcription limiting VNTR in the 5HTT promoter (5HTTLPR) was also genotyped. A nested sample of 25 depressed and 125 non-depressed adolescents was drawn from an established longitudinal study of adolescent health. There was no association between depressive symptoms and either buccal cell 5HTT methylation or 5HTTLPR. However, depressive symptoms were more common among those with elevated buccal cell 5HTT methylation who carried 5HTTLPR short-allele (OR 4.9, CI 1.9-13, p=0.001). Both complete and partial (as little as 10%) methylation of a 5HTT reporter gene in an expressing cell line reduced 5HTT activity. Replication is needed.

COMT Val(158)Met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence: results from the Victorian Adolescent Health Cohort Study.

We investigated whether a composite genetic factor, based on the combined actions of catechol-O-methyltransferase (COMT) (Val(158)Met) and serotonin transporter (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight-wave longitudinal study of mental health and well-being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose-response reductions in the odds of reporting persisting generalized (free-floating) anxiety across adolescence were observed for the COMT Met(158) [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76-0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79-0.99, P = 0.033). There was no evidence for a dose-response interaction effect between loci. However, there was a double-recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29-0.70, P < 0.001) among carriers homozygous for both the COMT Met(158) and the 5HTTLPR Short alleles (Met(158)Met + Short-Short) compared with the remaining cohort. The double-recessive effect remained after multivariate adjustment for a range of psychosocial predictors of anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.

Health-risk behaviours among adolescent survivors of childhood cancer.

BACKGROUND: The purpose of the study was to investigate smoking, alcohol use, illicit drug use and sexual risk taking among adolescent survivors of childhood cancer treated in Australia. PROCEDURE: A comparison study selecting on exposure (cancer vs. healthy) and administering a branched computerised questionnaire assessing health-risk behaviour, predominately by telephone interview. One hundred fifty-three adolescent survivors of childhood cancer were compared with age matched healthy adolescents drawn from one of two Australian population based surveys of adolescent health. Behaviours assessed were tobacco use, alcohol use, binge drinking, cannabis use, pain reliever use, other illicit drug use and unprotected sex. RESULTS: Compared to their healthy peers, younger survivors (13- to 17-years) were at an increased risk of reporting pain reliever use (OR = 2.1) for non-medical purposes, but lower risk of binge drinking (OR = 0.20), cannabis use (OR = 0.25), other illicit drug use (OR = 0.31), tobacco use (OR = 0.38) and alcohol use (OR = 0.44). Older survivors (18- to 24-years) were at an increased risk of reporting alcohol use (OR 1.5), but at lower risk of reporting cannabis use (OR = 0.27), other illicit drug use (OR = 0.44) and tobacco use (OR = 0.47). Survival analysis using the full adolescent survivor cohort (13- to 24-years) showed that the age of onset of tobacco use was later for cancer survivors (hazard ratio HR = 0.65). CONCLUSION: Adolescent cancer survivors show reduced involvement in most health-risk behaviours, with the exception of pain reliever use among younger survivors and alcohol use among the older survivors. Although risks were reduced a substantial proportion of survivors engage in these behaviours.

Association between 5-HTTLPR genotypes and persisting patterns of anxiety and alcohol use: results from a 10-year longitudinal study of adolescent mental health.

The serotonin transporter gene (5-HTT) encodes a transmembrane protein that plays an important role in regulating serotonergic neurotransmission and related aspects of mood and behaviour. The short allele of a 44 bp insertion/deletion polymorphism (S-allele) within the promoter region of the 5-HTT gene (5-HTTLPR) confers lower transcriptional activity relative to the long allele (L-allele) and may act to modify the risk of serotonin-mediated outcomes such as anxiety and substance use behaviours. The purpose of this study was to determine whether (or not) 5-HTTLPR genotypes moderate known associations between attachment style and adolescent anxiety and alcohol use outcomes. Participants were drawn from an eight-wave study of the mental and behavioural health of a cohort of young Australians followed from 14 to 24 years of age (Victorian Adolescent Health Cohort Study, 1992 - present). No association was observed within low-risk attachment settings. However, within risk settings for heightened anxiety (ie, insecurely attached young people), the odds of persisting ruminative anxiety (worry) decreased with each additional copy of the S-allele (approximately 30% per allele: OR 0.77, 95% CI 0.62-0.97, P=0.029). Within risk settings for binge drinking (ie, securely attached young people), the odds of reporting persisting high-dose alcohol consumption (bingeing) decreased with each additional copy of the S-allele (approximately 35% per allele: OR 0.74, 95% CI 0.64-0.86, P<0.001). Our data suggest that the S-allele is likely to be important in psychosocial development, particularly in those settings that increase risk of anxiety and alcohol use problems.

Family risk factors for cannabis use: a population-based survey of Australian secondary school students.

The objective of this study was to investigate relationships between adolescent cannabis use and indices of parent - child attachment, family functioning and parent attitudes to drugs and delinquency. A total of 2848 year 9 and 2363 year 11 students participated in the Victorian Adolescent Health and Well-Being Survey (1999). The study was a school-based random sample of 535 metropolitan and rural, government and non-government secondary schools throughout Victoria, Australia. Cannabis use was defined as 'any' and 'weekly' use in the last 30 days. Multivariate logistic regression was used to identify independent associations between cannabis use and parent - child attachment, family functioning and parent attitudes to drugs and delinquency. Cannabis use in year 9 was associated with permissive parent attitudes to drugs and delinquency (any use: adjusted odds ratio (OR) = 8.1; weekly use: adjusted OR = 7.6), and was particularly sensitive to small changes in the quality of the parent - child relationship with risk increasing threefold for those describing their attachment as 'good' compared with 'very good' (any use: adjusted OR = 2.8, weekly use adjusted OR = 2.9). A similar, but more moderate pattern association was evident in year 11. After adjusting for other family and background factors, poor family functioning showed minimal association with level of cannabis use at both year levels. Results suggest that intervention efforts might sensibly target strengthening parent - children relationships and promoting less permissive parent attitudes to drug use.

Adolescent chronic illness: a qualitative study of psychosocial adjustment.

INTRODUCTION: The purpose of this study was to investigate the psychosocial issues facing young people living with a chronic medical condition. MATERIALS AND METHODS: Subjects were young people with a range of medical conditions who were on a waiting list to participate in the Chronic Illness Peer Support programme at the Centre for Adolescent Health, Royal Children's Hospital, Melbourne, Australia. Young people agreed to in-depth interviews which were taped and transcribed. Thematic analysis was undertaken by two researchers working independently. RESULTS: Thirty-five young people were interviewed. Thematic analysis revealed five broad themes: control (in control, under control, out of control); emotional reactions (happiness, frustration, anger, sadness, anxiety); acceptance (of illness, of others, of self); coping strategies, and; a search for meaning. The importance of social connections was emphasised. While illustrating the difficulties of managing a chronic medical condition during adolescence, a generally positive message emerges about these young people. CONCLUSIONS: Many young people with chronic illness appear relatively resilient in the face of the adjustment challenges presented by their illness. Interventions that allow a young person to explore meaning, build self-esteem, and acceptance through positive social connections are likely to improve adjustment outcomes in this group.

Efeitos de um implante de acetato de nomegestrol, um derivado de 19-nor-progesterona, na função tireoidiana / Effects of an implant of nomegestrol acetate, a 19-nor-progesterone derivative, on thyroid function

Este estudo foi realizado para avaliar tri-iodotironina (T3), tiroxina (T4), hormônio estimulante da tireóide (TSH), T3 uptake, T3 livre e T4 livre em usuárias do implante de acetato de nomegestrol (Uniplant). Dezoito voluntárias em idade reprodutiva, que desejavam fazer anticoncepção, foram recrutadas para o estudo e investigadas antes do início do tratamento. Amostras de sangue foram obtidas antes da inserção do implante, para análises hormonais. Em seguida, amostras de sangue foram colhidas 3,6,12 e 24 meses após a inserção do Uniplant. Todas as pacientes usaram contraceptivo não hormonal por um período mínimo de 6 meses, antes da inserção do implante. Os resultados observados no estudo mostraram que não houve diferença significante na tri-iodotironina (T3), tiroxina (T4) e hormônio estimulante da tireóide (TSH), durante dois anos de uso do Uniplant. Nenhuma diferença significante foi encontrada nos níveis de T3 livre, durante dois anos de uso do Uniplant. Um decréscimo significante foi abservado no T3 uptake (p<0,05) no 24º mês e no T4 livre (p<0,05) no 3º mês de uso do Uniplant. todas as alterações observadas no estudo foram inconsistentes e todos os níveis estavam dentro dos limites normais.

Salvage cryotherapy using an argon based system for locally recurrent prostate cancer after radiation therapy: the Columbia experience.

PURPOSE: Cryosurgical ablation of the prostate has been reported as potential treatment for radioresistant clinically localized prostate cancer. We report our experience with the safety and efficacy of salvage cryosurgery using the argon based CRYOCare system (Endocare, Inc, Irvine, California). MATERIALS AND METHODS: Between October 1997 and September 2000, 38 men with a mean age of 71.9 years underwent salvage cryosurgery for recurrent prostate cancer after radiation therapy failed. All patients had biochemical disease recurrence, defined as an increase in prostate specific antigen (PSA) of greater than 0.3 ng./ml. above the post-radiation PSA nadir. Subsequently prostate biopsy was positive for cancer. Pre-cryosurgery bone scan demonstrated no evidence of metastatic disease. In addition, these patients received 3 months of neoadjuvant androgen deprivation therapy before cryotherapy. RESULTS: The PSA nadir was 0.1 or less, 1 or less and greater than 1 ng./ml. in 31 (81.5%), 5 (13.2%) and 2 (5.3%) patients, respectively. Biochemical recurrence-free survival calculated from Kaplan-Meier curves was 86% at 1 year and 74% at 2 years. Reported complications included rectal pain in 39.5% of cases, urinary tract infection in 2.6%, incontinence in 7.9%, hematuria in 7.9% and scrotal edema in 10.5%. The rate of rectourethral fistula, urethral sloughing and urinary retention was 0%. CONCLUSIONS: Our study supports cryosurgery of the prostate as safe and effective treatment in patients in whom radiation therapy fails. Using the CRYOCare machine resulted in a marked decrease in complications.

Prostatic expression of hensin, a protein implicated in epithelial terminal differentiation.

OBJECTIVES: Hensin induces terminal differentiation in rabbit kidney collecting tubule cells. Rabbit hensin and human DMBT1 result from alternative splicing of the same gene. The human DMBT1 gene is located on chromosome 10q25-26, a region often deleted in prostate cancer. In this study we examined the potential role of this gene in terminal differentiation of prostate, as well as its role in prostatic carcinogenesis. METHODS: We searched for deletions of this gene in prostatic cells cultured from cancer and benign tissues using PCR and cDNA cloning. The expression of hensin/DMBT1 in cultured cells and during prostate development was characterized by immunochemistry. RESULTS: No deletions of hensin/DMBT1 similar to those found in glioblastomas, lung and esophageal cancers were observed in prostate cancer or BPH cells. Hensin/DMBT1 protein was localized in intracellular vesicles of epithelial cells in neonatal and 6-week-old mouse prostates. By 6 weeks, hensin/DMBT1 began to localize in the basal lamina of the prostate and vas deferens. In matured 6-month-old prostates, there was extensive deposition of hensin/DMBT1 in the basal lamina. CONCLUSIONS: There is no evidence that hensin/DMBT1 is implicated in prostatic carcinogenesis. The localization of hensin/DMBT1 during maturation raises the possibility that hensin/DMBT1 is involved in terminal differentiation of the prostate and vas deferens.