A comparison of characteristics of Kevorkian euthanasia cases and physician-assisted suicides in Oregon.

PURPOSE: The sociodemographic and clinical characteristics of Kevorkian euthanasia cases were compared with Oregon physician-assisted suicide (PAS) cases and U.S. mortality data. DESIGN AND METHODS: Two hundred variables were coded from medical examiner reports on all 69 Kevorkian euthanasia cases who died and were autopsied by the Oakland County Medical Examiner. Data on the 43 Oregon PAS cases in the first two years and U.S. mortality data were obtained from published sources. RESULTS: Only 25% of patients euthanized by Kevorkian were terminally ill as compared to 100% of Oregon PAS cases. PAS cases were significantly more likely to have cancer (72%) than euthanasia cases (29%). Women and those who were divorced or had never married were significantly more likely to seek euthanasia than would have been predicted by national mortality statistics. IMPLICATIONS: Gender and marital status appeared to influence decisions to seek an assisted death, and research on the role of these factors in end-of-life decision making is merited.

Mammary tumor induction and premature ovarian failure in ApcMin mice are not enhanced by Brca2 deficiency.

Inherited BRCA2 mutations predispose individuals to breast cancer and increase risk at other sites. Recent studies have suggested a role for the APC I1307K allele as a low-penetrance breast cancer susceptibility gene that enhances the phenotypic effects of BRCA1 and BRCA2 mutations. To model the consequences of inheriting mutant alleles of the BRCA2 and APC tumor suppressor genes, we examined tumor outcome in C57BL/6 mice with mutations in the Brca2 and Apc genes. We hypothesized that if the Brca2 and Apc genes were interacting to influence mammary tumor susceptibility, then mammary tumor incidence and/or multiplicity would be altered in mice that had inherited mutations in both genes. Female and male offspring treated with a single IP injection of 50 mg/kg N-ethyl-N-nitrosourea (ENU) at 35 days of age developed mammary adenoacanthomas by 100 days of age. The female Apc-mutant and Brca2/Apc double-mutant progeny had mean mammary tumor multiplicities of 6.7+/-2.8 and 7.2+/-2.7, respectively, compared to wild-type and Brca2-mutant females, which had mean mammary tumor multiplicities of 0.1+/-0.4 and 0.3+/-0.5, respectively. Female ENU-treated Apc-mutant and Brca2/Apc double heterozygotes were also susceptible to premature ovarian failure. Thus, the inheritance of an Apc mutation predisposes ENU-treated female and male mice to mammary tumors and, in the case of female mice, to ovarian failure. These results indicate that mammary tumor development in Apc-mutant mice can progress independently of ovarian hormones. The Apc mutation-driven phenotypes were not modified by mutation of Brca2, perhaps because Brca2 acts in a hormonally dependent pathway of mammary carcinogenesis.

A comparison of antecedents of homicide-suicide and suicide in older married men.

The authors compared characteristics of 27 older men who perpetrated a spousal homicide-suicide and 36 age-matched married men who committed suicide in west central Florida between 1988 and 1994. Data were collected as part of an ongoing retrospective study of homicide and suicide among older adults in Florida. Men who committed suicide had significantly more disease conditions than homicide-suicide perpetrators (P<0.0001). Half of the latter were in caregiving roles, vs. 17% of the suicides (chi(2)=5.40; P=0.027). Depression was a prominent premorbid feature of both groups, but none of the perpetrators tested positive for antidepressants postmortem.

Targeting adolescent mothers with depressive symptoms for early intervention.

Infants of mothers with depressive symptoms show developmental delays if symptoms persist over the first 6 months of the infant's life, thus highlighting the importance of identifying those mothers for early intervention. In Study 1, mothers with depressive symptoms (n = 160) and mothers without depressive symptoms (n = 100) and their infants were monitored to identify variables from the first 3 months that predict which mothers would still be symptomatic at 6 months. A "dysregulation" profile was noted for the infants of depressed mothers, including lower Brazelton scores, more indeterminate sleep, and elevated norepinephrine, epinephrine, and dopamine levels at the neonatal period, and greater right frontal EEG activation, lower vagal tone, and negative interactions at the 3- and 6-month periods. A group of maternal variables from the neonatal and 3-month assessments accounted for 51% of the variance in the mothers' continuing depressive symptoms. These variables included greater right frontal EEG activation, lower vagal tone, and less positive interactions at 3 months, and elevated norepinephrine, serotonin, and cortisol levels at the neonatal stage. In Study 2, a similar sample of mothers with depressive symptoms (n = 160) and without depressive symptoms (n = 100) was recruited and followed to 3 months. Those symptomatic mothers who had values above (or below) the median (depending on the negative direction) on the predictor variables identified in Study 1 (taken from the first 3 months) were then randomly assigned to an intervention or a control group at 3 months. These groups were then compared with each other, as well as with the group without depressive symptoms, at 6 and 12 months. The intervention, conducted from 3 to 6 months, consisted of free day care for the infants and a rehab program (social, educational, and vocational) plus several mood induction interventions for the mothers, including relaxation therapy, music mood induction, massage therapy, and mother-infant interaction coaching. Although the mothers who received the intervention continued to have more depressive symptoms than did the nondepressed mothers, their interactions significantly improved and their biochemical values and vagal tone normalized. Their infants also showed more positive interations, better growth, fewer pediatric complications, and normalized biochemical values, and by 12 months their mental and motor scores were better than those of the infants in the control group.

BRCA2-null embryonic survival is prolonged on the BALB/c genetic background.

Women who inherit mutations in the BRCA2 cancer susceptibility gene have an 85% chance of developing breast cancer. The function of the BRCA2 gene remains elusive, but there is evidence to support its role in transcriptional transactivation, tumor suppression, and the maintenance of genomic integrity. Individuals with identical BRCA2 mutations display a different distribution of cancers, suggesting that there are low-penetrance genes that can modify disease outcome. We hypothesized that genetic background could influence embryonic survival of a Brca2 mutation in mice. Brca2-null embryos with a 129/SvEv genetic background (129(B2-/-)) died before embryonic day 8. 5. Transfer of this Brca2 mutation onto the BALB/cJ genetic background (BALB/c(B2-/-)) extended survival to embryonic day 10.5. These results indicate that the BALB/c background harbors genetic modifiers that can prolong Brca2-null embryonic survival. The extended survival of BALB/c(B2-/-) embryos enabled us to ask whether transcriptional regulation of the Brca1 and Brca2 genes is interdependent. The interdependence of Brca1 and Brca2 was evaluated by studying Brca2 gene expression in BALB/c(B1-/-) embryos and Brca1 gene expression in BALB/c(B2-/-) embryos. Nonisotopic in situ hybridization demonstrated that Brca2 transcript levels were comparable in BALB/c(B1-/-) embryos and wild-type littermates. Likewise, reverse transcriptase-polymerase chain reactions confirmed Brca1 mRNA expression in embryonic day 8.5 BALB/c(B2-/-) embryos that was comparable to Brca2-heterozygous littermates. Thus, the Brca1 and Brca2 transcripts are expressed independently of one another in Brca1- and Brca2-null embryos. Mol. Carcinog. 28:174-183, 2000.

Mice heterozygous for a Brca1 or Brca2 mutation display distinct mammary gland and ovarian phenotypes in response to diethylstilbestrol.

Women who inherit mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2, are predisposed to the development of breast and ovarian cancer. We used mice with a Brca1 mutation on a BALB/cJ inbred background (BALB/cB1+/- mice) or a Brca2 genetic alteration on the 129/SvEv genetic background (129B2+/- mice) to investigate potential gene-environment interactions between defects in these genes and treatment with the highly estrogenic compound diethylstilbestrol (DES). Beginning at 3 weeks of age, BALB/cB1+/-, 129B2+/-, and wild-type female mice were fed a control diet or a diet containing 640 ppb DES for 26 weeks. DES treatment caused vaginal epithelial hyperplasia and hyperkeratosis, uterine inflammation, adenomyosis, and fibrosis, as well as oviductal smooth muscle hypertrophy. The severity of the DES response was mouse strain specific. The estrogen-responsive 129/SvEv strain exhibited an extreme response in the reproductive tract, whereas the effect in BALB/cJ and C3H/HeN(MMTV-) mice was less severe. The Brca1 and Brca2 genetic alterations influenced the phenotypic response of BALB/cJ and 129/SvEv inbred strains, respectively, to DES in the mammary gland and ovary. The mammary duct branching morphology was inhibited in DES-treated BALB/cB1+/- mice compared with similarly treated BALB/cB1+/+ littermates. In addition, the majority of BALB/cB1+/- mice had atrophied ovaries, whereas wild-type littermates were largely diagnosed with arrested follicular development. The mammary ductal architecture in untreated 129B2+/- mice revealed a subtle inhibited branching phenotype that was enhanced with DES treatment. However, no significant differences were observed in ovarian pathology between 129B2+/+ and 129B2+/- mice. These data suggest that estrogenic compounds may modulate mammary gland or ovarian morphology in BALB/cB1+/- and 129B2+/- mice. These observations are consistent with the hypothesis that compromised DNA repair processes in cells harboring Brca1 or Brca2 mutations lead to inhibited growth and differentiation compared with the proliferative response of wild-type cells to DES treatment.

Polydrug-using adolescent mothers and their infants receiving early intervention.

This study investigated the effects of an intervention for polydrug-using adolescent mothers. The program included educational, vocational, and parenting classes; social and drug rehab; and day care for their infants while they attended school half-day. The drug-exposed infants were similar to the nonexposed infants on traditional birth measures, although they had inferior Brazelton Neonatal Behavioral Assessment Scale scores, including habituation, orientation, abnormal reflexes, general irritability, and regulatory capacity. The drug-exposed infants also spent less time in quiet sleep and more time crying and showing stress behaviors. Both the mothers and the infants in the drug groups demonstrated inferior interactions, and their dopamine and serotonin levels were significantly higher. As early as 3 months (following 3 months of intervention), the drug rehab mothers and their infants looked more like the nondrug group in their interactions; by 6 months, they looked similar on virtually every measure. At 12 months, the infants of drug rehab mothers (versus the drug control group) had superior Early Social Communication Scale scores and Bayley Mental scale scores, as well as significantly greater head circumference and fewer pediatric complications. The drug rehab mothers also improved on several lifestyle variables. They demonstrated a lower incidence of continued drug use and repeat pregnancy, and a greater number continued school, received a high school or general equivalency diploma, or were placed in a job. Thus, a relatively cost-effective high school based intervention had positive effects on both adolescent mothers who had used drugs and their infants.

PIP: The impact of an early childhood intervention program on polydrug-abusing US adolescent mothers and their infants was evaluated. The program, which was located in a vocational school attended by the mothers, included drug rehabilitation, social skills training, parenting classes, job training, and relaxation therapy. Outcomes in 126 drug-exposed mothers 16-21 years of age who participated in the program were compared to those recorded among non-drug-using adolescent mothers who participated in the program and drug-using control mothers who did not participate. All three groups were similar in terms of age, education, socioeconomic status, and ethnicity, but drug-abusing mothers had higher rates of depression and stress. At baseline, drug-exposed infants had lower scores on the measures of habituation, orientation, abnormal reflexes, general irritability, and regulatory capacity on the Neonatal Behavioral Assessment Scale. Drug-exposed infants spent less time sleeping and more time crying and showing stress behaviors. The drug groups also had lower Optimal Interaction Rating Scale scores for both mothers and infants. Their dopamine and serotonin levels were higher than those recorded among non-drug-using mothers and their cortisol levels were lower. However, after 6 months of participation in the intervention program, the drug-using mothers had Beck Depression Inventory scores and interaction ratings that approached those of non-drug-using mothers and exceeded those among drug-using controls. Similar trends were observed for infants' head circumference and scores on the Early Social Communication Scale and the Bayley Mental Status Scale. Moreover, drug-using adolescent mothers who participated in the program demonstrated a lower incidence of repeat pregnancy and continued drug use than those who were not enrolled in the program; moreover, they were more likely to receive their high school diploma and be placed in jobs. Interventions such as this have the potential to attenuate the developmental delays of infants of drug-exposed adolescents.

"Depressed" mothers' perceptions of infant vulnerability are related to later development.

Fifty-four depressed and non-depressed mothers were interviewed when their infants were 3 and 12 months of age. The depressed mothers assigned greater vulnerability scores and their infants engaged in less exploratory play and had lower Bayley mental and motor scores. The depressed mothers' vulnerability scores at 3 months were related to less exploratory play in their infants as well as lower Bayley mental scores at 12 months.