Ethylnitrosourea induces neoplasia in zebrafish (Danio rerio).

The zebrafish (Danio rerio) has been successfully used to discover hundreds of genes involved in development and organogenesis. To address the potential of zebrafish as a cancer model, it is important to determine the susceptibility of zebrafish to tumors. Germ line mutations are most commonly induced for zebrafish mutant screens by exposing adult male zebrafish to the alkylating agent, ethylnitrosourea (ENU). To determine whether ENU induces tumors, we compared the incidence of tumors in ENU-treated fish with untreated controls. Interestingly, 18 of 18 (100%) fish mutagenized with either 2.5 or 3.0 mM ENU developed epidermal papillomas, which numbered 1 to 22 per fish, within 1 year of treatment. The induced epidermal lesions included epidermal hyperplasia, flat papillomas (0.2 to 1.2 mm), and pedunculated papillomas (1.2 to 8 mm in greatest dimension), but no skin cancers. Angiogenesis was evident in papillomas larger than approximately 1 mm. All but two papillomas contained the three cell types (keratinocytes, club, and mucous cells) of normal zebrafish epidermis; histologic variants lacked either club cells or mucous cells. Two cavernous hemangiomas and a single malignant peripheral nerve sheath tumor were also found in the treated fish. None of five untreated controls developed tumors. These studies establish the feasibility of the zebrafish as an experimental model for the study of skin tumors.

Intrusive caregiving and quality of attachment in prenatally drug-exposed toddlers and their primary caregivers.

The relation between caregiver intrusiveness and the quality of attachment was tested among 51 prenatally drug-exposed toddlers and their primary caregivers. Biological mothers and kinship/foster caregivers neither differed as to caregiver intrusiveness nor as to their toddlers' attachment security and attachment organization. Insecure and disorganized/disoriented attachments were found to be more prevalent in this sample than in normal samples. In keeping with recent findings in non-drug-abusing samples (Isabella & Belsky, 1991; Lyons-Ruth, Repacholi, McLeod, & Silva, 1991), more caregivers of toddlers with avoidant or disorganized/disoriented attachments were found to be intrusive than caregivers of toddlers with secure or resistant attachments.

Intervening in severe physical child abuse cases: mental health, legal, and social services.

OBJECTIVE: To examine the child protection process in cases of severe physical abuse, to compare characteristics of the families with risk factors previously reported in the published literature, and to develop recommendations about the use of mental health professionals in such cases. METHOD: Reviewers examined 30 case records of severely physically abused children under age 5, nominated by child protection workers and mental health providers. The reviewers recorded demographic, clinical, and case process information such as mental health and other referrals, reunification status, and frequency of criminal prosecution. A case study was described. RESULTS: The parents displayed a range of psychological characteristics (e.g., depression, anxiety, personality disorders) and life problems (e.g., domestic violence, substance abuse, abused as child). The majority of parents denied the abuse. The children were very young (more than half under 6 months old) and many had difficult births or medical problems prior to the abuse. The most common services offered were individual psychotherapy and parenting classes. More than half of the children reunified with at least one parent within I year. Forty percent of the cases involved criminal prosecution. CONCLUSIONS: Reunification occurred more quickly and more often than expected based on the severity of the injuries. The system often relies on psychotherapy to correct the abusive behavior, even when the perpetrator remains unknown and specific risks such as substance abuse or domestic violence are present. The authors advise utilizing multidisciplinary teams for recommendations regarding reunification.

Maternal sensitivity during infancy and subsequent life events relate to attachment representation at early adulthood.

A prospective longitudinal research study of 86 prematurely born children from birth to age 18 years provided empirical evidence for continuity from infancy experience to representations of attachment at age 18 years. Young adults whose representation of attachment was dismissing had been objectively observed during infancy, 16-17 years earlier, to receive less sensitive maternal care than those infants who were later judged at early adulthood to have secure or preoccupied representations. Infancy experience alone did not differentiate young adults with secure representations from those with preoccupied representations. Rather, adverse life events through age 12, particularly parental divorce, reduced the likelihood of secure representations and increased the likelihood of preoccupied representations. The absence of adverse life events did not increase the likelihood of security for those who had not experienced early sensitive caregiving.

Maltoma of the thyroid in a man with Hashimoto's thyroiditis.

We report the case of a 42-yr-old man with primary thyroid lymphoma arising from mucosa-associated lymphoid tissue (MALT-lymphoma, maltoma). The patient underwent a hemithyroidectomy for a growing mass in the right lobe of the thyroid while being treated with 1-thyroxine for Hashimoto's thyroiditis. The clinical diagnosis of Hashimoto's disease was confirmed by aspiration biopsy of the mass during the course of L-thyroxine treatment. Postoperatively, histology showed atypical lymphoproliferative infiltrates suspicious of low-grade non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue-type, coexisting with a reactive process typical of chronic lymphocytic thyroiditis. Immunophenotyping showed a mixed B- and T-lymphocyte population, which was nondiagnostic. However, Southern blot analysis revealed a clonal rearrangement of the Ig heavy chain gene. This case demonstrates that cytology or histology may not distinguish between reactive or low-grade lymphomatous thyroid processes. The use of molecular technique was essential to prove clonality and the presence of lymphoma.

Psychopathology, mother-child interaction, and infant development: substance-abusing mothers and their offspring.

The course of severe depressive symptoms from pregnancy to 6 months postpartum, as well as the occurrence of severe paranoid symptoms prenatally, were examined by the Millon Clinical Multiaxial Inventory I and the Beck Depression Inventory, in 78 women who were heavy, chronic cocaine users and who retained custody of their children after birth. Six months postpartum, the quality of caregiving was observed and assessed in the home, and the children were assessed on the Bayley MDI Index in the laboratory. Mothers who were depressed and paranoid prenatally, regardless of whether the depression continued to 6 months postpartum, were less sensitive in caregiving than women without severe symptoms of paranoia or depression during pregnancy or those who reported only depression that lifted by 6 months postpartum. Mothers who were depressed prenatally and continued to be depressed by 6 months postpartum, regardless of the presence or absence of paranoia, had infants who earned lower Bayley MDI scores than the offspring of women without severe psychological symptoms or women whose depression had lifted. Severe depressive symptoms during pregnancy, if they did not continue to 6 months postpartum, did not appear to adversely influence either caregiving or infant functioning.

Maternal ego development and mother-infant interaction in drug-abusing women.

The purpose of this study was to expand our knowledge about factors in substance-abusing women, other than chronic drug abuse, that may influence maternal caregiving behaviors. Specifically, the study explored relationships between maternal characteristics and mother-infant interaction in a sample of drug-abusing women to determine whether drug-addicted mothers' level of ego development affected mother-infant interaction at 1 month. Data collection occurred during a prenatal lab visit and 1 month postpartum and included a clinical interview, self-report on participants' addiction severity, clinical personality inventory, ego development test, and videotaped observation of mother-infant feeding interactions. Only ego development, and to a lesser degree psychological symptoms associated with substance abuse, were found to be significant predictors of maternal-child interaction at 1 month. This points to the need to focus on building internal resources in providing substance abuse treatment and other services for substance-abusing mothers.

Issues in subject recruitment and retention with pregnant and parenting substance-abusing women.

To advance knowledge about the treatment of addiction among pregnant women and other women of childbearing age, investigators must adhere to the requirements of a strict experimental research design while concurrently providing clinical services. This means that researchers must address a variety of difficult questions, including the following: Was the sample large enough? Were the criteria for subject inclusion and exclusion well defined? Did the process of recruitment result in a sample that could be generalized to a larger population, or was the sample biased in some way? Was assignment to groups clearly random? What was the attrition rate? Was attrition the same in both experimental and comparison groups? Did baseline measures collect enough information to permit a description of the facts that were associated with attrition in each group? Was the attrition rate so high that the retained sample had special characteristics? If so, what were these features? This chapter highlights several problems related to these questions, describes the difficulties that investigators have faced in meeting clinical and research challenges to date, and suggests strategies for overcoming some obstacles. In establishing the Perinatal-20 project, the National Institute on Drug Abuse took an informed first step in organizing a substantial research effort to investigate treatment modalities that incorporate services specific to the needs of substance-abusing women who have children. This initial effort has resulted in a beginning knowledge base that can be used to refine and expand future treatment efforts. Even the issue of the "study unit" for this population is evolving. Today's researchers are attempting to determine whether the mother alone or the mother along with her dependent children constitutes the study unit. This question also has led professionals in the field to examine a range of specific outcome priorities, and investigators just now are beginning to determine exactly what needs to be evaluated in gauging the effectiveness of treatment. Is success measured on the basis of the woman's progress with abstinence alone, or does it also include her role with her children? Is it determined on the basis of her relationship with her children or the children's growth and development? Compared with providing services for and studying single adult subjects, developing treatment for women and their children presents researchers with a more complex task and requires expanded clinical services (Gallagher 1990, pp. 540-559). As in most fields of study, initial research data in substance abuse treatment for pregnant and parenting women are derived from samples of convenience, as described above. To put this information in perspective, future research will require a wider and more representative spectrum of the population. Furthermore, tensions between clinical needs and research requirements must be considered in advance, and methods for relaxing these tensions will be critical to the success of future efforts. For example, members of both the research and clinical staff teams must be absolutely clear about the study design and the requirements of reliable research. Where possible, potential ambiguities about group assignment, project services, subjects' responsibilities, and so forth must be incorporated into subject consent forms so that the subjects also are apprised of potential problems and their solutions. A final caution to future investigators is to be aware of the economic, physical, and personnel limitations of the range of treatment services that can be provided in a research demonstration study involving this population. Because of these limitations and the extensive range of services the subjects of the studies require, treatment components must be discrete and carefully defined to prevent programs from becoming impractically diverse and unclear. Research goals must be attainable and measurable.(ABSTRACT TRUNCATED)

Perineurioma.

Perineurioma is a rare, probably benign peripheral nerve sheath neoplasm. Perineurial cell origin is most efficiently demonstrated immunohistochemically by positivity for epithelial membrane antigen and negativity for S-100 protein and Leu 7.

Development of infants born to cocaine-abusing women: biologic/maternal influences.

This study investigated the influence of gestational age, birthweight, caregiving, and maternal personality characteristics on the development of 51 six-month-old infants born to and being reared by cocaine-abusing mothers. Two self-report measures were administered to the pregnant women at intake: the ASI (quantifying drug use) and the MCMI (describing DSM-III Axis II personality characteristics and Axis I clinical syndromes). Infants' biologic vulnerability was assessed by gestational age and birthweight. Caregiving was assessed 6 months later in the home, using the HOME Inventory and maternal caregiving behavior rating scales. Infant development was assessed in the laboratory at 6 months using the Bayley Scales of Infant Development. Higher Bayley scores were associated with heavier birthweight and increased maternal sensitivity. Furthermore, mothers of infants with shorter gestations were found to be more sensitive caregivers, whereas mothers who reported more histrionic-gregarious, narcissistic, borderline-cycloid, and/or paranoid personality characteristics during pregnancy were less sensitive caregivers. Surprisingly, mothers who reported more depressive symptoms during pregnancy provided more sensitive care.

Metastatic signet ring carcinoma of the breast as a source of positive cervicovaginal cytology. A case report.

The cellular manifestations of extrauterine cancer have been well documented. While finding metastatic carcinoma in gynecologic specimens should not be unexpected, descriptions of certain types of neoplasms are not well represented in the cytology literature. We describe the clinical, cytopathologic and histologic features of a case of signet ring cell breast carcinoma metastatic to the uterine cervix. Signet ring cell breast carcinoma is a rare neoplasm, and its possible histogenesis is discussed.

Glucose turnover in type I diabetic subjects during exercise. Effect of selective and nonselective beta-blockade and insulin withdrawal.

OBJECTIVE: To assess the effect of selective beta 1-blockade (atenolol and betaxolol) and nonselective beta-blockade (propranolol) on glucose turnover in subjects with insulin-dependent (type I) diabetes mellitus during moderate exercise. RESEARCH DESIGN AND METHODS: Five subjects with type I diabetes were infused with insulin and then exercised for 1 h, after pretreatment with each of the three drugs or saline and, on a separate day, after withdrawal of insulin. Glucose turnover was measured using tritiated glucose. RESULTS: Plasma glucose, initially 9.2 +/- 0.5 mmol/L (mean +/- SE) when insulin infused and 14.0 +/- 0.8 when insulin was withdrawn, fell on exercise by 3.4 +/- 1.1 mmol/L (P < 0.05) saline, 4.0 +/- 0.8 mmol/L (P < 0.01) with betaxolol, 3.8 +/- 0.7 mmol/L (P < 0.01) with atenolol, 5.0 +/- 0.6 mmol/L (P < 0.005) with propranolol, and 1.7 +/- 1.0 mmol/L (NS) when insulin was withdrawn. Propranolol, but not the other beta-blockers, caused a significantly greater fall in glucose on exercise than during the control study. Glucose appearance rate (Ra) was similar basally and rose to an almost identical level in all five groups during exercise. Glucose disappearance rate (Rd) rose similarly during exercise, except after propranolol when the rise was significantly greater than with saline (P < 0.01). Failure of glucose to change significantly during exercise when insulin had been withdrawn was associated with the smallest rise in Rd and the highest nonesterified fatty acid concentrations. Propranolol and betaxolol, but not atenolol, reduced nonesterified fatty acids. CONCLUSIONS: We conclude that the greater fall in glucose on exercise after beta-blocking drugs is probably largely a direct effect of beta 2-blockade on muscle, increasing the exercise-induced rise in Rd glucose. This offers support to the use of beta 1-specific drugs, where beta-blockade is necessary in type I diabetes.

Preterm children at early adolescence and continuity and discontinuity in maternal responsiveness from infancy.

Patterns in mother-child interaction from infancy to age 12 were investigated in a prospective, longitudinal study of 44 English-speaking mothers and their preterm children. Maternal responsiveness was assessed by home observations during infancy and the Family Interaction Q-Sort at age 12, derived from 2 structured laboratory situations requiring cooperation of mother and child. A cluster of maternal behaviors of critical control toward the toddler was assessed at age 2 years. Children of mothers who were consistently more responsive during both infancy and early adolescence, as well as children whose mothers became more responsive by age 12, achieved higher IQ and arithmetic scores, had more positive self-esteem, and their teachers reported fewer behavioral and emotional problems than children of mothers who were consistently less responsive both during infancy and at age 12. Continuity in parenting behaviors was related to control and criticism beginning in the toddler period and not to degree of responsiveness to the infant.

Mothers' use of personal pronouns when talking with toddlers.

The verbal interaction of 2-year-old children (N = 46; 16 girls, 30 boys) and their mothers was audiotaped, transcribed, and analyzed for the use of personal pronouns, the total number of utterances, the child's mean length of utterance, and the mother's responsiveness to her child's utterances. Mothers' use of the personal pronoun we was significantly related to their children's performance on the Stanford-Binet at age 5 and the Wechsler Intelligence Scale for Children at age 8. Mothers' use of we in social--vocal interchange, indicating a system for establishing a shared relationship with the child, was closely connected with their verbal responsiveness to their children. The total amount of maternal talking, the number of personal pronouns used by mothers, and their verbal responsiveness to their children were not related to mothers' social class or years of education.

Prenatal exposure to drugs: behavioral distortions reflecting CNS impairment?

In order to disentangle the effects on development of prenatal drug exposure from the effects of poor prenatal care, perinatal complications, and low socioeconomic status, toddlers prenatally exposed to drugs were compared to high risk preterm toddlers of similar ethnicity and social class. Intellectual functioning and quality of play were assessed. The drug exposed toddlers had significantly lower developmental scores and less representational play. Furthermore elements of their play were characterized by the investigators as a soft neurological sign. The question of possible CNS impairment is raised.