Serologic responses to peptides of Anaplasma phagocytophilum and Borrelia burgdorferi in dogs infested with wild-caught Ixodes scapularis.

Anaplasma phagocytophilum and Borrelia burgdorferi are both transmitted by Ixodes spp. and are associated with clinical illness in some infected dogs. This study evaluated canine antibody responses to the A. phagocytophilum p44 peptides APH-1 and APH-4 as well as the B. burgdorferi C6 peptide before and after doxycycline treatment. A total of eight dogs were infested with wild-caught I. scapularis for 1 week. Blood was collected prior to tick attachment and from Days 3-77 to 218-302 with doxycycline treatment beginning on Day 218. Blood was assayed for A. phagocytophilum DNA by PCR assay. Sera was assessed for antibodies by immunofluorescent antibody (IFA) test and ELISA. Anaplasma phagocytophilum DNA was amplified from blood of all dogs by Day 7. Antibodies to APH-4 were detected in serum as early as 14days after tick exposure and six dogs had APH-4 antibodies detected 3-7 days before antibodies against APH-1. All dogs were seropositive for A. phagocytophilum from Days 218 to 302. Antibodies to B. burgdorferi were detected in 6/8 dogs beginning 21days after I. scapularis infestation. Among the five dogs that remained seropositive at Day 218, C6 antibody levels declined on average 81% within 84days of initiating treatment. The results suggest that the APH-4 peptide may be more useful than APH-1 for detecting antibodies earlier in the course of an A. phagocytophilum infection. After doxycycline administration, C6 antibody levels but not APH-1 or APH-4 antibody levels decreased, suggesting a treatment effect on C6 antibody production.

Experimental Dirofilaria immitis infection in dogs: effects of doxycycline and Advantage Multi® administration on immature adult parasites.

To better understand the efficacy of doxycycline and 10% imidacloprid+2.5% moxidectin (Advantage Multi(®); Bayer Animal Health, Shawnee Mission, Kansas) on immature adult Dirofilaria immitis parasites and the results of antigen tests, 12 healthy, randomly selected dogs were experimentally infected with D. immitis and monitored for 407 days. Two dogs in each of three subgroups of four dogs were each infected with six (total of 6 dogs) or 12 (total of 6 dogs) D. immitis infective third-stage larvae (L3) obtained from infected mosquitoes. Doxycycline (10mg/kg per os twice daily×30 days) and 10% imidacloprid+2.5% moxidectin (1ml/kg by topical application every 30 days) treatment was initiated at 105 (Group A) and 149 (Group B) days post infection (PI) in two groups. One subgroup of two dogs given 6 L3 and one subgroup of two dogs given 12 L3 remained as untreated controls (GroupC). Serum obtained regularly throughout the study was evaluated by ELISA (PetChek(®) Heartworm-PF Antigen Test, IDEXX Laboratories, Inc.) for D. immitis adult circulating antigens. Six of the eight dogs in the treated groups had detectable antigenemia starting between 148 and 240 days post infection, but antigen was not detected in any treated dog at the end of the study. In the control subgroups, the dogs that received 6 L3 had no detectable antigen while the two dogs that received 12 L3 had detectable antigen beginning on Day 180 that persisted until the end of the study. None of the infected dogs had evidence of circulating microfilariae. At necropsy, no heartworms were recovered from the treated dogs, but all dogs in the untreated group had viable adult heartworms. These results indicate that early immature adult worms (3.5 and 5 months of age) of D. immitis were susceptible to a combined treatment regimen of doxycycline and 10% imidacloprid+2.5% moxidectin.

Do referrals work? Responses of childbearing newcomers to referrals for care.

BACKGROUND: Health care post-birth may include referrals for additional care. Migrant (i.e., refugee, asylum-seeker, and immigrant) women frequently do not follow-up referrals for care and could be at increased health risk as a consequence. We sought to explore the inhibitors and facilitators of migrant women for following through with referrals for care. METHODS: Twenty-five women living in Montreal who had received a referral completed semi-structured interviews. RESULTS: Inhibitors included language barriers, transportation problems, scheduling appointments, absence of husband, absence of childcare, cold weather, perceived inappropriate referrals, and cultural practice differences. Facilitators included choice of follow-up facilitator, appropriate services, empathetic professionals, and early receipt of information. DISCUSSION: Results indicate that migrant women may not be receiving the care they and their newborns need once a concern is identified. This suggests conceiving of a different approach to the care of this population post-birth, which could include partnering with social or religious networks.

Stability and change in depressive symptoms from pregnancy to two months postpartum in childbearing immigrant women.

The present study explored changes in mental health and functional status from pregnancy to 2 months postpartum in a sample of 106 childbearing immigrant women. Three sets of variables were examined in relation to postpartum depressive symptomatology: (1) prenatal depression, worries, and somatic symptoms; (2) social relationships (marital quality and social support), and (3) factors related to migration (premigration stress and length of stay in the host country). We found that 37.7% of the women in this community sample scored above the cutpoint of 12 on the Edinburgh Postnatal Depression Scale; prenatal depressive and somatic symptoms, as well as marital quality, were the best predictors of postpartum depressive symptomatology. An examination of differing trajectories from pregnancy to the postpartum period suggests that women with relatively few somatic complaints, low levels of perinatal stress, and satisfactory marital relations were less likely to exhibit mental health problems during pregnancy and postpartum. Women who were not depressed prenatally but reported postpartum depressive symptomatology exhibited several predisposing risk factors during pregnancy: many somatic complaints, high perinatal anxiety, and premigration stress. Women who were depressed during pregnancy but not postpartum reported improved physical function after childbirth. The implications of these findings for screening childbearing immigrant women are discussed.

Prevalence of Cryptosporidium spp. and Giardia spp. in five marine mammal species.

Cryptosporidium spp. and Giardia spp. are protozoan parasites that are often associated with severe diarrheal disease in a variety of mammals. Although these parasites have been extensively studied in terrestrial ecosystems, little is known about either parasite in the marine environment. Therefore, the objective of this study was to determine the prevalence of both Cryptosporidium spp. and Giardia spp. in 5 marine mammal species. Fecal samples were collected from 39 bowhead whales (Balaena mysticetus), 49 North Atlantic right whales (Eubalaena glacialis), 31 ringed seals (Phoca hispida), 22 bearded seals (Erignathus barbatus), and 18 beluga whales (Delphinapterus leucas) between 1998 and 2003. Using an immunofluorescent assay, parasites were detected in the feces of bowhead whales, right whales, and ringed seals, while neither parasite was detected in samples from bearded seals or beluga whales. Overall, prevalences were highest in ringed seals (Cryptosporidium spp., 22.6%; Giardia spp., 64.5%) and right whales (Cryptosporidium spp., 24.5%; Giardia spp., 71.4%) and lowest in bowhead whales (Cryptosporidium spp., 5.1%; Giardia spp., 33.3%). To our knowledge, this is the first report of Cryptosporidium spp. and Giardia spp. in either whale species and of Cryptosporidium spp. in the ringed seal.

Pregnant women's social status, stress, self-esteem, and their infants' sex ratio at birth.

A reported association of social status of parents with infants' sex ratio at birth and of psychological stress (score on Beck Depression Inventory) with sex ratio were not supported by our analysis, but the possibility of an association between scores on the Rosenberg Self-esteem scale and sex ratio at birth for a sample of 385 pregnant women showed that women who have given birth to boys scored lower on self-esteem during pregnancy than those who have given birth to girls. Some explanations are reviewed to discuss this unforeseen association.

In vitro and in vivo pharmacological characterizations of the antitumor properties of two new olivacine derivatives, S16020-2 and S30972-1.

S16020-2, a new olivacine derivative and a topoisomerase II inhibitor, has recently entered clinical trials. New analogues and derivatives have been synthesized from the S16020-2 compound. Preliminary data indicate that S30972-1, one of these S16020-2 derivatives, may exhibit a comparatively higher level of antitumor potency associated with an improved therapeutic index than does S16020-2. The antitumor activities of S16020-2 and S30972-1 were therefore characterized both in vitro and in vivo, with Adriamycin and etoposide chosen as reference compounds. The in vitro data show that S30972-1 is a topoisomerase II inhibitor, mediating its activity through an ATP-dependent mechanism such as S16020-2. The two olivacine derivatives exhibited similar activities in vitro at the levels of the global growth of six human cancer cell lines, of the induction of apoptosis, and of the G2 cell cycle phase arrest. The in vivo antitumor activity characterization included the use of two murine leukemia types (P388-LEU and L1210-LEU), two murine lymphoma-like models (P388-LYM and L1210-LYM), two mammary adenocarcinomas (MXT-HI and MXT-HS), and one melanoma (B16). The data show that S30972-1 is actually more efficient in vivo than S16020-2, a feature that may relate to the fact that S30972-1 is less toxic than S16020-2. The S30972-1 compound exhibited in vivo a level of antitumor activity that was also actually higher than that exhibited by Adriamycin and similar to that exhibited by etoposide.

Cellular resistance to the antitumor DNA topoisomerase II inhibitor S16020-2: importance of the N-[2(Dimethylamino)ethyl]carbamoyl side chain.

The new olivacine derivative S16020-2 (NSC-659687) is a DNA topoisomerase II inhibitor endowed with a remarkable antitumor activity against various experimental tumors. In vitro physicochemical properties of this compound, in particular its interaction with DNA and DNA topoisomerase II, were very similar to those of ellipticine derivatives, except for a strictly ATP-dependent mechanism of cleavable complex induction. From the Chinese hamster lung fibroblast cell line DC-3F, a subline resistant to S16020-2, named DC-3F/S16, was selected by adding stepwise increasing concentrations of the drug to the cell growth medium. Whereas DC-3F/9-OH-E cells, a DC-3F subline resistant to 9-hydroxy-ellipticine, are cross-resistant to S16020-2, DC-3F/S16 cells are only very weakly cross-resistant to ellipticine derivatives, indicating that, despite their structural similarity, these compounds may differ in their mechanisms of action. Uptake and efflux rates of S16020-2 were identical in the resistant and the sensitive cells. Topoisomerase IIalpha was expressed at the same level in both sensitive and resistant cells, whereas expression of the beta-enzyme was approximately 50% lower in the resistant cells. Sequencing of both alpha- and beta-isoform cDNAs revealed a point mutation that converts Arg(486) to a Gly in the alpha cDNA, whereas the beta cDNA was not modified. This amino acid substitution in a highly conserved sequence of the enzyme appears to be responsible for the resistance to S16020-2. Comparative analysis of the properties of the ellipticine and S16020-2-resistant cells suggests that S16020-2, which is a DNA intercalator, might also interact with this enzyme amino acid sequence through its side chain.

Minor physical anomalies and family adversity as risk factors for violent delinquency in adolescence.

OBJECTIVE: Minor physical anomalies are considered indicators of disruption in fetal development. They have been found to predict behavioral problems and psychiatric disorders. This study examined the extent to which minor physical anomalies, family adversity, and their interaction predict violent and nonviolent delinquency in adolescence. METHOD: Minor physical anomalies were assessed in a group of 170 adolescent boys from low socioeconomic status neighborhoods of Montréal. The boys had been enrolled in a longitudinal study since their kindergarten year, when an assessment of family adversity had been made on the basis of familial status and the parents' occupational prestige, age at the birth of the first child, and educational level. Adolescent delinquency was measured by using self-reported questionnaires and a search of official crime records. RESULTS: Results from logistic regression analyses indicated that both the total count of minor physical anomalies and the total count of minor physical anomalies of the mouth were significantly associated with an increased risk of violent delinquency in adolescence, beyond the effects of childhood physical aggression and family adversity. Similar findings were not found for nonviolent delinquency. CONCLUSIONS: Children with a higher count of minor physical anomalies, and especially a higher count of anomalies of the mouth, could be more difficult to socialize for different and additive reasons: they may have neurological deficits, and they may have feeding problems in the first months after birth. Longitudinal studies of infants with minor physical anomalies of the mouth are needed to understand the process by which they fail to learn to inhibit physical aggression.

[The ice storm: an opportunity to study the effects of prenatal stress on the baby and the mother.]. / La tempête de verglas : une occasion d'étudier les effets du stress prénatal chez l'enfant et la mère.

Over the last several years, studies have shown that stressful experiences during the pregnancy can predict levels of neurological development, as well as cognitive and psychological functioning, during childhood and adulthood. For example, Mednick (1997) has been studying the effects of a major earthquake in China on the psychological and intellectual development of the unborn child. Twenty-three years after the quake, significant differences have been found between the earthquake group and a control group born one year later in terms of intellectual functioning, depression, and the size of certain brain regions. Less severe events, such as a divorce or job loss during the pregnancy, may also increase the risk of obstetric complications and may have an effect on the baby's neurological well being, weight and head circumference at birth. Death of the baby's father during the pregnancy and natural disasters have both been associated with increased rates of depression, schizophrenia and criminality in adulthood. Several of these same effects have been found in studies of prenatal stress in non-human primates. Many of these studies suggest that the second trimester of pregnancy is a particularly critical period during which stressful events may compromise development of the fetus. Methodological constraints limit research on prenatal maternal stress. Animal studies are able to control for pre- and postnatal environments. However, animal studies have limited generalizability to humans for whom numerous risk and protective factors are in operation. Studies of human pregnancies cannot randomly assign subjects to stress conditions. Maternal personality and temperament may be associated with characteristics of a woman's child not only through genetic transmission of personality, but possibly also through differential exposure to difficult life conditions which may, in part, be self-imposed. In addition, studies of prenatal life events in humans have severely restricted variance; very large samples of women must be screened to identify even small numbers of women who have experienced major life events during the pregnancy. Finally, follow-back studies which show an association between prenatal events and later rates of mental illness, do not include timely evaluations of actual rates of exposure to the event, nor the pregnant woman's subjective or biological reactions to the event. In this paper, we present a review of the literature on prenatal maternal stress followed by a discussion of how the January 1998 Québec ice storm could be used to study the mechanisms by which prenatal stress may influence mental health outcomes in the unborn child.

Transfection of 9-hydroxyellipticine-resistant Chinese hamster fibroblasts with human topoisomerase IIalpha cDNA: selective restoration of the sensitivity to DNA religation inhibitors.

In the Chinese hamster lung cell line DC-3F/9-OH-E, selected for resistance to 9-OH-ellipticine and cross-resistant to other topoisomerase II inhibitors, the amount of topoisomerase IIalpha is 4-5-fold lower than in the parental DC-3F cells, whereas topoisomerase IIbeta is undetectable. Cloning and sequencing of topoisomerase IIalpha cDNAs from DC-3F and DC-3F/9-OH-E cells revealed an allele polymorphism, one allele differing from the other by the presence of seven silent mutations and three mutations in the noncoding region. In addition, the mutated allele contains three missense mutations located close to the ATP binding site (Thr371Ser) or to the catalytic site (Ala751Gly; Ile863Thr). To analyze the contribution of these topoisomerase IIalpha alterations to their resistance phenotype, DC-3F/9-OH-E cells were transfected with an eukaryotic expression vector containing the human topoisomerase IIalpha cDNA. In one transfected clone, the amount of topoisomerase IIalpha isoform and the catalytic activity were similar to that in the parental DC-3F cells. These cells, which contain only topoisomerase IIalpha, are then a unique mammalian cell line to analyze the physiological and pharmacological properties of this enzyme. However, the restoration of a nearly normal topoisomerase IIalpha activity in the DC-3F/9-OH-E cells did not have the same effect on their sensitivity to different enzyme inhibitors; a 75% reversion of the resistance, associated with a 2-3-fold increased stabilization of the cleavable complex, was observed with both etoposide and m-AMSA, two drugs that inhibit the DNA religation step in the enzyme catalytic cycle; in contrast, the transfected cells remained fully resistant to ellipticine derivatives that did not induce the stabilization of the cleavable complex. We hypothesized that a trans-acting factor, inhibiting the induction of cleavable complex formation by drugs that are not religation inhibitors, might be present in the resistant cells. However, such a factor was not detected in in vitro experiments, and other hypotheses are discussed.

Adaptation of parents in relation to their 6-month-old infant's type of disability.

The adaptation of parents to a disabled infant was studied in relation to the type of disability presented by the baby. Participants were divided according to three types of disability and one control group: patents of infants with (1) Down's syndrome (DS), (2) congenital heart disease (CHD), (3) a cleft lip and/or palate (CLP), and (4) no disability (ND). The data were collected using a self-administered questionnaire given to each parent 6 months after the birth of their baby. The measures included parenting stress, stress appraisal, and psychological distress. Overall, the results indicate that parents of infants with DS and parents of infants with CHD report greater levels of parenting stress and psychological distress than parents of babies with CLP or non-disabled infants. Mothers were found to report greater levels of stress and distress overall, but differences across diagnostic groups were similar for mothers and fathers. The implications of the findings for theory and clinical intervention are discussed.

ECG conduction delays associated with massive bupropion overdose.

BACKGROUND: Bupropion, a relatively new antidepressant, is highly regarded for its safety profile in therapeutic doses and in the overdose. Seizure is the primary adverse reaction associated with bupropion overdoses. Clinically significant cardiovascular complications are rare. CASE REPORT: We report the case of an adult male who ingested 9 g bupropion and developed neurologic toxicity as well as intraventricular conduction disturbances on electrocardiogram. Cardiac monitoring of these patients should be considered.

Birth order and fratricidal behaviour in Canada.

In 1996, Sulloway suggested that older siblings would be more fratricidal than younger ones. In Canada from 1974 to 1955, data on fratricide and sororicide do not support this hypothesis.

Paternal alcoholism, paternal absence and the development of problem behaviors in boys from age six to twelve years.

OBJECTIVE: The purpose of this study was to examine the association between paternal alcoholism, paternal absence, and the development and stability of behavioral problems in boys, from kindergarten to the end of elementary school. METHOD: A sample of 642 boys originating from low socioeconomic status (SES) families was used. Paternal alcoholism was established using the Short Michigan Alcohol Screening Test. Behavioral problems (opposition, hyperactivity, inattention, physical aggression and anxiety) were assessed by teachers' reports when the boys were 6 and 12 years old. Four groups of boys were created on the basis of paternal alcoholism (nonalcoholic, alcoholic) and family structure (intact families, nonintact/father-absent families). RESULTS: Consistent with personality theories of alcoholism, results showed that a propensity for physical aggression and low anxiety best distinguished sons of male alcoholics (SOMAs) from non-SOMAs at both ages (6 and 12 years), even when SES was controlled. In addition, SOMAs were more oppositional and hyperactive than non-SOMAs at both ages. No significant effects were observed for family structure or age, or an interaction between these factors and paternal alcoholism in the multivariate analysis. CONCLUSIONS: The results suggest that problem behaviors in SOMAs begin early and persist over time, and that paternal alcoholism and family structure are not associated with changes in boys' behaviors between kindergarten and the end of elementary school in this population, at least in the sample used.

Preference for sex of first child among women classified as androgynous and nonandrogynous.

This paper examined the relation between gender-role orientation and the preference for sex of firstborn child in 212 pregnant nulliparous women. The Bem Sex-role Inventory was used to assess gender-role orientation of participants. Analysis suggested that gender-role orientation, as measured does not effectively predict the preference for sex of firstborn child.

S16020-2, a new highly cytotoxic antitumor olivacine derivative: DNA interaction and DNA topoisomerase II inhibition.

S16020-2 (NSC-659687) is a new olivacine derivative that is highly cytotoxic in vitro and displays remarkable antitumor activity against various experimental tumors, especially some solid tumor models. Its antitumor activity is notably higher than that of 2-methyl-9-hydroxy-ellipticinium (NMHE) and comparable to that of doxorubicin HCl, although with a different tumor specificity. S16020-2 is being tested in phase I clinical trials. A study of the interaction of S16020-2 with DNA showed that it binds through intercalation between adjacent DNA base pairs, inducing an unwinding of 10 degrees of the double helix. Its DNA affinity is approximately equal to that of NMHE and decreases as a function of the salt concentration, indicating a significant electrostatic contribution to the overall binding free energy. S16020-2 did not interfere with the catalytic cycle of DNA topoisomerase I but stimulated DNA topoisomerase II-mediated DNA cleavage via a strictly ATP-dependent mechanism. The interactions of S16020-2 and NMHE with DNA topoisomerase II in vitro are very similar. Both drugs have the same DNA sequence specificity of cleavage and the same biphasic dose-effect response, and neither drug inhibited the rate of DNA religation. In contrast with these observations, in in vivo experiments, S16020-2 was able to induce topoisomerase II-mediated DNA strand breaks at concentrations 500-fold lower than NMHE. We conclude that DNA topoisomerase II most likely is the cellular target involved in the mechanism of cytotoxicity of S16020-2. Its higher biological activity and potency to induce cellular DNA cleavage suggest the involvement of as-yet-unidentified cellular factors.

Psychosocial predictors of depressive symptomatology level in postpartum women.

This study explored a multifactorial model for the prediction of the intensity of depressive symptoms in postpartum women. Data were gathered from 213 pregnant women during the second trimester of pregnancy and at 6 months postpartum. Participants were assessed according to a number of psychosocial variables. A path analysis indicated that four variables had a direct effect on postpartum depressive symptomatology level: lower occupational status, prenatal depression level, more distal stressors and a personal psychiatric history. Eight variables, which reflected past and present experiences, showed an indirect effect. The implications of these findings are discussed.

Perceptual defense and vigilance to perinatal stimuli.

The presentation times (milliseconds on a computer screen followed by a masking grid) required for the correct identification of tachistoscopically presented perinatal stimuli were compared for 30 pregnant women and 25 perimenopausal women. Analysis indicated a differential facilitation or inhibition of perception in logical relation to subjects' closeness to pregnancy or menopause: pregnant women are quicker to identify stimuli related to pregnancy or babies but slower to recognize pictures of a pregnant woman with her father or mother. This supports the validity of measurements based on the theory of perceptual defense or vigilance.