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.

Early synapsids neurosensory diversity revealed by CT and synchrotron scanning.

Non-mammaliaform synapsids (NMS) represent the closest relatives of today's mammals among the early amniotes. Exploring their brain and nervous system is key to understanding how mammals evolved. Here, using CT and Synchrotron scanning, we document for the first time three extreme cases of neurosensory and behavioral adaptations that probe into the wide range of unexpected NMS paleoneurological diversity. First, we describe adaptations to low-frequency hearing and low-light conditions in the non-mammalian cynodont Cistecynodon parvus, supporting adaptations to an obligatory fossorial lifestyle. Second, we describe the uniquely complex and three-dimensional maxillary canal morphology of the biarmosuchian Pachydectes elsi, which suggests that it may have used its cranial bosses for display or low-energy combat. Finally, we introduce a paleopathology found in the skull of Moschognathus whaitsi. Since the specimen was not fully grown, this condition suggests the possibility that this species might have engaged in playful fighting as juveniles-a behavior that is both social and structured. Additionally, this paper discusses other evidence that could indicate that tapinocephalid dinocephalians were social animals, living and interacting closely with one another. Altogether, these examples evidence the wide range of diversity of neurological structures and complex behavior in NMS.

Neuroprotective effects of novel phosphatidylglycerol-based phospholipids in the 6-hydroxydopamine model of Parkinson's disease.

Administration of VP025 (Vasogen Inc.), a novel drug formulation based on phospholipid nanoparticles incorporating phosphatidylglycerol, has previously been shown to have a neuroprotective effect in the brain. We examined the effect of VP025 in a rat model of Parkinson's disease, the 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle. VP025 or phosphate-buffered saline (PBS) was administered to rats 14 days, 13 days and 1 day before the unilateral 6-OHDA lesion. Functional integrity of nigrostriatal dopaminergic neurons was assessed 7 and 21 days later by amphetamine-induced rotational testing and we observed that rotational counts were significantly less in rats that were pretreated with VP025 compared with PBS-pretreated 6-OHDA-lesioned rats. Neurochemical analysis at 10 and 28 days after lesion revealed that VP025 protected against a 6-OHDA-induced decrease in concentrations of striatal dopamine and its metabolites. Immunocytochemical studies of the ipsilateral substantia nigra showed that VP025 significantly inhibited 6-OHDA-induced loss of dopaminergic neurons. We also observed that increases in immunostaining for activated microglia and for activated p38 in dopaminergic neurons of 6-OHDA-lesioned rats were prevented by VP025. This study shows that VP025 has significant protective effects on the 6-OHDA-lesioned nigrostriatal pathway and may therefore have potential for the treatment of Parkinson's disease.

Assigning exposure to pesticides and solvents from self-reports collected by a computer assisted personal interview and expert assessment of job codes: the UK Adult Brain Tumour Study.

OBJECTIVES: To compare assignment of occupational pesticide and solvent exposure using self-reported data collected by a computer assisted personal interview (CAPI) with exposure based on expert assessment of job codes. To discuss the advantages and disadvantages of using a CAPI to collect individual occupational exposure data. METHODS: Between 2001 and 2004, 1495 participants were interviewed using a CAPI for a case-control study of adult brain tumours and acoustic neuromas. Two types of occupational data were collected: (1) a full history, including job title from which a job code was assigned from the Standard Occupational Classification; and (2) specific details on pesticide and solvent exposure reported by participants. Study members' experiences of using the CAPI were recorded and advantages and disadvantages summarised. RESULTS: Of 7192 jobs recorded, the prevalence of self-reported exposure was 1.3% for pesticides and 11.5% for solvents. Comparing this with exposure expertly assessed from job titles showed 53.6% and 45.8% concordance for pesticides and solvents respectively. Advantages of the CAPI include no data entry stage, automatic input validation, and a reduction in interviewer bias. Disadvantages include an adverse effect on study implementation as a consequence of resources required for programming and difficulties encountered with data management prior to analysis. CONCLUSIONS: Different methods of exposure assessment derive different exposure levels for pesticide and solvent exposure at work. Agreement between self-reported and expert assessment of exposure was greater for pesticides compared to solvents. The advantages of using a CAPI for the collection of complex data outweigh the disadvantages for interviewers and data quality but using such a method requires extra resources at the study outset.

Significance of molecular marker-positive cells after autologous peripheral-blood stem-cell transplantation for non-Hodgkin's lymphoma.

PURPOSE: To evaluate the significance of molecular marker-positive cells in a cohort of non-Hodgkin's lymphoma (NHL) patients undergoing high-dose chemotherapy and autologous peripheral-blood stem-cell transplantation (PBSCT). PATIENTS AND METHODS: Twenty-eight PBSC transplants have been performed in 24 patients with poor-prognosis NHL. Molecular analysis of the t(14;18) (q32;q21) translocation (bcl-2/immunoglobulin [Ig] heavy-chain joining locus [JH] fusion) or antigen receptor gene rearrangements was performed to determine the presence of lymphoma cells at presentation, in PBSC harvests, and before and after autologous PBSCT. Kaplan-Meier estimates of survival and Cox regression analyses were used to test the effect of bone marrow involvement, tumor-cell contamination of PBSCs, disease stage, and chemotherapy sensitivity at transplantation, and presence of marker-positive cells post-PBSCT on disease-free and overall survival. RESULTS: Thirteen of 24 patients (54%) are alive following PBSCT at a median follow-up time of 654 days (range, 193 to 1,908). Nine patients are in complete remission (CR) at day 216 to 1,799 (median, 805) and four are alive following relapse (day 440, 573, 1,188, and 1,908). Eleven patients (46%) have died: three of transplant-related complications at day 0, 1, and 13, and eight of recurrent disease (day 132 to 1,330; median, 451). Longitudinal marker studies post-PBSCT showed that of 16 relapse events, 13 (81%) were positive for the lymphoma marker at or before clinically documented relapse. Marker studies became negative post-PBSCT in nine of nine patients who entered and remained in CR. Disease-free survival (DFS) was significantly shortened in patients in whom marker-positive cells were detected in serial samples posttransplantation (P = .006). Cox regression analysis showed that patients in this group had a 24 times higher risk of relapse (P = .03). CONCLUSION: The results show that the reappearance or persistence of marker-positive cells after autologous PBSCT is strongly associated with relapse.

Telepsychology for Posttraumatic Stress Disorder: A systematic review.

The effectiveness of psychological services provided remotely, telepsychology, for the management of Posttraumatic Stress Disorder (PTSD) was evaluated. Eleven studies (n = 472 participants) were identified from electronic database searches. Study quality was assessed, with studies characterised by small and underpowered samples. Effect sizes and associated confidence intervals (CIs) were calculated to determine the direction and magnitude of treatment change. Short-term treatment gains were reported for internet and video-based interventions. This included significant medium to large improvements (d range = 0.66-3.22) in cognitive and behavioural symptoms of depression, generalised anxiety and posttraumatic stress. However, the equivalence of telepsychology and face-to-face psychotherapy could not be determined, with few comparative studies available. Both treatment gains and deterioration were noted 1 to 6 months following treatment cessation, although this was based on limited follow-up data. Further larger scale and longitudinal research will help to ascertain the minimum requirements for the management and treatment of PTSD in a technology-supported environment.

A two-site immunoradiometric assay for human pregnancy-associated plasma protein A (PAPP-A) using monoclonal antibodies.

A rapid, sensitive immunoradiometric assay has been developed for human pregnancy-associated plasma protein A (PAPP-A) using a purified mouse monoclonal antibody as the tracer and a rabbit polyclonal antibody to this protein in the solid-phase antibody preparation. The assay showed no measurable cross-reaction (less than 0.1%) against a range of purified human placental proteins, and a good correlation with a previously described radioimmunoassay procedure when tested on samples taken throughout normal human pregnancies. No PAPP-A-like immunological activity could be detected in sera from non-pregnant women, confirming the absence of this protein from the circulation outside pregnancy.

beta-thromboglobulin and deep vein thrombosis.

The measurement of plasma beta-thromboglobulin as a potential diagnostic test for venous thrombosis has been investigated in 16 normal volunteers, 24 patients presenting with deep vein thrombosis (DVT) or pulmonary embolism and 46 patients screened by 125I fibrinogen test (IFT) for post-operative DVT. The normal mean was 33 ng/ml (range 15-117 ng/ml). Of the 24 patients with clinical thrombotic disease 22 presented with DVT confirmed by phlebogram or IFT and 2 presented with embolism confirmed by lung scan. At the time of first presentation 12 out of 24 had betaTG values greater than 70 ng/ml. All except 3 of this group of 24 patients had values of greater than 70 ng/ml at some stage during a subsequent week of daily sampling. DVT was detected in 13 out of 46 screened post-operative patients. There was a rise om betaTG observed within 24 hr of the IFT becoming positive but the mean rise did not reach significance at the 5% level. An association between DVT and high betaTG values has been confirmed. However, its clinical value cannot yet be fully elucidated until factors, probably related to blood sampling and clearance, are further investigated.

Concentration of oestrogens and androgens in human ovarian venous plasma and follicular fluid throughout the menstrual cycle.

The concentrations of androstenedione, testosterone, oestrone and oestradiol-17beta were measured in peripheral and ovarian venous blood and follicular fluid of women at various stages of the menstrual cycle. The concentration of oestradiol was similar in small follicles (diameter less than 8 mm) at all stages of the menstrual cycle and in large follicles (diameter greater than or equal to 8 mm) except during the mid- and late follicular phase when the concentration reached a peak (approximately 1500 ng/ml). The concentration of androstenedione was lowest in large preovulatory follicles at midcycle at a time when the secretion into the ovarian vein was markedly increased. The concentration of testosterone in large follicles (greater than or equal to 8 mm) was unchanged during the follicular phase whereas in small follicles there was a peak at mid-cycle. The rise in the concentration of testosterone and androstenedione at mid-cycle in peripheral plasma may be due to increased secretion by the preovulatory follicle into the ovarian vein. It is suggested that the relatively low concentration of androstenedione in follicular fluid of the preovulatory follicle arises from increased aromatization by granulosa cells in the course of oestrogen synthesis.

The relationship of placental protein 14 (PP14) in the mother and fetus to specific products of the human placenta.

Levels of placental protein 14 (PP14), human placental lactogen (hPL) and unconjugated oestriol (E3) were measured in maternal peripheral and umbilical arterial and venous blood obtained from 65 normal pregnancies at term delivery. PP14 levels were one order of magnitude higher in the mother than in the fetus. Neither maternal nor fetal levels of PP14 were related to the birthweight of the fetus. There was a relationship between maternal and umbilical venous levels of PP14, which suggests that fetal PP14 is derived by transfer from the mother, or that there is an independent fetal source with a control mechanism similar to that of the mother. The findings are compatible with earlier observations to the effect that PP14, in contrast to products such as hPL and E3, is not specific to the trophoblast.

The effect of horse placental tissue extracts and equine chorionic gonadotrophin on the proliferation of horse lymphocytes stimulated in vitro.

Commercial preparations of equine chorionic gonadotrophin (eCG) and extracts of horse placenta taken at 80 days gestation were incorporated into mixed lymphocyte culture and mitogen stimulation assays of horse peripheral blood mononuclear cells. A dose-related inhibition of lymphocyte proliferation, indicative of immunosuppressive activity, was observed in both systems, both with commercial eCG preparations and tissue extracts. Negligible inhibitory activity was observed with an extract of term placenta. The inhibitory activity of the placental samples was not related to their eCG content as measured by immunoassay. The fact that one pregnant horn allantochorion extract containing 50 IU/ml of eCG showed an identical dose-dependent lymphoproliferation-inhibitory activity to an extract of a second such allantochorion containing only 1.7 IU/ml of eCG suggests that this hormone does not inhibit lymphocyte proliferation and that commercially available eCG contains inhibitory contaminants.

Factors affecting blood stem cell collections following high-dose cyclophosphamide mobilization in lymphoma, myeloma and solid tumors.

Sixty patients with malignancy were enrolled in a study of high-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT). Stem cells were harvested prior to PBSCT using high-dose cyclophosphamide (CY) mobilization (4 or 7 g/m2) with collection of a median of 4.6 x 10(8)/kg mononuclear cells (range 0.2-9.5) and 21.6 x 10(4)/kg colony forming unit-granulocyte/macrophage (CFU-GM) (range 0.1-220). Forty-seven patients were mobilized once, 11 required two cycles and two required three cycles. Eight patients (13%) failed to reach the optimum CFU-GM target (greater than 15 x 10(4)/kg) following CY mobilization. A number of factors identified those patients who were likely to achieve optimum CFU-GM collections with CY mobilization. These included the use of the higher CY mobilization dose, a longer interval from last chemotherapy cycle to mobilization, and a higher premobilization bone marrow CFU-GM level. Patient's age, the degree of bone marrow infiltration, the nature of disease or the number of pre-mobilization chemotherapeutic cycles did not affect the ability to collect optimum CFU-GM numbers. Whilst the mobilization procedure was associated with moderate non-hematologic toxicity, significant hematological morbidity was observed primarily in patients mobilized using the 7 g/m2 dose. Refinements to the protocol, in particular the use of hematopoietic growth factors, are currently under investigation.

Suppression of in vitro lymphocyte reactivity to phytohemagglutinin by placental protein 14.

Crude human decidual extracts containing up to 26.6 mg/l of placental protein 14 (PP14) and purified PP14 were assessed for their effects on the in vitro lymphocyte reactivity to phytohemagglutinin (PHA). Both decidual extract and purified PP14 suppressed the mitogenic response to PHA with the suppression being dose-dependent over the range of PP14 concentrations investigated (0-26.6 mg/l). On the specific reduction of the PP14 content by a monoclonal anti-PP14 immunoadsorbant the suppression was reduced. The suppressive activity of PP14 was related to the degree of proliferation of the stimulated lymphocytes. These results suggest that PP14, which is present at peak levels in the first trimester of pregnancy and constitutes up to 10% of the soluble protein content of decidual tissue, may be an immunomodulator important for the survival of the implanting embryo and maintenance of early pregnancy.

A controlled study of psychoanalytic treatment of brittle diabetes.

The study compared two equivalent groups of 11 diabetic children with grossly abnormal blood glucose profiles necessitating repeated admissions to a hospital. Patients in the treatment group were offered an intensive inpatient treatment program including psychoanalytic psychotherapy three to four times a week, which took place on the hospital ward and lasted an average of 15 weeks. The intervention was highly effective in improving the diabetic control of the children, and this was maintained at a 1 year follow-up. Patients in the comparison group, who were offered only inpatient medical intervention, returned to their prehospitalization level of metabolic control within a period of 3 months from discharge.

Placental protein 14 levels in uterine flushing and plasma of women with unexplained infertility.

OBJECTIVES: To measure concentrations of placental protein 14 (PP14) in uterine flushings and plasma samples obtained from patients with unexplained infertility and to compare the results of those of normal fertile women. DESIGN: Prospective study. SETTING: Infertility and gynaecology outpatient clinics at the Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Sixteen patients with unexplained infertility and 12 normal fertile women who had been previously sterilized. INTERVENTIONS: Daily monitoring of luteinizing hormone (LH) to detect the LH surge; uterine flushings and blood samples were obtained on days 7, 10, and 12 after the LH surge. MAIN OUTCOME MEASURES: The measurement of PP14 concentration in uterine flushings and plasma samples throughout the luteal phase. RESULTS: Levels of PP14 in uterine flushings of patients with unexplained infertility were significantly lower than those of normal fertile women on days LH +10 and LH +12. No significant differences were observed between the two groups in PP14 levels in uterine flushings on day LH +7 and plasma samples on days LH +7, LH +10, and LH +12. CONCLUSIONS: Patients with unexplained infertility have reduced concentrations of PP14 in uterine flushings but not in plasma samples as compared with normal fertile women. Placental protein 14 measurement in uterine flushings may be a more valuable method of assessing endometrial function in infertile patients than plasma levels of the protein.

The effects of clomiphene citrate and cyclofenil on cervical mucus volume and receptivity over the periovulatory period.

OBJECTIVE: To determine the effects of clomiphene citrate (CC) and cyclofenil on cervical mucus (CM) volume and receptivity sampled serially over the periovulatory period. DESIGN: Using prospective luteinizing hormone (LH) timing CM volume and receptivity were compared in standard CC and cyclofenil-stimulated cycles using normal ovulatory cycles as controls. LOCATION: The Donor Insemination Unit at the University Research Clinic, Sheffield, United Kingdom. PATIENTS: Twenty anovulatory patients and 10 normally ovulating patients, all of whom were participating in a treatment cycle of donor insemination. INTERVENTIONS: The 20 anovulatory patients were allocated at random into two groups: group 1 was administered 50 mg of CC on days 2 to 6 of the menstrual cycle; group 2 was administered 400 mg of cyclofenil on days 3 to 12 of the menstrual cycle. All the patients were given a single treatment of donor insemination 24 to 36 hours after the onset of the LH surge. RESULTS: Clomiphene citrate and cyclofenil were shown to exert differential impacts on CM quantity and quality. In terms of quantity, the CC patients produced significantly lower volumes of CM than the cyclofenil patients and controls. In terms of quality, the CC patients and controls produced CM of similar receptivity, whereas the cyclofenil patients produced CM that was significantly more receptive to sperm than both the CC patients and controls. CONCLUSIONS: Neither CC nor cyclofenil exerted a detrimental impact on CM quality throughout the periovulatory period.

An analysis of the variation of plasma concentrations of placental protein 14 in artificial cycles.

OBJECTIVE: To analyze the factors affecting the variation of plasma concentration of placental protein 14 (PP14) in artificial cycles. DESIGN: The effects of different hormone replacement therapy (HRT) regimens were examined in a crossover design. SETTING: Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Eighteen women with premature ovarian failure: 6 associated with Turner's syndrome and 12 with idiopathic premature ovarian failure. INTERVENTIONS: Four different HRT regimens; 36 study cycles. MAIN OUTCOME MEASURES: Plasma PP14 concentrations on days 1, 15, 19, and 29 of the artificial cycles. RESULTS: In cycles treated with a standard HRT, the levels were similar to those of the natural cycle. Subjects with Turner's syndrome did not have elevated PP14 levels, whereas the majority (9/12 [75%]) of those with idiopathic premature ovarian failure had elevated levels on day 29 of the cycle. Levels of PP14 were reduced when either the doses of estradiol valerate were reduced to 1/3 or the doses of progesterone (P) were reduced to 1/5 of the standard HRT. CONCLUSIONS: Plasma levels of PP14 are dependent not only on P stimulation but also on adequate estrogen priming.

Round cells and sperm fertilizing capacity: the presence of immature germ cells but not seminal leukocytes are associated with reduced success of in vitro fertilization.

Fifty semen samples produced for IVF by patients diagnosed as having unexplained infertility were screened for leukocytes, leukocyte subsets, and immature germ cells using a mAB-based staining procedure. Nonfertilizing ejaculates were found to contain significantly larger numbers of immature germ cells, although no significant differences in leukocyte content were observed between groups. Neither sperm density or progressive motility were significantly different between fertilizing and nonfertilizing groups. We conclude that seminal leukocytes have little if any influence on the fertilizing capacity of the spermatozoa in patients undergoing IVF for unexplained infertility, but the presence of large numbers of germinal elements is associated with reduced fertilizing capacity and may be indicative of an immature sperm population.

Salivary beta-thromboglobulin: a possible marker for deep vein thrombosis following elective hip surgery.

The concentration of the platelet specific protein B-thromboglobulin, (BTG) was measured in salivary samples obtained pre and postoperatively from 30 patients without evidence of renal disease and having total hip replacement arthroplasty. When postoperative deep-vein thrombosis (DVT) was detected using percutaneous ascending phlebography there was total correlation with elevated salivary BTG levels taking 0.33 micrograms/1 or greater on 2 consecutive occasions or more as indicating a deep venous thrombus. Eight of nine patients with a positive diagnosis of DVT on urokinase scanning would have been diagnosed using the same criterion. However BTG was elevated in a further 5 patients in whom labelled urokinase failed to demonstrate a DVT. These may have been localised in the calf and thus missed by, or lysed prior to, the scanning technique.

Formation of a vitamin B-12-serum complex on heating at alkaline pH.

The binding of vitamin B-12 to serum proteins during heating at alkaline pH was investigated by gel filtration of serum supplemented with cyano[57Co]-cobalamin. Heating for 5 min at 100 degrees C destroyed most of the vitamin B-12 binding activity of serum but, with further heating, the vitamin B-12 became incorporated into a complex that did not correspond in molecular size to the original vitamin B-12 binding proteins. Radioassay of vitamin B-12 in heated serum showed correspondingly first an increase then a progressive decrease in the apparent vitamin B-12 level suggesting that, on heating, vitamin B-12 was initially released then subsequently complexed by the serum. The formation of complexed vitamin B-12 was abolished by the presence of the reducing agent dithiothreitol during the heating step.