Is adequate parenting compatible with maternal drug use? A 5-year follow-up.

INTRODUCTION: This prospective, cohort study compares child protection outcomes over the first 5 years of life in a group of children born to self-declared drug-using mothers recruited during pregnancy (cases) and a group of children matched for gestational age, chronological age, maternal neighbourhood and place of delivery whose mothers made no such declaration of problematic drug use (controls). METHODOLOGY: We monitored local child protection registers to identify cohort members who came to the attention of the local authority. RESULTS: Of the 71 original cases and 142 original controls, 55 (77%) and 96 (68%) remained in the area enrolled in local schools at 5 years of age. In total, 26 (47.3%) of the case children were subject to child protection procedures compared with 18 (18.8%) of the control children. This risk difference of 28.5% (95% CI 13.2% to 43.9%) has increased marginally since our previous report in this journal of child protection outcomes at 18 months of age (32% vs. 7%). However, the level of intervention deemed necessary to protect the child has increased significantly with six cases (compared with one control child) taken into the care of the local authority. CONCLUSIONS: Despite early maternal intentions and multiple supportive interventions, 27% of children born to women with significant substance abuse problems in our area required child protection during the pre-school years. Child protection risk assessment procedures need to weigh problematic maternal drug use heavily. Intervention studies with child welfare outcomes are needed to identify the most effective harm reduction strategies and inform public debate on how we can minimize child abuse related to substance misuse.

Rat synapsin 1 promoter mediated transgene expression in testicular cell types.

Previous reports described the rat synapsin 1 promoter as primarily neuron selective. However, ectopic expression of a transgene under the rat synapsin 1 promoter was also detected in testis from some transgenic mouse lines. Here we investigate which cells within the testis express a transgene consisting of the rat synapsin 1 promoter fused with luciferase. Synapsin 1-luciferase expression vectors were introduced into HeLa cells, into TM3 cells derived from mouse testicular Leydig cells, and into one-cell embryos to make transgenic mice. Indirect immunofluorescence suggests that nontransfected TM3 cells do not express endogenous synapsin 1. TM3 stable transfectants, however, expressed luciferase under the direction of the synapsin 1 promoter, in both promoter orientations. HeLa cells displayed only low levels of activity. Transgenic mice carrying the synapsin 1-luciferase construct displayed high levels of luciferase activity in the brain, spinal cord, and testis. Enriched populations of prepuberal types A and B spermatogonia and adult Leydig cells, pachytene spermatocytes, and round spermatids prepared from transgenic mice all displayed substantial luciferase activity. Thus, the rat synapsin 1 promoter can mediate reporter gene expression in neurons and testicular cell types.

How great is the risk of abuse in infants born to drug-using mothers?

UNLABELLED: This prospective, cohort study reports early child protection and surveillance process markers for children born to self-proclaimed drug-using mothers. BACKGROUND: A strong association is reported between maternal drug use and child abuse in North American studies. There are no systematic data describing this association for the UK population. Given the heterogeneous nature of drug cultures and associated behaviour it is difficult to generalize from US data to the UK population. METHODS: The study group consisted of all women referred to a hospital-based antenatal clinic for pregnant drug users. Infants of non-drug users were matched for social class and gestational age. At 18 months the Bristol and surrounding area child protection registers and child health surveillance records were searched. Infants were coded as to whether they were the subject of an enquiry, case conference, registration, registration with subsequent deregistration, or taken into care. RESULTS: There were 68 infants of drug users and 127 infants of non-drug users. Most (81%) of drug users were heroin and/or methadone users; half were using/had used intravenously. Child health surveillance uptake for both groups is lower than that reported for the Avon population as a whole during the study period, consistent with the relatively deprived populations represented. There is no statistically significant difference between the drug users and non-drug users. The overall risk of child protection proceedings was higher in children of drug users than in children of non-drug users. However, closer inspection of the data shows most of the excess risk is explained by the small group taken into care and the much larger group for whom the concerns were relatively shortlived as shown by their subsequent deregistration during the study period. CONCLUSIONS: Maternal drug use does not necessarily lead to unacceptable standards of parenting. More UK-based research is needed to inform the risk assessment process for child protection.

Parent education classes: teaching junior paediatric doctors and student nurses about normal baby care.

This paper describes the need for education on normal baby care and how a modified community parent education class was developed for junior doctors and student nurses. The aim was to increase their understanding of the subject and better able them to advise parents. The classes were developed by health visitors (HVs) and a National Child Birth Trust (NCT) counsellor. The evaluation results of a pilot are reported. Many benefits of interprofessional learning and teaching were identified.

The decision making process regarding the withdrawal or withholding of potential life-saving treatments in a children's hospital.

OBJECTIVES: To investigate the factors considered by staff, and the practicalities involved in the decision making process regarding the withdrawal or withholding of potential life-sustaining treatment in a children's hospital. To compare our current practice with that recommended by the Royal College of Paediatrics and Child Health (RCPCH) guidelines, published in 1997. DESIGN: A prospective, observational study using self-reported questionnaires. SETTING: Tertiary paediatric hospital. PATIENTS AND PARTICIPANTS: Consecutive patients identified during a six-month period, about whom a formal discussion took place between medical staff, nursing staff and family regarding the withholding or withdrawal of potentially life-sustaining treatments. The primary physician and primary nurse involved in the discussion were identified. METHOD: Two questionnaires completed independently by the primary physician and nurse. RESULTS: Twenty-two patients were identified (median age 1 year; range 1 day-34 years). In 20 cases treatment was withdrawn or withheld, in two cases treatment was continued. Nursing staff considered family wishes and family perceptions of patient suffering as significantly more important factors in decision making than medical staff, who considered prognostic factors as most important. In only two cases were the patient's expressed wishes apparently available. In most cases staff considered the patient's best interests were served and the process would not be enhanced by the involvement of an independent ethics committee. The exceptions were those cases in which treatment was continued following disagreement between parties. CONCLUSIONS: Our current practice is consistent with that recommended by the RCPCH. The contribution of the patient, provision of staff counselling and general practitioner (GP) involvement were identified as areas for improvement.

Too many pediatric trampoline injuries.

BACKGROUND: Recent reports note a dramatic increase in the number of pediatric trampoline injuries (PTI) during the past several years. In 1996, the US Consumer Product Safety Commission estimates that 83 000 patients received treatment for trampoline injuries in US hospital emergency departments (EDs), and that approximately 75% of these patients were <15 years of age. We sought to review our experience with PTI since our previous report (Pediatrics 1992;89:849), and to determine if the American Academy of Pediatrics' current (Pediatrics 1981;67:438) safety recommendations are adequate. METHODS: Retrospective medical record review of all PTI patients presenting to the pediatric ED from November 1990 through November 1997. RESULTS: A total of 727 PTI patients were included; medical records were unavailable for 3 patients. The annual number of PTI nearly tripled during the study period, from 51 in 1991 to a peak of 148 in 1996. PTI patients were 53% female, with a median age of 7 years; 37% were <6 years of age. Privately owned trampolines accounted for 99% of PTI. Most injuries (66%) occurred on the trampoline, 28% resulted from falls off, and 4% from imaginative mechanisms. One hundred eleven patients (15%) suffered severe injury (1990 Abbreviated Injury Scale value >/=3), usually of an extremity (89 out of 111). Fractures occurred in 324 patients (45%). Spinal injuries were common (12%), including 7 patients with cervical or thoracic fractures, and 1 with C7 paraplegia. Fractures were more frequently associated with falls off the trampoline, whereas spinal injuries more frequently occurred on the trampoline. Eighty patients (11%) required prehospital medical transport to our ED, 584 (80%) had ED radiographs, and 382 (53%) required pediatric surgical subspecialty involvement. Seventeen percent of PTI patients (125 out of 727) were admitted to the hospital, including 9 to the pediatric intensive care unit; 99 (14%) required one or more operations. Mean hospital stay was 2 days (range, 1-63 days); 24 stays (19%) were for >/=3 days. We estimate that the hospital charges for the acute medical care of PTI study patients at our institution totaled approximately $700 000. CONCLUSIONS: PTI are dramatically increasing in number, and result in considerable childhood morbidity. Most PTI occur on privately owned trampolines. Few, if any, safety recommendations for the trampoline are followed. We support recommendations for a ban on the recreational, school, and competitive pediatric use of trampolines.

Analysis and modulation of DNA repair in aging.

Nearly 40 years ago it was proposed that accumulation of mutations or increased levels of DNA damage might contribute to aging processes. Despite several correlative studies in this area, the answer as to whether genomic integrity contributes to aging has remained illusive. More recently it has been hypothesized that decreased mitochondrial DNA integrity plays a role in aging. To begin to test these hypotheses more directly, we are developing transgenic mouse and cell culture model systems. For example, transgenic mice overexpressing the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) have been made and have a reduced spontaneous frequency of hepatocellular carcinoma. A lifespan study using the MGMT transgenic mice is in progress in an effort to determine whether cancer impacts on the median or maximal lifespan of a species. Second, a quantitative PCR technique is being used to measure mitochondrial DNA damage in mitotic and post-mitotic cells to determine if the level of damage and/or repair is different based on mitotic status. Finally, mice deficient in metallothionein-I and -II are being used in an effort to determine if the subcellular distribution of metals impact on oxidative damage with increased age.

Calcium concentration-dependent mechanisms through which ketamine relaxes canine airway smooth muscle.

BACKGROUND: Ketamine is a potent bronchodilator that, in clinically used concentrations, relaxes airway smooth muscle in part by a direct effect. This study explored the role of calcium concentration (Ca2+) in this relaxation. METHODS: Canine trachea smooth muscle strips were loaded with the fluorescent probe fura-2 and mounted in a spectro-photometric system to measure force and intracellular calcium concentration ([Ca2+]i) simultaneously. Calcium influx was estimated using a manganese quenching technique. Cyclic nucleotides in the airway smooth muscle strips were measured by radioimmunoassay. RESULTS: In smooth muscle strips stimulated with submaximal (0.1 microM) and maximal (10 microM) concentrations of acetylcholine, ketamine caused a concentration-dependent decrease in force and [Ca2+]i. The sensitivity of the force response to ketamine significantly decreased as the intensity of muscarinic receptor stimulation increased; the median effective concentration for relaxation induced by ketamine was 59 microM and 850 microM for tissue contracted by 0.1 microM or 10 microM acetylcholine, respectively (P < 0.05). In contrast, the sensitivity of the [Ca2+]i response did not depend on the intensity of muscarinic receptor stimulation. Ketamine at 1 mM significantly inhibited calcium influx. Ketamine did not significantly increase cyclic nucleotide concentrations. CONCLUSIONS: Ketamine-induced relaxation of canine airway smooth muscle is associated with a decrease in [Ca2+]i and calcium influx, effects that are not mediated by an increase in cyclic nucleotides; and the sensitivity of the force response to ketamine decreases as the level of preexisting muscle tone increases, an effect that is not explained by differential effects on [Ca2+]i.

Xrcc-1 expression during male meiosis in the mouse.

XRCC1 is involved in DNA strand-break repair, homologous recombination, and sister chromatid exchange and is expressed as a low-abundance mRNA with elevated expression in testis. The purpose of this study was to determine whether specific spermatogenic cell types have elevated Xrcc-1 expression and whether expression levels change in the testis with increased age. Northern blot analysis of mRNA prepared from testes of 15-, 25-, and 60-day-old mice revealed a single hybridizing band of 2.2 kb. Quantitative RNase protection assays revealed no changes in the level of Xrcc-1 expression in testis relative to DNA content among 6-, 12-, 18-, 24-, or 28-mo-old mice. Finally, reverse transcription coupled polymerase chain reaction amplification results demonstrated that Xrcc-1 expression is most abundant in pachytene spermatocytes and round spermatids with low expression in Sertoli cells, types A and B spermatogonia, preleptotene spermatocytes, and leptotene plus zygotene spermatocytes. The relatively abundant Xrcc-1 expression in pachytene spermatocytes and round spermatids suggests that Xrcc-1 is involved in DNA strand-break repair associated with meiotic recombination in addition to its previously implicated role in strand-break repair associated with base excision repair.

A comparison of the brain weights of normal, untreated hydrocephalic and treated hydrocephalic rat pups.

The dry brain weights of normal, untreated and treated hydrocephalic pups of Texas, Lewis and Texas/Lewis cross rats aged from 2 to 60 days were compared using the technique of generalised linear modelling. It was found that with increasing age there is a steadily progressive increase in the weight of the brains of the normal animals. The brains of the untreated hydrocephalics showed a normal increase in weight up to about the 25th day but after that whilst the weight continued to increase, it was significantly less than normal. On the other hand the weight gain of the brains of the treated hydrocephalic pups resembled that of the normals and steadily increase in weight throughout the period of observation.

Studies of tamoxifen as a promoter of hepatocarcinogenesis in female Fischer F344 rats.

Tamoxifen, an antiestrogen used in the treatment of breast cancer, was assessed for carcinogenic potential in the two-stage model of experimental hepatocarcinogenesis. Groups of female Fisher F344 rats were initiated with a non-necrogenic, subcarcinogenic dose of diethylnitrosamine (DEN; 10 mg/kg, po) and fed tamoxifen at a concentration of 250 mg per kg of AIN-76A diet for 6 or 15 months. The livers of these animals exhibited an increase in size and number of altered hepatic foci compared with those animals which were initiated with DEN but not exposed to tamoxifen. This finding indicates that tamoxifen may have a carcinogenic potential in the rat liver. After 6 months of treatment, neoplastic nodules were observed in 3/8 rats in the DEN-initiated, tamoxifen-treated group. In the initiated group provided with tamoxifen for 15 months, neoplastic nodules were observed in 7/8 rats and hepatocellular carcinomas in 3/8 rats. The serum level of tamoxifen in these rats was 200-300 ng/ml. The ratio of tamoxifen, 4-hydroxy tamoxifen, and N-desmethyl tamoxifen was 1:0.1:0.5-1 in the serum. When adjusted for age-related weight increases, the serum and liver levels of tamoxifen and its N-desmethyl metabolite did not change over the 15 months. In the rat liver, the level of tamoxifen and its N-desmethyl metabolite was 10-29 micrograms/g liver after 6 or 15 months of chronic dietary administration. The ratio of tamoxifen:4-hydroxy tamoxifen:N-desmethyl tamoxifen was 1:0.1.3-3.3 in the liver. Therefore, the liver had 20- to 30-fold more tamoxifen and 4-hydroxy tamoxifen and at least 100-fold more N-desmethyl tamoxifen than the serum (assuming 1 gram of tissue is equivalent to 1 ml of serum). These results indicate that tamoxifen is a promoting agent for the rat liver at serum levels found in patients given the usual therapeutic course of tamoxifen. The high concentrations of tamoxifen attained in the rat liver indicate that actions other than its known estrogenicity for liver could contribute to its promoting action. In addition, these results indicate that the pharmacodynamic differences in tamoxifen metabolism in rats and humans and at low versus high doses should be determined. Thus, the therapeutic indications for tamoxifen should be balanced by the potential risk it may present as a promoting agent in mammalian liver.

Polycyclic aromatic hydrocarbon solute probes. Part II. Effect of solvent polarity on the fluorescence emission fine structures of coronene derivatives.

The fluorescence properties of coronene (Co), benzo[a]coronene (BCo), naphtho[2,3-a]coronene (NCo), dibenzo[a,j]coronene (DCo), naphtho[1,2,3,4-ghi]perylene, benzo[pqr]naphtho[8,1,2-bcd]perylene and dibenzo[cd,lm]perylene dissolved in solvents of varying polarity are reported. Measurements indicated that the emission intensities of the four coronene derivatives depended on solvent polarity. The Co, BCo and NCo scales have been defined as the ratio of the fluorescence intensities of bands I and III of the vibronic spectra. Band III of dibenzo[a,j]coronene was not clearly identifiable in all the solvents studied, and the DCo scale was therefore defined as the intensity ratio of band I and IV. Emission intensity ratios of the three perylene derivatives remained nearly constant, irrespective of solvent polarity.

Double-blind comparison of half-dose and standard-dose flupenthixol decanoate in the maintenance treatment of stabilised out-patients with schizophrenia.

A double-blind controlled trial of 50% dose reduction in maintenance treatment in stable out-patients with low BPRS scores and good social function shows a significantly higher relapse rate in the low-dose group at 12 months (P less than 0.05). After an interval of 24-36 months from dose reduction, 56-76% had experienced a relapse and 76-79% had resumed their former dosage. No clear advantage was shown for the lower dose in either a reduction of side-effects or improved social function, but a reduced prevalence or lower rate of symptom emergence for tardive dyskinesia was suggested.