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Biomedical subjects

H Leonard

Publications and source records attributed to H Leonard.

At least 55 records · Page 3Linked to original sources
PubMed1999

Patterns of pregnancy loss, perinatal mortality, and postneonatal childhood deaths in families of girls with Rett syndrome.

Rett syndrome is a neurodevelopmental disorder that occurs predominantly in girls and results in severe physical and intellectual handicap. A popular genetic mechanism is an X-linked dominant disorder, lethal in males. A case control study design was used to investigate fetal wastage as indicated by reported miscarriage and stillbirth prevalence, and the prevalence and cause of reported neonatal and other childhood deaths. There was no disturbance in the sibling sex ratio when case and control families were compared. In the parental generation and in the proband generation miscarriages were reported in similar proportions in case and control families. The reported stillbirth rates in case families was almost double that in control families and reported perinatal loss was more common on the maternal side in case families than in control families. Stillbirths and neonatal deaths affected slightly more boys in the parental and proband generations of case families (19 of 30) than in control families (10 of 21). Childhood deaths also occurred a little more commonly in Rett syndrome families. Sudden infant death syndrome was reported in three siblings of Rett syndrome probands but in no control siblings. Confirmation of this pattern of perinatal loss and infant mortality could indicate an alternative expression of the Rett syndrome gene.

Abortion, Spontaneous↗
PubMed1998

Diagnosis of Rett syndrome: can a radiograph help?

Rett syndrome (RS), a neurodevelopmental disorder almost exclusively affecting girls, is associated with severe intellectual and motor disability. In the absence of biological markers, diagnosis is determined by a set of clinical criteria. In a previous study in Scotland, shortening of the fourth metatarsal was reported clinically in 20% of classical RS cases aged 5 years or older. The Australian Rett Syndrome Study database has facilitated a population-based radiological study of the hands and feet of girls with RS. Straight radiographs of hands and feet were available from 94 cases, representing 70.1% of the known RS population in Australia. Control radiographs were matched for age, sex, and laterality. Relative shortening of the fourth metacarpal/metatarsal was assessed using the sign method. A short ulna (negative ulna variance) was defined as the distal articular surface of the ulna being at least 5mm proximal to the distal articular surface of the radius. A positive metacarpal sign was twice as common in verified cases of RS than in controls in the right but not the left hand. A short ulna was more common in subjects with RS than in controls. A short fourth metatarsal was also more common among subjects with RS. More than half (56.6%) the girls with RS over the age of 4 years had a negative ulnar variance in either wrist or a metatarsal sign in either foot. These findings will assist with the diagnosis of RS and may help direct research towards the location of the molecular defect.

Adolescent↗
PubMed1998

Rett syndrome: significant clinical overlap with Angelman syndrome but not with methylation status.

Rett syndrome and Angelman syndrome are neurodevelopmental disorders characterized by severe intellectual disability, microcephaly, speech disturbance, movement disorders with gait and/or truncal ataxia, and occasionally a similar facial appearance. Both conditions can be difficult to diagnose in girls early in their clinical course and can be difficult to distinguish from each other. Genomic imprinting is a known association in Angelman syndrome and previously has been suggested in Rett syndrome. Our aim was to evaluate the methylation status in a cohort of classical patients with Rett syndrome, using a methylation system for chromosome 15q11-13. Methylation analysis of chromosome 15 has not been previously reported in Rett syndrome. Furthermore, we document the clinical features of 31 girls with classical Rett syndrome and confirm the phenotypic similarities between Rett syndrome and Angelman syndrome. The methylation studies in these girls with Rett syndrome were normal. This excludes an imprinting error of the Angelman syndrome critical region on chromosome 15 (15q11-13) as an association with Rett syndrome, and indicates that methylation studies may be useful in distinguishing Rett syndrome from Angelman syndrome in young patients with an overlapping clinical phenotype. A normal methylation pattern, however, does not exclude the diagnosis of Angelman syndrome and clear distinction between the two syndromes will evolve over time.

Adolescent↗
PubMed1998

Is the girl with Rett syndrome normal at birth?

The diagnosis of Rett syndrome is currently determined by a series of criteria, the first three of which are concerned with the initial period of normality. Using the Australian Rett Syndrome Database, information about this early period was obtained by questionnaires to paediatricians and families. For girls born between 37 and 42 weeks' gestation, 70.7% of girls with Rett syndrome had birthweights <3500g compared with 62.2% of singleton births of the same gestational age in Western Australia between 1980 and 1992. The mean head circumference at birth for infants with Rett syndrome was lower than the mean head circumference at birth for the reference populations after accounting for gestational age. Forty-one percent of parents reported that their daughter had some perinatal difficulty, while in 22.4% of cases clinicians reported some perinatal abnormality. In 46.5% of girls, parents reported that their daughter's development or behaviour had been unusual in the first 6 months. Our results provide further evidence that the girl with Rett syndrome may not be normal at birth.

Adolescent↗
PubMed1997

Quantitative determination of theophylline by an automated chemiluminescent immunoassay in serum and plasma: comparison to other methods of analysis.

A chemiluminescent immunoassay for theophylline in serum or plasma was developed for the Ciba Corning ACS: 180 automated analyzer. The assay has a limit of quantitation of 0.2 microgram/ml, with a range up to 40 micrograms/ml. The cross-reactivity to metabolites 1,3-dimethyluric acid 3-methylxanthine was 3.4% and 2.5%, respectively. Overall means of 101.0% and 97.8% were determined from dilution linearity and addition studies, respectively. When compared to a high-performance liquid chromatography (HPLC) method, a linear regression of ACS Theophylline = 0.996 (HPLC) + 0.35, r = 0.991, n = 93, was obtained. Similar results were obtained when the ACS assay was compared to other immunoassays. Precision (within-run and total coefficient of variation or CV) was < 6% in the therapeutic range (10-20 micrograms/ml). The performance data demonstrate that the ACS Theophylline assay provides an additional choice for the clinical measurement of the drug.

Chromatography, High Pressure Liquid↗
PubMed1997

The prevalence and incidence of Rett syndrome in Australia.

The Australian Paediatric Surveillance Unit and the Rett Syndrome Association of Australia (a parent support group) were the main sources of ascertainment of cases of Rett syndrome (RS) aged 18 years or less in Australia. Further information was obtained from questionnaires to paediatricians and families. Cases were categorised as classical, atypical, potential or non-verifiable, using internationally recognised criteria. Capture recapture methods were used to adjust prevalence measures for missing cases, and Kaplan Meier survival analysis to estimate cumulative incidence. A total of 134 cases of RS was identified, and of those over 5 years of age, 68% were classical and 32% were atypical. The adjusted prevalence was 0.72 per 10,000 females, and the cumulative incidence was 0.96 per 10,000 females to age 12 years. The prevalence was similar to that in Sweden and Scotland, but higher than in Texas. Comparing successive birth cohorts, there was evidence to suggest that RS is being diagnosed earlier and that more cases are being diagnosed as atypical.

Adolescent↗
PubMed1996

Family planning requirements in the adult congenital heart disease clinic.

OBJECTIVE: To determine whether women with congenital heart disease were receiving appropriate advice on contraception. SETTING: Adult congenital heart disease clinic in a tertiary cardiac referral centre. DESIGN: Questionnaire administered to 35 consecutive female patients attending the adult congenital clinic. The cardiologist assessed what the risk would be if each patient used an oestrogen containing contraceptive pill (OCP). RESULTS: Of the 33 patients admitted to the study 6 patients thought their heart condition precluded them from taking an OCP when in fact it did not and 3 incorrectly said that an OCP would be suitable for them. Three women with relatively minor lesions had been incorrectly denied the OCP and 2 further patients were using inappropriate methods. There had been 6 unwanted pregnancies in the total group. CONCLUSIONS: Many women with congenital heart disease do not know the most appropriate method of contraception for them or have received incorrect advice. It is often patients with less severe lesions who receive the most inappropriate advice. It is clear that the family planning needs of this population are currently poorly catered for. Each unit must ensure that the information necessary in making informed decisions on contraception is available to the doctor advising on family planning.

Adolescent↗
PubMed1995

Skeletal abnormalities in Rett syndrome: increasing evidence for dysmorphogenetic defects.

The presence of metatarsal and metacarpal abnormalities in some individuals has raised the possibility that Rett syndrome is, in fact, a multiple congenital abnormalities/mental retardation (MCA/MR) syndrome. We have conducted radiological examination of 17 cases of Rett syndrome in Western Australia. Short fourth and/or fifth metatarsals were identified in 65% of cases and short fourth and/or fifth metacarpals in 57%. Metatarsal (P = 0.045) and metacarpal (P = 0.006) shortness were significantly more common in girls 14 years or older. Negative ulnar variance (found in 79% of cases) appeared to be independent of age. Reduced bone density in the hands was found in 86% of cases. A nationwide study using the Australian Rett Syndrome Database is planned to follow up these findings and compare them with findings from a control group. The confirmation of these abnormalities in a high proportion of cases may provide morphologic markers to assist in the diagnosis of Rett syndrome and perhaps provide a further avenue of research into the pathogenesis of this disorder.

Abnormalities, Multiple↗
PubMed1995

Current knowledge of medications for the treatment of childhood anxiety disorders.

OBJECTIVE: This report will review the costs, risks, and benefits of potentially useful medications for the treatment of children and adolescents with anxiety disorders and will identify areas where data are limited and additional research is needed. METHOD: A Medline-assisted review of the literature was performed. Attention was given to dosage, response, and side effects of medications. Wherever possible, blinded, controlled medication trials in children with anxiety disorders (diagnosed by structured criteria) were targeted for use as the primary references. Relatively few systematic studies were found, so information from open trials and case reports also was included, as were controlled trials in adult populations. RESULTS: The largest body of work supporting the use of medications for childhood anxiety came from studies of obsessive-compulsive disorder, where clomipramine and fluoxetine have been found effective in systematic studies. In other childhood anxiety disorders, there are conflicting data about the efficacy of medications, such as tricyclic antidepressants, benzodiazepines, serotonin reuptake inhibitors, beta-blockers, and monoamine oxidase inhibitors. CONCLUSIONS: This review of the systematic pharmacological trials for childhood anxiety disorders revealed only 13 controlled studies: 5 for obsessive-compulsive disorder, 4 for school refusal/separation anxiety disorder, and 4 for avoidant/overanxious disorder or mixed diagnostic groups. Medications appear to be helpful for childhood anxiety disorders, although definitive pharmacotherapeutic data are lacking for many conditions. A systematic study of these medications is required to establish safety and efficacy in the pediatric age group. Evolving diagnostic criteria and terminology, the presence of comorbid diagnoses (especially affective disorders), and inadequate medication dosages may be factors hindering research in this field. Until additional research is done, clinicians must carefully consider the relative risk-to-benefit ratio when prescribing these medications.

Adolescent↗
PubMed1993

Sensitivity of the Diagnostic Interview Schedule for Children, 2nd edition (DISC-2.1) for specific diagnoses of children and adolescents.

OBJECTIVE: The sensitivity of the Diagnostic Interview Schedule for Children, second edition (DISC-2.1) was examined for certain "rare" disorders: eating disorders, major depressive episode, obsessive compulsive disorder, psychosis, tic disorders, and substance use disorders. METHOD: Subjects recruited from specialized centers were interviewed with the DISC-2.1; the centers' diagnoses served as the criterion measure. RESULTS: Overall the DISC showed good to excellent sensitivity (range = 0.73 to 1.0). Used alone, the DISC-P (parent interview) was generally more sensitive than the DISC-C (child interview). Areas for additional instrument revision were identified. Recommendations about informant choice by diagnosis are offered. CONCLUSIONS: The strategy used in this study was useful for assessing the DISC's sensitivity for these disorders. Additional work examining specificity of the DISC remains to be done. The DISC should prove a useful adjunct in clinical settings given the ease and relatively low cost of administration.

Adolescent↗
PubMed1992

Immunoepidemiology of Ascaris lumbricoides: relationships between antibody specificities, exposure and infection in a human community.

The serum antibody responses of 124 people naturally exposed to Ascaris lumbricoides infection were analysed by immunoprecipitation of radio-isotope labelled 3rd- and 4th-stage larval Ascaris suum excretory and secretory antigens (L3/4 ES). Profiles of antigens recognized were visualized by polyacrylamide gel electrophoresis (SDS-PAGE), and the band intensities of the 12 major precipitated antigens were individually scored. Most subjects were seropositive, but considerable variation was observed in the amount of total and individual ES antigens precipitated. The sex- and age-related profiles of antibody levels followed similar patterns to those of egg output. In addition, total antibody scores of individuals were closely correlated (r = 0.47-0.52) with their eggs per gram of faeces (e.p.g.) collected 4 months after blood samples were taken. These findings suggest that antibody levels against larval ES antigens reflect recent exposure and are consistent with the hypothesis that establishment of adult worms is proportional to the number of larvae that recently migrated through the lung.

Adolescent↗
PubMed1992

Rates of Obsessive Compulsive Disorder in first degree relatives of patients with trichotillomania: a research note.

To explore a possible relationship between trichotillomania, (TTM) (compulsive hair pulling) and Obsessive Compulsive Disorder (OCD), 65 out of 69 (94%) first degree relatives of 16 female probands with severe chronic TTM were compared with two control groups for OCD and for TTM. Three (19%) of the 16 TTM probands had at least one first degree relative with a lifetime history of OCD, and there was an age corrected rate of 6.4% of first degree relatives with OCD. No relative in control group (A) met criteria for OCD. There was a trend (Fishers exact p = .07, two tailed) for a higher rate (age corrected) of OCD in TTM families; these pilot data are consistent with the concept of a spectrum of obsessive compulsive disorders which includes TTM and other pathological grooming behaviours.

Adolescent↗
PubMed1990

CSF somatostatin in childhood psychiatric disorders: a preliminary investigation.

Disruptive behavior disorders and obsessive-compulsive disorder have been associated with serotonergic dysfunction as well as particular body habitus findings in pediatric patients. Somatostatin, a peptide which stimulates serotonin release and inhibits growth hormone release, was measured in the cerebrospinal fluid (CSF) of 10 children with disruptive behavior disorders and in 10 age-, sex-, and race-matched pairs of obsessive-compulsive disorder patients. Decreased concentrations of somatostatin were found in disruptive behavior disorder patients relative to obsessive-compulsive children, even after controlling for differences in Tanner stage. In contrast to studies in adults, those patients in a depressed state did not have lower CSF somatostatin concentration.

Adolescent↗
PubMed1990

Psychiatric disorders in first degree relatives of children and adolescents with obsessive compulsive disorder.

One hundred and forty-five first-degree relatives (89 parents [96%] and 56 siblings [98%]) of 46 children and adolescents with severe primary obsessive compulsive disorder (OCD) were personally interviewed with clinical and structured psychiatric interviews. Parent interviews were scored by a rater blind to proband diagnosis. Thirty percent of probands had at least one first-degree relative with OCD: 25% of fathers and 9% of mothers received this diagnosis. Forty-five percent of fathers and 65% of mothers received one or more other psychiatric diagnoses. The increased familial rate of OCD over that expected from a general population, and over that found in parents of conduct disordered patients, is consistent with a genetic factor in OCD. Presenting obsessive compulsive symptoms of probands and their parents were usually dissimilar, arguing against any simple social or cultural transmission.

Adolescent↗
PubMed1989

Obsessive-compulsive disorder in children and adolescents. Clinical phenomenology of 70 consecutive cases.

We reviewed the phenomenology of obsessive-compulsive disorder (OCD) in 70 consecutive children and adolescents studied prospectively at the National Institute of Mental Health, Bethesda, Md, between 1977 and 1987. There is striking similarity between the clinical presentation of OCD in children and in adult patients. Washing, grooming, and checking rituals and/or preoccupation with disease, danger, and doubt account for the great majority of cases. Twenty-five percent of subjects had a first-degree relative with OCD. The fixed content and style of symptoms within and across subjects, and the identical presentation across a wide age range, suggest an ethological model for OCD.

Adolescent↗