PubMed Health⌕ Search

Biomedical subjects

S Creighton

Publications and source records attributed to S Creighton.

At least 19 recordsLinked to original sources
PubMed2006

Parental perspectives on the causes of an autism spectrum disorder in their children.

Autism Spectrum Disorders (ASDs) are complex neurodevelopmental disorders with many biological causes, including genetic, syndromic and environmental. Such etiologic heterogeneity impacts considerably upon parents' needs for understanding their child's diagnosis. A descriptive survey was designed to investigate parental views on the cause(s) of ASD in their child. Among the 41 parents who replied to the questionnaire, genetic influences (90.2%), perinatal factors (68.3%), diet (51.2%), prenatal factors (43.9%) and vaccines (40.0%) were considered to be the most significant contributory factors. Parents reported inaccurately high recurrence risks, misperceptions of the contribution of various putative factors, feelings of guilt and blame regarding their child's diagnosis, as well as a lack of advocacy for genetic counseling by non-geneticist professionals. This study offers clinicians and researchers further insight into what parents believe contributed to their child's diagnosis of ASD and will help facilitate genetic counseling for these families.

Autistic Disorder↗
PubMed2006

Predictive testing for Huntington disease: interpretation and significance of intermediate alleles.

Direct mutation analysis for Huntington disease (HD) became possible in 1993 with the identification of an expanded CAG trinucleotide repeat as the mutation underlying the disease. Expansion of CAG length beyond 35 repeats may be associated with the clinical presentation of HD. HD has never been seen in a person with a CAG size of <36 repeats. Intermediate alleles are defined as being below the affected CAG range but have the potential to expand to >35 CAG repeats within one generation. Thus, children of intermediate allele carriers have a low risk of developing HD. Currently, the intermediate allele range for HD is between 27 and 35 CAG repeats. In this study, we review the current knowledge on intermediate alleles for HD including the CAG repeat range, the intermediate allele frequency, and the clinical implications of an intermediate allele predictive test result. The factors influencing CAG repeat expansion, including the CAG size of the intermediate allele, the sex and age of the transmitting parent, the family history, and the HD gene sequence and haplotype, will also be reviewed.

Age Factors↗
PubMed2006

Reactivation of latent hepatitis B virus infection with HIV-related immunosuppression.

The effect of HIV-related immunosuppression and antiretroviral therapy on the reactivation of latent hepatitis B virus (HBV) infection is unclear. We report four patients with advanced HIV-related immunosuppression and abnormal liver function tests who had evidence of HBV reactivation. Reclearance of hepatitis B occurred in two cases with HIV treatment regimens not containing lamivudine, suggesting that improved immune function may be responsible. In three cases, HBV reactivation was recognized during investigation for abnormal liver function initially attributed to drug toxicity. The possibility of HBV reactivation must be considered in the differential diagnosis of abnormal liver function in cases with advanced HIV.

Antiretroviral Therapy, Highly Active↗
PubMed2005

A variant Cri du Chat phenotype and autism spectrum disorder in a subject with de novo cryptic microdeletions involving 5p15.2 and 3p24.3-25 detected using whole genomic array CGH.

Cri du Chat syndrome (CdCs) is a well-defined clinical entity, with an incidence of 1/15,000 to 1/50,000. The critical region for CdCs has been mapped to 5p15, with the hallmark cat-like cry sublocalized to 5p15.3 and the remaining clinical features to 5p15.2. We report findings in a subject with a de novo t(5;7)(p15.2;p12.2) and an inv(3)(p24q24), who was found to have a cryptic microdeletion in the critical region for CdCs detected using a 1-Mb genomic microarray. In addition to 5p deletion, the proband had a de novo single clone loss at the 3p breakpoint of inv(3)(p24q24) and a familial single clone deletion at 18q12. Deletions were confirmed using microsatellite analysis and fluorescence in situ hybridization. The 5p deletion encompasses approximately 3 Mb, mapping to the border between bands 5p15.2 and 5p15.31. The single clone deletion on chromosome 3 maps to 3p24.3-3p25, for which there is no known phenotype. The clinical features of our proband differ from the characteristic CdC phenotype, which may reflect the combined effect of the two de novo microdeletions and/or may further refine the critical region for CdCs. Typical features of CdCs that are present in the proband include moderate intellectual disability, speech, and motor delay as well as dysmorphic features (e.g. broad and high nasal root, hypertelorism, and coarse facies). Expected CdCs features that are not present are growth delay, microcephaly, round facies, micrognathia, epicanthal folds, and the signature high-pitched cry. Behavioral traits in this subject included autism spectrum disorder, attention-deficit hyperactivity disorder, and unmanageable behavior including aggression, tantrums, irritability, and self-destructive behavior. Several of these behaviors have been previously reported in patients with 5p deletion syndrome. Although most agree on the cat-cry critical region (5p15.3), there is discrepancy in the precise location and size of the region associated with the more severe manifestations of CdCs. The clinical description of this proband and the characterization of his 5p deletion may help to further refine the phenotype-genotype associations in CdCs and autism spectrum disorder.

Adolescent↗
PubMed2005

Is ritonavir boosting associated with gout?

Asymptomatic hyperuricaemia is associated with ritonavir therapy, but gout has rarely been reported. We present a retrospective cohort study of 1825 HIV-positive patients seen at one inner London HIV clinic over a two-year period. In all, 18 patients had gout, of whom 15 were receiving antiretroviral therapy. Seven had predisposing risk factors for gout (e.g. pyrazinamide therapy, haematological malignancy). Of the remaining 11 patients, two were on no medication and eight (73%) were receiving ritonavir as a boosted protease inhibitor (PI). By comparison, 11% of HIV-positive patients without gout were receiving ritonavir (odds ratio = 22; confidence interval = 5-104). Seven of the 18 patients had documented features of lipodystrophy and dyslipidaemia. Gout was seen in patients with known risk factors for gout or who were receiving ritonavir as a boosted PI and who also had lipodystrophy.

Gout↗
PubMed2003

Predictive, pre-natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987 to 2000.

Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known prior family history of HD.

Adolescent↗
PubMed2003

Pregnancy after lower urinary tract reconstruction for congenital abnormalities.

OBJECTIVE: To evaluate the effect of pregnancy on renal function, and the effect of congenital urinary tract abnormality and reconstruction on pregnancy and delivery. PATIENTS AND METHODS: The case notes were reviewed of 20 women (median age 32.5 years) who had had 29 live babies. Data collected included patient demographics, congenital urological abnormality, urological reconstructive procedure(s) and any subsequent urological complications. Pregnancy details, including urological and obstetric complications, presentation and mode of delivery, were obtained via a postal questionnaire from the relevant obstetrician. RESULTS: Seven patients had exstrophy-epispadias, seven spinal dysraphism, two sacral agenesis, and one each cerebral palsy, epispadias, imperforate anus and small bladder with vesico-ureteric reflux and congenital incontinence. They had had a mean (range) of 5.7 (1-12) urological reconstructive procedures each. Patients with exstrophy-epispadias had significantly more operations (mean 7.8) than those with spinal dysraphism (mean 4.14) or other diagnoses (mean 2.6) (P < 0.01). At the last follow-up 13 patients had an enterocystoplasty, six a neobladder and one an ileal conduit. Pregnancy-related urological complications were urinary tract infection in 15, upper tract obstruction requiring nephrostomy and stent in three, Mitrofanoff difficulties in two and pyelonephritis in one. There was no significant deterioration in glomerular filtration rate or serum creatinine after pregnancy. Only 10 of the births were normal or assisted vaginal deliveries. Seven patients had emergency and 12 had elective Caesarean sections for obstetric indications, including four breech births in the seven patients with vesical exstrophy. CONCLUSIONS: Pregnancy has no long-term effect on renal function and does not compromise reconstruction. Although there is a substantial complication rate and an increased need for Caesarean section, pregnancy in women with lower urinary tract reconstruction for congenital urological abnormalities is ultimately safe for both mother and baby. Interdisciplinary co-operation is desirable for a successful outcome.

Adult↗
PubMed2003

Long-term gynecological outcome of patients with persistent cloaca.

PURPOSE: Persistent cloaca is a complex malformation that remains a difficult reconstructive challenge, and data on long-term outcome are scarce. Gynecological abnormalities are common with cloaca but may remain asymptomatic until puberty or adult life. We evaluate long-term gynecological sequelae in these patients with persistent cloaca. MATERIALS AND METHODS: The records and radiographs of postpubertal patients (mean age 16.8 years, range 10 to 32) treated for cloacal malformation at 1 institution from 1970 to 2001 were retrospectively reviewed. Outcome data at puberty were available in 41 patients. Of the patients 24 are currently older than 16 years and outcome data for sexual activity were available in 21 with 3 lost to followup. RESULTS: All 41 patients were evaluated at puberty, and 28 (68%) had uterine function, 13 (32%) were menstruating normally and 15 (36%) presented with hematometra/hematocolpos. All 15 girls with an obstructed uterus required surgery, which included hysterectomy in 2, partial hysterectomy with vaginoplasty in 3 and vaginoplasty in 9. There was 1 complex case of fistula. Etiology of the obstructed uterus was vaginal stenosis after reconstruction in 3 cases, stenosis of persistent urogenital sinus (no previous reconstruction) in 11 and cervical stenosis in 1. Ten patients experienced primary amenorrhoea, which was confirmed in 8 (20%) while 2 (5%) continue to be followed for possible cryptic obstruction. In 10 girls the diagnosis of absent/vestigial uterus was made at early laparotomy but this was erroneous in 6 in whom uterine function developed at puberty. Of the 21 older girls (age at review 17 to 32 years, mean 24) 12 are or have been sexually active and 6 have been examined by a gynecologist and have an adequate vagina but are not sexually active. To date 4 patients have required revision vaginal surgery in adulthood to facilitate intercourse (re-do vaginoplasty in 3, introitoplasty in 1). One woman has postponed vaginal reconstructive procedures and 2 others are currently being followed. There have been no pregnancies in this series to date. CONCLUSIONS: Patients born with persistent cloaca have a high incidence of gynecological problems at the onset of menses and in early adult life. Therefore, it is necessary to reassess these girls at early puberty by ultrasound/magnetic resonance imaging and vaginoscopy. Additional surgery may then be necessary to create a vagina for menstruation and sexual intercourse.

Adolescent↗
PubMed2002

News from the frontline: sexually transmitted infections in teenagers attending a genitourinary clinic in south east London.

OBJECTIVES: To define the incidence and characterise the clinical presentation of sexually transmitted infections (STI) in people aged <or=16 years old attending a genitourinary clinic in south east London. METHODS: Cross sectional analysis of clients aged <or=16 years attending one genitourinary clinic. A subgroup was identified for priority treatment. Data collected included age, reason for presentation, diagnosis, contraceptive use, and adherence to therapy. Diagnoses were compared to the KC60 codes for female attendances of all ages. RESULTS: 144 females and 18 males with a mean age of 15.4 years attended, of whom 49% were symptomatic. Compared to other attenders, clients aged <or=16 years were significantly more likely to have an STI (64% versus 22%, p <0.00000001); 27 were pregnant (of whom 96% requested a termination of pregnancy); 47% did not return for follow up; and 12% did not adhere to treatment plan. Those diagnosed with an STI were significantly less likely to reattend (p<0.001). CONCLUSIONS: There is a high rate of STIs in 16 year olds compared to national figures and to general clinic attenders. Poor contraception is often overlooked within the genitourinary medicine clinic. Young attenders frequently fail to reattend for follow up. Priority treatment did not affect outcome. Further strategies are needed to identify ways to improve young people's access to genitourinary medicine clinics.

Adolescent↗
PubMed2001

Managing intersex.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed2001

Magnetic resonance imaging in the assessment of complex Müllerian anomalies.

OBJECTIVE: To evaluate the accuracy of magnetic resonance imaging in assessment of adolescent patients with complex Müllerian anomalies and its contribution towards operative management. DESIGN: A retrospective review of magnetic resonance imaging and operative findings. SETTING: A London teaching hospital that is a tertiary referral centre for complex reproductive tract disorders. SAMPLE: All adolescents referred for assessment of complex Müllerian anomalies, from 1996 to 1999, and undergoing both magnetic resonance imaging and surgical assessment. METHOD: In the nine suitable patients magnetic resonance imaging and surgical findings were compared and the role of magnetic resonance imaging in determining the route and type of surgery was evaluated. MAIN OUTCOME MEASURES: Magnetic resonance imaging data on reproductive tract anatomy and surgical findings detailing reproductive tract anatomy. RESULTS: There was good correlation of magnetic resonance imaging and operative findings in all cases. The best correlation was with uterine structure. In four cases the magnetic resonance imaging findings were essential for the appropriate choice of the surgical approach and type of procedure. CONCLUSIONS: Magnetic resonance imaging is a valuable tool in the management of this particular complex group of patients.

Adolescent↗
PubMed2001

Surgery for intersex.

Explore the source record for details and available documents.

Adaptation, Psychological↗
PubMed2000

Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism.

Retinoids, particularly all-trans-retinoic acid (RA), are potent regulators of cell differentiation, cell proliferation, and apoptosis. The role of all-trans-RA during development and in the maintenance of adult tissues has been well established. The control of all-trans-RA levels in cells and tissues is regulated by the balance between its biosynthesis and its catabolism to inactive metabolites. The cytochrome P450 enzyme P450RAI (herein renamed P450RAI-1) is partially responsible for this inactivation of all-trans-RA. In this report, we describe the identification, molecular cloning, and characterization of a second related enzyme, P450RAI-2, which is also involved in the specific inactivation of all-trans-RA. Transiently transfected P450RAI-2 can convert all-trans-RA to more polar metabolites including 4-oxo-, 4-OH-, and 18-OH-all-trans-RA. Competition experiments with other retinoids suggest that all-trans-RA is the preferred substrate. The high level of expression of P450RAI-2, particularly in the cerebellum and pons of human adult brain, suggests a unique role for this enzyme in the protection of specific tissues from exposure to retinoids.

Amino Acid Sequence↗
PubMed1995

Gel kinetic analysis of DNA polymerase fidelity in the presence of proofreading using bacteriophage T4 DNA polymerase.

A gel fidelity assay, previously used in the analysis of DNA polymerases having no associated 3' to 5' exonuclease activity, has been generalized for use with polymerases that contain exonucleolytic proofreading. The main purpose of this study was the development of a general analysis, using a standard Markov model, to convert experimentally observed DNA primer gel bands arising from insertion and proofreading of right and wrong deoxyribonucleotides, into nucleotide incorporation velocities and, most importantly, fidelities. The model has been applied primarily to an analysis of polymerase kinetics and fidelity in the presence of a next correct rescue dNTP, but the model can be conveniently modified to investigate other experimental designs. In the presence of rescue dNTP, direct competition occurs between excision or extension of a mismatch. At concentrations of rescue dNTP sufficient to suppress the gel band intensity at the mismatch target site, nucleotide incorporation and misincorporation rates can be obtained from the ratios of gel band intensities 3' (downstream) and 5' (upstream) to the target site, measured as a function dNTP concentration for "wrong" and "right" dNTP substrates. The polymerase misincorporation efficiency, in the presence of proofreading, is given by the ratio of wrong to right incorporation efficiencies, Vmax/Km, obtained from the gel band ratios. The bacteriophage T4 polymerase with a highly active 3'-exonuclease activity was used to illustrate the assay. Nucleotide misincorporation efficiencies measured at several template sites were dCMP.A approximately equal to 10(-6), dGMP.A approximately equal to 10(-5), dTMP.T approximately equal to 2 x 10(-4), and dAMP.A < 10(-7). Proofreading of the dGMP.A mispair was suppressed by about 3-fold in the presence of high concentrations of next correct "rescue" dNTP causing a concomitant reduction in the fidelity of dGMP.A to about 3 x 10(-5).

Base Sequence↗