Biomedical subjects

C A Stevens

Publications and source records attributed to C A Stevens.

At least 19 recordsLinked to original sources

PubMed2003

The economic impact of preschool asthma and wheeze.

The aim of the present study was to determine the economic impact in the UK of wheezing disorders in preschool children. Health, societal and family-borne costs were calculated for a sample of 94 preschool children who attended hospital with a primary diagnosis of wheeze or asthma during 1998/1999. Sample costs were calculated using data from a structured interview schedule and from symptom diaries completed by trial parents, patients' general practice and hospital records, and hospital finance data. Health costs for 1-5-yr-olds in the UK were calculated using data from a postal population survey in the same region. It is estimated that 1-5-yr-old children with wheeze in the UK cost the health service a total of 53 million UK pounds (GBP). The greatest expenditure, 34 million GBP, was for primary care, representing 65.2% of total healthcare costs. Prescription costs represented 20.4% (11 million GBP) of total healthcare costs. Caring for preschool children with wheeze in the UK cost the health service 0.15% of its total budget in 1998/1999. The total costs to society of caring for the 0.88% of preschool children who attended hospital for asthma or wheeze in a year represented a further 2.6 million UK pounds. Primary prevention strategies at the population level promise more cost savings than any attempt at decreasing hospitalisations in those more severely ill.

Age Factors↗

PubMed2002

Parental education and guided self-management of asthma and wheezing in the pre-school child: a randomised controlled trial.

BACKGROUND: The effects on morbidity were examined of providing an educational intervention and a written guided self-management plan to the parents of pre-school children following a recent attendance at hospital for asthma or wheeze. METHODS: A prospective, randomised, partially blinded, controlled trial was designed at two secondary care centres. Over a 13 month period 200 children aged 18 months to 5 years at the time of admission to a children's ward or attendance at an accident and emergency department or children's (emergency) assessment unit (A&E/CAU) with a primary diagnosis of acute severe asthma or wheezing were recruited. 101 children were randomised into the control group and received usual care and 99 were assigned to the intervention group and received: (1) a pre-school asthma booklet; (2) a written guided self-management plan; and (3) two 20 minute structured educational sessions between a specialist respiratory nurse and the parent(s) and child. Subjects were assessed at 3, 6, and 12 months. The main outcomes were GP consultation rates, hospital re-admissions, and attendances at A&E/CAU. Secondary outcomes included disability score, caregivers' quality of life, and parental knowledge of asthma. RESULTS: There were no statistically significant differences between the two groups during the 12 month follow up period for any of the main or secondary outcome measures. CONCLUSIONS: These results do not support the hypothesis that the introduction of an educational package and a written guided self-management plan to the parents of pre-school children with asthma who had recently attended hospital for troublesome asthma or wheeze reduces morbidity over the subsequent 12 months.

Asthma↗

PubMed2001

Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta 4 integrin gene (ITGB4) and genotype/phenotype correlations.

Epidermolysis bullosa with pyloric atresia (EB-PA: OMIM 226730), also known as Carmi syndrome, is a rare autosomal recessive genodermatosis that manifests with neonatal mucocutaneous fragility associated with congenital pyloric atresia. The disease is frequently lethal within the first year, but nonlethal cases have been reported. Mutations in the genes encoding subunit polypeptides of the alpha 6 beta 4 integrin (ITGA6 and ITGB4) have been demonstrated in EB-PA patients. To extend the repertoire of mutations and to identify genotype-phenotype correlations, we examined seven new EB-PA families, four with lethal and three with nonlethal disease variants. DNA from patients was screened for mutations using heteroduplex analysis followed by nucleotide sequencing of PCR products spanning all beta 4 integrin-coding sequences. Mutation analysis disclosed 12 distinct mutations, 11 of them novel. Four mutations predicted a premature termination codon as a result of nonsense mutations or small out-of-frame insertions or deletions, whereas seven were missense mutations. This brings the total number of distinct ITGB4 mutations to 33. The mutation database indicates that premature termination codons are associated predominantly with the lethal EB-PA variants, whereas missense mutations are more prevalent in nonlethal forms. However, the consequences of the missense mutations are position dependent, and substitutions of highly conserved amino acids may have lethal consequences. In general, indirect immunofluorescence studies of affected skin revealed negative staining for beta 4 integrin in lethal cases and positive, but attenuated, staining in nonlethal cases and correlated with clinical phenotype. The data on specific mutations in EB-PA patients allows prenatal testing and preimplantation genetic diagnosis in families at risk.

Amino Acid Sequence↗

PubMed1999

Tibial hemimelia in Langer-Giedion syndrome-possible gene location for tibial hemimelia at 8q.

We report on a girl with Langer-Giedion syndrome or tricho-rhino-phalangeal syndrome, type II (TRPS II) with deletion on 8q, and the unusual findings of bilateral tibial hemimelia and unilateral absence of the ulna. An 8-year-old boy with TRPS II with bilateral tibial hemimelia was reported by Turleau et al. [1982: Hum. Genet. 62:183-187]. The critical region for TRPS II is 8q24.1. Although no genes involving limb development in the human have been identified in this region, two mouse syndromes are localized to the homologous chromosome region of 9A1-A4 which involve limb abnormalities. We propose that a gene involved in limb development is contiguous with the TRPS II gene which, when deleted, may cause tibial hemimelia.

Arm↗

PubMed1997

Patellar dislocation in Rubenstein-Taybi syndrome.

This report describes 11 patients with Rubinstein-Taybi syndrome (RTS) and patellar dislocation. The age at diagnosis of patellar dislocation ranged from birth to 16 years. Ten patients had chronic dislocations and 8 of 11 had bilateral patellar dislocations. Eight patients required surgical stabilization of the patella; most achieved a good outcome with surgical repair. All families reported that the patellar dislocations impaired developmental skills which improved after surgery. Seven of the 11 patients were described as having other joint abnormalities including congenital dislocations and laxity of the joints. Patients with RTS should undergo regular thorough joint examinations, including the knees, because abnormalities may result in delay of attainment of motor skills.

Adult↗

PubMed1997

Macrocephaly-cutis marmorata telangiectatica congenita: a distinct disorder with developmental delay and connective tissue abnormalities.

We describe 13 unrelated children with abnormalities of somatic growth, face, brain, and connective tissue including vasculature. Although the condition in these children falls under the general group of disorders known as cutis marmorata telangiectatica congenita (CMTC), the constellation of abnormalities appears to constitute a distinct and easily recognizable phenotype within this general group. In contrast to most children reported with CMTC, children in this subgroup have a high risk for neurologic abnormalities, including developmental delay, mental retardation, megalencephaly, and hydrocephalus. Early recognition of this condition is important for appropriate surveillance for known complications and parental counseling.

Abnormalities, Multiple↗

PubMed1996

Over-utilization of the J delta 3 gene-segment in Crohn's disease.

A majority of normal human intestinal intraepithelial lymphocytes (iIEL) are CD8+, express the alpha beta-T cell receptor (TCR) and are oligoclonal. The remainder of normal iIELs, which are also oligoclonal, express the gamma delta-TCR and preferentially utilize variable regions (V delta 1 and V delta 3) which are different from adult peripheral blood lymphocytes (V delta 2). The junctional region usage of gamma delta-TCRs in intestinal diseases is largely unknown. The aim of this study was to examine gamma delta-T cell clonality and junctional region usage of V delta 1 and V delta 3 transcripts in Crohn's Disease (CD) in comparison to several other chronic inflammatory diseases of the colon by polymerase chain reaction amplification, cloning and sequencing. As previously observed in normal subjects, all inflammatory cases examined, including CD (n = 3), ulcerative colitis (n = 1), diverticulitis (n = 1) and lymphocytic colitis (n = 1), the V delta 1 and V delta 3 transcripts contained reiterated sequences consistent with the expansion of gamma delta-T cells expressing these receptors. In 2/3 CD cases, but none of the non-CD inflammatory cases, transcripts containing J delta 3, a rarely used J delta, was observed among the V delta 1 and/or V delta 3 transcripts. Thus, in a subset of CD, gamma delta-T cells expressing J delta 3 may be expanded implicating a role for unique ligands that drive the expansion of T cells expressing these receptors.

Amino Acid Sequence↗

PubMed1996

Major-locus contributions to variability of the craniofacial feature dystopia canthorum in Waardenburg syndrome.

We used segregation analysis to investigate the genetic basis of variation in dystopia canthorum, one of the key diagnostic features of Waardenburg syndrome type 1 (WS1). We sought to determine whether the W-index, a quantitative measure of this craniofacial feature, is influenced primarily either by allelic variation in the PAX3 disease gene or other major loci, by polygenic background effects, or by all of these potential sources of genetic variation. We studied both WS1-affected individuals and their WS1-unaffected relatives. After adjustment of the W-index for WS1 disease status, segregation analyses by the regression approach indicated major-locus control of this variation, although residual parent-offspring and sib-sib correlations are consistent with additional (possibly polygenic) effects. Separate analyses of WS1-affected and WS1-unaffected individuals suggest that epistatic interactions between disease alleles at the PAX3 WS1 locus and a second major locus influence variation in dystopia canthorum. Our approach should be applicable for assessing the genetic architecture of variation associated with other genetic diseases.

Alleles↗

PubMed1995

Cardiac abnormalities in the Rubinstein-Taybi syndrome.

In order to evaluate the incidence of cardiac anomalies, type of cardiac defects, and their impact in the Rubinstein-Taybi syndrome (RTS), a questionnaire study was done. Forty-five of 138 patients in the study (32.6%) had a known cardiac abnormality; 27 patients had single defects including atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA), coarctation of the aorta, pulmonic stenosis, or bicuspid aortic valve. Eight of these individuals had spontaneous resolution of their problems, while 8 required surgery. Sixteen patients had complex congenital heart defects or two or more abnormalities. Two patients had spontaneous resolution, while 7 required surgery. Surgery is planned in 5 additional patients. Five patients had conduction abnormalities. Individuals with congenital heart defects did not have a higher incidence of other birth defects. The significant incidence and potential severity of cardiac anomalies in our patients suggest that a cardiac evaluation should be strongly considered in patients with RTS.

Adolescent↗

PubMed1995

Analysis of variability of clinical manifestations in Waardenburg syndrome.

Expression of clinical findings of Waardenburg syndrome type 1 (WS1) and type 2 (WS2) is extremely variable. Using our collection of 26 WS1 and 8 WS2 families, we analyzed the occurrence, severity, and symmetry of clinical manifestations associated with WS. We found significant differences between WS1 and WS2 in deafness, and in pigmentary and craniofacial anomalies. Factor analysis was used to identify manifestations which covaried, resulting in 2 orthogonal factors. Since mean factor scores were found to differ when compared between WS1 and WS2, we suggest that these factors could be useful in distinguishing WS types. We found that the WS gene was transmitted from mothers more often than from fathers. We also extensively examined the W-Index, a continuous measure of dystopia canthorum. Our data suggest that use of the W-Index to discriminate between affected WS1 and WS2 individuals may be problematic since 1) ranges of W-Index scores of affected and unaffected individuals overlapped considerably within both WS1 and WS2, and 2) a considerable number of both affected and unaffected WS2 individuals exhibited W-index scores consistent with dystopia canthorum. Misclassification of families may have implications for risk assessment of deafness, since WS2 families have been reported to have greater incidence of deafness, as confirmed in our study.

Age Factors↗

PubMed1995

Syndromal frontonasal dysostosis in a child with a complex translocation involving chromosomes 3, 7, and 11.

We report on a 4-year-old boy with typical frontonasal dysostosis and an apparently balanced de novo translocation involving chromosomes 3, 7, and 11, and four breakpoints. The karyotype was 46,XY,t(7;3)(3;11) (7pter-->7q21.3::3q27-->3qter;3pter-->3 q23::11q21-->11qter; 11pter-->11q21::3q23-->3q27::7q21.3-->7 qter). In situ hybridization with a chromosome 3 painting probe confirmed the interpretation from GTG banding. The child had a widow's peak, marked hypertelorism, absence of the nasal tip, and widely separated nares. He also had an atrial septal defect, micropenis, small testes, clubfeet, scoliosis, block C2-4, and structural brain abnormalities on MRI. In review we found two other cases of frontonasal dysostosis with chromosome abnormalities, neither of which was similar to our case. The presence of a de novo (apparently) balanced translocation in our patient may help to locate the gene(s) for frontonasal dysplasia and perhaps other midline craniofacial malformations.

Abnormalities, Multiple↗

PubMed1994

Pulmonary hyperplasia in the Fraser cryptophthalmos syndrome.

We report on 2 sibs with the Fraser cryptophthalmos syndrome who had pulmonary hyperplasia and laryngeal stenosis. A third unrelated patient with Fraser syndrome had laryngeal stenosis, renal agenesis, and normal lung development, rather than the expected pulmonary hypoplasia. Three additional cases of pulmonary hyperplasia in the Fraser syndrome were ascertained from a review. In all of these cases the likely mechanism for pulmonary hyperplasia is retention of fetal lung fluid by laryngeal or tracheal obstruction.

Abnormalities, Multiple↗

PubMed1994

Mental retardation and Ullrich-Turner syndrome in cases with 45,X/46X,+mar: additional support for the loss of the X-inactivation center hypothesis.

Four cases having mosaicism for a small marker or ring [45,X/46,X,+mar or 45,X/46,X,+r] chromosome were ascertained following cytogenetic studies requested because of minor anomalies (cases 1, 3, and 4) and/or short stature (cases 2 and 4). While all 4 cases had traits typical of Ullrich-Turner syndrome (UTS), cases 1, 3, and 4 had manifestations not usually present in UTS, including unusual facial appearance, mental retardation/developmental delay (MR/DD) (cases 3 and 4), and syndactylies (case 1). The facial appearances of cases 1 and 3 were similar yet distinct from that of case 4. Using fluorescence in situ hybridization (FISH), each of the markers in these 4 cases was identified as having been derived from an X chromosome. The level of mosaicism for the mar/r(X) cell line in these cases varied from 70% (case 1) to 16% (case 4) but was not apparently correlated with the presence of MR/DD. Replication studies demonstrated a probable early replication pattern for the mar/r(X) in cases 1, 3, and 4, while the marker in case 2 was apparently late replicating. To date, 41 individuals having mosaicism for a small mar/r(X) chromosome have been described. Interestingly, most of the 14 individuals having a presumedly active mar/r(X) demonstrated clinical findings atypical of UTS, including abnormal facial changes (11) and MR/DD (13). MR was noted most frequently in those cases having at least 50% mosaicism for the marker or ring. In contrast, atypical UTS facial appearance or MR/DD was not noted in 14 of the 16 cases with UTS who carried a probable late replicating marker or ring. In conclusion, although the phenotype of 45,X/46,X,mar/r(X) individuals appears to be influenced by the genetic content and degree of mosaicism for the mar/r(X), the most significant factor associated with MR/DD appears to be the activity status of the mar/r(X) chromosome. Thus, our 4 cases provide further support for the hypothesis that a lack of inactivation of a small mar/r(X) chromosome may be a factor leading to the MR and other phenotypic abnormalities seen in this subset of individuals having atypical UTS.

Child↗

PubMed1994

Management of death, dying and euthanasia: attitudes and practices of medical practitioners in South Australia.

This article presents the first results of a study of the decisions made by health professionals in South Australia concerning the management of death, dying, and euthanasia, and focuses on the findings concerning the attitudes and practices of medical practitioners. Mail-back, self-administered questionnaires were posted in August 1991 to a ten per cent sample of 494 medical practitioners in South Australia randomly selected from the list published by the Medical Board of South Australia. A total response rate of 68 per cent was obtained, 60 per cent of which (298) were usable returns. It was found that forty-seven per cent had received requests from patients to hasten their deaths. Nineteen per cent had taken active steps which had brought about the death of a patient. Sixty-eight per cent thought that guidelines for withholding and withdrawal of treatment should be established. Forty-five per cent were in favour of legalisation of active euthanasia under certain circumstances.

Adult↗

PubMed1994

Nurses and the management of death, dying and euthanasia.

This article is one of two which report findings of research which examined the attitudes and practices of health professionals in South Australia towards the management of death, dying and euthanasia. The focus in this article is on findings related to nurses. Conducted in August 1991, mail-back, self-administered questionnaires were posted to a sample of 500 nurses on the general nurses register held by the Nurses Board of South Australia. A total response rate of 57.8% was obtained, and 55% (278) were usable returns. The survey found that 47% of the respondents had received requests from patients to hasten their deaths by withdrawing treatment, and 30% had received request from patients for active euthanasia. 'Persistent and irrelievable pain' was the main reason for such requests. The majority either would or did discuss such requests with relatives, other medical practitioners and nursing staff. Nineteen per cent had taken active steps which had brought about the death of a patient. Eighty-two per cent thought that guidelines for withholding and withdrawal of treatment should be established. Sixty per cent were in favour of legalization of active euthanasia under certain circumstances.

Adult↗

PubMed1993

Malformations and deformations in abdominal pregnancy.

Abdominal gestation is a relatively uncommon complication of pregnancy. Previous reports describe a high incidence of fetal deformations and mortality as well as maternal mortality. A case of twin abdominal gestation is presented and the literature concerning abdominal pregnancy since 1809 is reviewed. The survival rate of liveborn infants of 30 or more weeks gestation was 63%. The maternal mortality rate since 1809 was 18.2%, but this has decreased to 4.5% during the last 20 years. The combined rate of malformations and deformations in the infants was 21.4%. The most common deformations observed were facial and/or cranial asymmetry and various joint abnormalities. Among the most common malformations were limb deficiency and central nervous system malformations. Proposed mechanisms of compression and vascular disruption are discussed.

Female↗

PubMed1993

Two sibs with different phenotypes due to adjacent-1 segregation of a subtle translocation t(4;5)(p16.3;p15.3)mat.

High-resolution chromosome banding and in situ hybridization with combined cosmid and alphoid sequence probes were used to delineate a very small reciprocal translocation in a mother and her two children. The first child has a 46,XX,der(4)t(4;5)(p16.3;p15.3)mat and thus has a deletion of 4p16.3-->pter and a duplication of 5p15.3-->pter (most likely 5p15.31-->pter). Clinical findings include marked growth retardation, developmental delay, seizure disorder, microcephaly, unruly hair, broad nasal tip, downturned mouth, narrow palate, 11 pairs of ribs, mild right club foot, and a deep sacral dimple. Thus, this child has only a few non-specific manifestations of Wolf-Hirschhorn syndrome. The second child has a 46,XY,der(5)t(4;5)(p16.3;p15.3)mat; thus a deletion of 5p15.3-->pter and a duplication of 4p16.3-->pter. He has failure to thrive, developmental delay, microcephaly, sparse hair, horizontal nystagmus, short upturned nose with flared nostrils, thin lips with overhanging upper lip, long fingers and toes, and hypertonicity. Findings in the second patient are not suggestive of cri du chat syndrome (del 5p). The mother is phenotypically normal. This translocation will be useful in mapping genes and markers on the 4p and 5p chromosomal regions.

Abnormalities, Multiple↗

PubMed1993

Increased airway inflammation with segmental versus aerosol antigen challenge.

Airway inflammation is increasingly recognized as a pivotal component of asthma. Because allergens provoke bronchial constriction and inflammation in allergic subjects, bronchial antigen challenge has emerged as a powerful technique for evaluating mechanisms involved in this process. In this study, we compare whole lung antigen challenge (WLAC) with segmental bronchoprovocation (SBP) in eight allergic, non-asthmatic, non-smoking subjects, and evaluated the response by bronchoalveolar lavage (BAL) prior to, and 48 h after antigen challenge. Both challenge techniques evoked airway inflammation, manifest as an increase in total cells and eosinophils recovered by BAL, an increase in total protein concentration, and enhanced production of superoxide anion by airspace cells. The degree to which these changes occurred was significantly greater with SBP than WLAC, and only SBP evoked persistent measurable change in alveolar macrophage density and eosinophil granule protein concentrations. Moreover, although both techniques were associated with a comparable immediate fall in FEV1, only WLAC resulted in statistically significant persistent physiologic changes 48 h afterwards. We conclude that, as anticipated, SBP produces more intense airway inflammation in allergic subjects, does not result in late airway obstruction, and offers specific advantages in studying allergen-driven airway inflammation.

Adult↗