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Biomedical subjects

A Child

Publications and source records attributed to A Child.

At least 37 records · Page 2Linked to original sources
PubMed1996

Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region.

Primary open angle glaucoma (GLC1) is a common ocular disorder with a characteristic degeneration of the optic nerve and visual field defects that is often associated with an elevated intraocular pressure. The severe but rare juvenile-onset type has previously been mapped to 1q21-q31, and its genetic heterogeneity has been established. Herein, we present a new locus (GLC1B) for one form of GLC1 on chromosome 2cen-q13 with a clinical presentation of low to moderate intraocular pressure, onset in late 40s, and a good response to medical treatment. Two-point and haplotype analyses of affected and unaffected meioses in six families provided maximum linkage information with D2S417, GATA112EO3, D2S113, D2S373, and D2S274 (lod scores ranging from 3.11 to 6.48) within a region of 8.5 cM that is flanked by D2S2161 and D2S2264. Analysis of affected meioses alone revealed no recombination with an additional two markers (D2S2264 and D2S135) in a region of 11.2 cM that is flanked by D2S2161 and D2S176. Analysis of unaffected meioses identified only one healthy 86-year-old male who has inherited the entire affected haplotype and, hence, is a gene carrier for this condition. Eight additional families with similar and/or different clinical presentation did not show any linkage to this region and, therefore, provided evidence for genetic heterogeneity of adult-onset primary open angle glaucoma.

Age of Onset↗
PubMed1996

Pregnancy outcomes in urban aboriginal women.

OBJECTIVE: To assess Aboriginal women's access to antenatal care and their pregnancy outcomes in an urban setting. DESIGN: Retrospective descriptive study using an obstetric database. SETTING: King George V Memorial Hospital, Sydney. PATIENTS: All women who gave birth between 1 January 1992 and 31 December 1993. OUTCOME MEASURES: Age and parity, gestation at first antenatal visit and at delivery, antenatal complications, type of delivery, infant birthweights and perinatal mortality were compared between Aboriginal and non-Aboriginal women. Within the Aboriginal group, comparisons were made between those with and without poor pregnancy outcomes (low birthweight infants and perinatal deaths). RESULTS: Aboriginal women were younger and of higher parity than non-Aboriginal women and booked for confinement later in pregnancy, although nearly 80% were booked by 28 weeks' gestation. There was more pregnancy-induced hypertension (P < 0.01; relative risk [RR], 1.66; 95% confidence interval [Cl], 1.17-2.37), urinary tract infection (P < 0.02; RR, 2.45; 95% Cl, 1.27-4.30) and need for methadone stabilisation in Aboriginal women (P < 0.001; RR, 5.88; 95% Cl, 2.99-11.57). In the Aboriginal group, there were higher preterm delivery rates (P < 0.001; 95% Cl, 1.31-2.74), more low birthweight babies (P < 0.001; 95% Cl, 1.67-3.33) and higher perinatal mortality rates. These findings applied to both Aboriginal women transferred from metropolitan district and country hospitals and those resident in central Sydney. Factors associated with low birthweight and perinatal deaths in Aboriginal infants included late antenatal booking, cigarette smoking, hypertension and urinary tract infection in pregnancy, and antepartum haemorrhage. CONCLUSION: Further efforts must be made to improve access of Aboriginal women to antenatal services in the Central Sydney Area to improve perinatal outcomes and maternal health.

Adult↗
PubMed1996

Genetic analysis of structural elastic fiber and collagen genes in familial adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis is a genetic disorder of unknown etiology. Scoliosis is a clinical feature of inherited connective-tissue disorders including Marfan syndrome. Mutations within the gene of FBN1 (fibrillin 15), a component of the extracellular matrix, are now linked to Marfan syndrome and similar clinical phenotypes. This study investigated the potential association of structural genes encoding for extracellular matrix components of FBN1, elastin, and one of the polypeptides of type-I collagen (COL1A2) with familial adolescent idiopathic scoliosis. Eleven pedigrees, including 96 individuals, were identified in which adolescent idiopathic scoliosis segregated in an apparent autosomal dominant pattern. Fifty-two individuals were determined to be affected with scoliosis. Genomic DNA was analyzed by genetic linkage utilizing four intragenic markers for the structural genes of FBN1, elastin, and COL1A2. Collectively, our results exclude the structural genes of FBN1, elastin, and COL1A2 as candidate genes within these families. However, when viewed individually, specific markers cannot be excluded within all of the families. This information complements previously reported data that fibrillin production and matrix incorporation from scoliotic fibroblasts in vitro are normal in more than 80% of patients studied.

Adolescent↗
PubMed1996

Is the metacarpal index useful in the diagnosis of Marfan syndrome?

AIM: This study was undertaken to analyse the importance of the Metacarpal Index (MCI) in making the diagnosis of Marfan syndrome. PATIENTS AND METHODS: The characteristics of 42 patients with Marfan syndrome as defined by strict criteria were analysed. Fifty-one consecutive accident and emergency patients comprised the control group for the MCI measurements. RESULTS: Using MCI alone four (7.8%) of controls had an abnormal MCI, and seven (16.6%) of Marfan patients were normal. Thirty-two (76%) of Marfan patients had an abnormal MCI and three (13.4%) were equivocal. Using other skeletal parameters (upper segment to lower segment ratio, arm span 3 cm or more greater than height, or palate, pectus or scoliosis deformity) 40 (95%) of the Marfan group had an abnormality. Other parameters: 18 (43%) in the Marfan group gave a history of retinal detachment or ectopia lentis. Echocardiographic measurements showed aortic root dilatation in 29 (69%) and in 21 (50%) mitral valve prolapse was found; 37 (88%) had one or other cardiac abnormality. Using all parameters excluding MCI: All the patients would still have fulfilled the diagnostic criteria for the diagnosis of Marfan syndrome. CONCLUSION: The role of the MCI, a radiation dependent and time consuming measurement, is probably insignificant in diagnosis of the majority of Marfan patients. Combined with clinical measurements, an echocardiogram is probably the single most useful investigation, aiding both diagnosis and management.

Adult↗
PubMed1996

Extra-articular features of benign joint hypermobility syndrome.

To define the phenotype of patients with benign joint hypermobility syndrome (BJHS), we studied 58 consecutive patients (mean age 37 yr) presenting to a rheumatology clinic and 30 controls. Patients underwent rheumatological and ophthalmic examination, hypermobility scoring, echocardiography, measurement of bone mineral density (BMD), and skin thickness, elasticity and light transmissibility. The median hypermobility score was 5/9 Beighton and 31/56 Contompasis. Eighteen (31%) patients complained of significant arthralgia. Six (10%) patients and two (7%) controls had mitral valve prolapse (MVP) (chi(2) = 0.27, P = NS). Neither MVP nor aortic diameters showed a correlation with hypermobility score. There was no significant reduction in BMD. There was a significant correlation between hypermobility and light transmissibility of the skin (r = 0.71, P < 0.0001 Contompasis; r = 0.47, P < 0.05 Beighton) and skin stretchiness (r = 0.49, P < 0.05 Contompasis; r = 0.39, P < 0.05 Beighton). On ophthalmic examination, 14 (41%) patients had upper eyelid laxity. Thus, patients with BJHS do not have an increased prevalence of significant cardiac, bone, skin or eye abnormalities, helping differentiate BJHS from other more serious hereditary disorders of connective tissue.

Adolescent↗
PubMed1995

Prenatal diagnosis of Marfan syndrome: identification of a fibrillin-1 mutation in chorionic villus sample.

Marfan syndrome (MFS) is one of the most common heritable connective tissue disorders and is caused by mutations in a gene coding for fibrillin-1. All but one of over 30 published mutations have been unique and specific prenatal diagnostics can only be provided to families with a previously established mutation. We have earlier identified a 366 bp deletion of fibrillin mRNA in a three-generation British Marfan family. An affected female in the family together with her husband sought prenatal diagnosis. Chorionic villus sampling was performed at 11.5 weeks of gestation and total RNA was directly extracted from the sample. After reverse transcription and polymerase chain reaction (PCR) of the cDNA, the same deletion was identified in the chorionic villus sample (CVS) and the mother's sample in agarose gel electrophoresis. The fetal origin of the CVS was confirmed with polymorphic markers. In addition to the mutation analysis, CVS cells of the proband and a control fetus were cultured for biochemical studies of fibrillin polypeptides. The results of the biochemical investigation were in concordance with the molecular analysis.

Adult↗
PubMed1995

As good as anyone: antenatal shared care at an inner Sydney hospital.

An exploratory survey design was used to assess satisfaction with antenatal care over a two-month period of women giving birth in an inner Sydney teaching hospital. Patients received obstetric services from private obstetricians, midwives, the hospital outpatient clinic, or 'shared care' between general practitioners and the outpatient clinic or birth centre. Insurance status and demographic information were collected across all groups. Shared care patients gave reasons why they chose that model of antenatal service. Ten per cent of women in the sample received shared care. Shared care patients were equally as satisfied as those in other modes of care in all but one factor--promptness of service (in which private obstetricians received higher ratings). They also judged shared care to have the advantages of being convenient, personal, and culturally appropriate. Significantly more patients in the shared care group were born overseas and they were less likely to hold private insurance. This paper discusses the results of the current study in the context of the Australian literature, explores some issues surrounding satisfaction research, and suggests further research arising from this work.

Australia↗
PubMed1994

Analyses of truncated fibrillin caused by a 366 bp deletion in the FBN1 gene resulting in Marfan syndrome.

We studied fibrillin synthesis in cultured fibroblasts from 11 members of a three-generation family with Marfan syndrome, caused by a large in-frame deletion in FBN1 (the fibrillin gene) leading to a loss of 366 bases in the corresponding fibrillin mRNA. Metabolic labelling with [35S]Met/Cys and SDS/PAGE allowed unequivocal identification of normal and truncated fibrillin in all cell strains harbouring the deletion. In culture medium, fibrillin and its truncated counterpart were predominant, whereas their respective larger precursors were found only in traces. This proportion, however, was markedly shifted towards the normal and truncated precursors by EGTA and reversed by the addition of calcium, which confirmed the existence of profibrillin and its probably calcium-dependent conversion into fibrillin. Tunicamycin caused increased electrophoretic mobility of normal and truncated molecules without changing their apparent size differences. Intracellularly, only profibrillin was found; in the mutant cells truncated and normal profibrillin molecules were present in similar amounts and both populations were secreted and deposited simultaneously into the extracellular matrix; there, however, truncated profibrillin only became easily detectable after treatment of cells with dextran sulphate, which increased the amount of extractable profibrillin. Immunofluorescence microscopy in patients' cultures identified fibrillin-containing microfibrils which appeared to be moderately reduced both in amount and diameter. Ultrastructural analysis by rotary-shadowing and immunogold electron microscopy demonstrated the presence of numerous beaded domains reacting with fibrillin antibodies, but no intact fibrillin microfibrils in patient's cell-layer extracts, in contrast with the extensive microfibrils elaborated by control cultures. Our findings suggest, that in the patients' cell cultures all microfibrils contained the truncated fibrillin molecules.

Actin Cytoskeleton↗
PubMed1994

A novel mutation of the fibrillin gene causing ectopia lentis.

Ectopia lentis (EL), a dominantly inherited connective tissue disorder, has been genetically linked to the fibrillin gene on chromosome 15 (FBN1) in earlier studies. Here, we report the first EL mutation in the FBN1 gene confirming that EL is caused by mutations of this gene. So far, several mutations in the FBN1 gene have been reported in patients with Marfan syndrome (MFS). EL and MFS are clinically related but distinct conditions with typical manifestations in the ocular and skeletal systems, the fundamental difference between them being the absence of cardiovascular involvement in EL. We report a point mutation, cosegregating with the disease in the described family, that displays EL over four generations. The mutation changes a conserved glutamic acid residue in an EGF-like motif, which is the major structural component of the fibrillin and is repeated throughout the polypeptide. In vitro mutagenetic studies have demonstrated the necessity of an analogous glutamic acid residue for calcium binding in an EGF-like repeat of human factor IX. This provides a possible explanation for the role of this mutation in the disease pathogenesis.

Amino Acid Sequence↗
PubMed1994

Differential allelic expression of a fibrillin gene (FBN1) in patients with Marfan syndrome.

Marfan syndrome is a connective-tissue disorder affecting cardiovascular, skeletal, and ocular systems. The major Marfan locus has been identified as the FBN1 gene on chromosome 15; this codes for the extracellular-matrix protein fibrillin, a 350-kD constituent of the 8-10-nm elastin-associated microfibrils. We identified five MFS patients who were heterozygous for an RsaI restriction-site dimorphism in the 3' UTR of the FBN1 gene. This expressed variation was used to distinguish the mRNA output from each of the two FBN1 alleles in fibroblast cultures from these five patients. Three of the patients were shown to produce < 5% of the normal level of FBN1 transcripts from one of their alleles. This null-allele phenotype was not observed in 10 nonmarfanoid fibroblast cell lines.

Adult↗
PubMed1994

Unrecognized dyslipoproteinemia in United Kingdom families recruited to a genetic register because of unexplained coronary heart disease.

A register was built up of DNA from United Kingdom families with premature coronary heart disease and no perceived risk associations in the expectation that obscure causal factors could be defined through future genetic analysis. Referrals came from interested, predominantly cardiologic units in southern England. For inclusion, probands had documented coronary heart disease before age 55 years that was regarded as unexplained, in families with at least two living affected first-degree and two other members, in most families over two generations. Referred probands and family members completed a questionnaire on general health and habits and were examined for body mass index, blood pressure, resting electrocardiogram, and lipoprotein profile. Data are presented on 276 living members from 26 families, representing 75.4% of all members age 15 years and older. The striking observation was the extent of dyslipoproteinemia that was not identified by the referring units as relevant to the expression of accelerated coronary heart disease. This was expressed as hypercholesterolemia, reduced levels of high-density lipoprotein, or both, in comparison with profiles recorded over the same period and for a similar but unselected general British population. Further genetic analysis for a major occult risk factor in these families is inappropriate. Present concerns with potential adverse associations with low cholesterol, or with lipid-lowering treatment, should be addressed in the knowledge that uncontrolled dyslipoproteinemia also has severe adverse associations. These associations are still not widely appreciated in the management of patients and families with premature coronary heart disease.

Adult↗
PubMed1992

Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides.

Biochemical and molecular genetic studies have recently suggested that mutations in the gene coding for fibrillin on chromosome 15 result in Marfan syndrome. To our knowledge, only one mutation in the fibrillin gene has been published. Here we report the results of screening 20 unrelated MFS patients for mutations in fibrillin cDNA by the single-strand conformation polymorphism technique. We found two mutations, both of which appear in the heterozygote form and code for a shortened fibrillin polypeptide. The first mutation is a large in-frame deletion of 366 bases of the fibrillin mRNA, shown to result in a truncated but secreted polypeptide found in the fibroblast culture of the patient. The second mutation is a G-to-A transition resulting in the substitution of a stop codon for a tryptophan codon and thus predicting the premature termination of the polypeptide chain. We screened 60 other, unrelated MFS patients for these mutations as well as for the previously reported mutation (arginine-239 to proline) and found none of the three mutations in any of these patients. These data suggest that most MFS families carry their own distinct mutation.

Base Sequence↗
PubMed1992

Sources and types of referral to a haematology department.

An audit was undertaken of the case notes of all new outpatients referred to the haematology department at the Leeds General Infirmary over a one-year period. The source, reason for referral, final diagnosis and outcome were determined in each case, along with essential biographical details. The results show that general practitioners initiated over half of all referrals, often prompted by written comments from a hematologist on a full blood count advising them that further tests were required. Almost a third came from other departments at the study hospital and the remainder originated from hospitals outside the district. Most general practitioner referrals were made with a request for a diagnosis. Hospital initiated referrals were more likely to have a final diagnosis of a malignant haematological disease, whereas those from general practice tended to have benign or self-limiting conditions. Ninety-one per cent of patients referred had an abnormality. There were low numbers of both clinic defaulters and those patients required to be re-referred to other specialties. These results suggest that the high quality of referrals is largely due to the general practitioner's decision to refer patients based on the full blood count result. This often occurs after discussion with haematology medical staff. The possible impact of the government's White Paper proposals on this outpatient service is discussed.

Adolescent↗
PubMed1991

Marfan syndrome: no evidence for heterogeneity in different populations, and more precise mapping of the gene.

Marfan syndrome is a dominantly inherited connective tissue disorder with manifestations in the cardiovascular, ocular, and skeletal systems. The diagnosis is hampered by both high variability in the phenotypic expression and late manifestation of symptoms. The cause of Marfan syndrome remains unknown, but our group has recently reported the genetic linkage of Marfan syndrome to a polymorphic marker on chromosome 15. To analyze the possible heterogeneity behind Marfan syndrome, we have performed linkage analyses for four chromosome 15 markers in 17 families from five different populations: Scottish, English, Swiss, American, and Finnish. By combining the linkage data of all the studied families into a LINKMAP analysis we obtained a maximal LOD score of 11.2, which maps the Marfan syndrome locus between D15S25 and D15S45 on the long arm of chromosome 15. The data reveal no evidence for genetic heterogeneity behind Marfan syndrome and provide us with a more precise location of both the Marfan syndrome locus and flanking markers. This information will provide the basis for the DNA diagnostics of Marfan syndrome in the future.

Chromosome Mapping↗
PubMed1990

Recovery after childbirth: a preliminary prospective study.

This prospective study examined the time for 93 women to cease to feel discomfort in their perineal areas after the births of their first babies. Sixty-two of the women had experienced a spontaneous delivery that did not require forceps assistance. In 58 patients, an episiotomy was performed. Of the 35 women in whom an episiotomy was not performed, 24 women required sutures and only four women did not suffer any perineal damage. The median time for perineal comfort in general (including walking and sitting) was one month (range, zero to six months); 20% of women took more than two months to achieve general perineal comfort. For comfort during sexual intercourse, the median time was three months (range, one to more than 12 months); 20% of women took longer than six months to achieve comfort during sexual intercourse. Factors that were associated with discomfort for longer than the median time were delivery by forceps; spontaneous vaginal (not perineal) tears; and, in the three to four days after the birth, oedema and the breakdown of muscle or skin sutures. There was no significant difference in these times between patients who did not undergo an episiotomy and those who underwent an episiotomy without a forceps delivery.

Adolescent↗