Biomedical subjects

Stephen Robertson

Publications and source records attributed to Stephen Robertson.

5 recordsLinked to original sources

PubMed2006

Effect of calcium tablets on interpretation of lumbar spine DXA scans.

Undissolved calcium (Ca) tablets in the gastrointestinal tract at the time of a dual-energy X-ray absorptiometry (DXA) scan could conceivably affect the accuracy of the lumbar spine bone mineral density (BMD) determination. We studied phantoms and volunteers to determine the effect of Ca tablets overlying bone, Ca tablets in the soft-tissue field, and Ca tablets overlapping both bone and soft tissue. For L1-4, a 500-mg Ca tablet taped to the phantom surface or the skin of volunteers resulted in <or=2.2% mean increase in measured BMD (less than the lumbar spine least significant change), changing the T-score for L1-4 very little. However, an overlying Ca tablet had a substantial effect on BMD of a single vertebral body. Greater effects were seen with higher amounts of tablet Ca and with lower BMD, resulting in as much as a 12.6% mean increase in single vertebral BMD in the in vivo series. Recent versions of DXA software successfully identified tablets in the soft-tissue field as artifact and eliminated the tablet pixels from the analysis. However, tablets overlapping bone and soft tissue necessitated operator intervention to either exclude the affected vertebral body or adjust edges by mapping the tablet as artifact and/or neutral field. A paraffin-coated Ca tablet swallowed by a volunteer was tracked serially by DXA during gastrointestinal transit. Similar effects were seen as with the phantom and volunteer studies using external tablets; there was little effect of the Ca tablet on L1-4 BMD either with the tablet overlying bone or in the soft-tissue field. We conclude that undissolved Ca tablets introduce small artifacts on L1-L4 BMD insufficient to alter diagnostic categorization of patients. However, if only two or three vertebral levels are available, misclassification of the patients may occur due to tablet artifact. The precision of monitoring BMD over time could also be adversely affected by tablet artifact if a tablet was directly overlying bone and undetected, especially with smaller regions of interest and with lower baseline BMD.

Absorptiometry, Photon↗

PubMed2006

Functional copper transport explains neurologic sparing in occipital horn syndrome.

OBJECTIVE: A range of neurologic morbidity characterizes childhood-onset copper transport defects, including severe Menkes disease and milder occipital horn syndrome. Both phenotypes are caused by mutations in ATP7A, which encodes a copper-transporting adenosine triphosphatase, although defects causing occipital horn syndrome are rarely reported and nearly always involve exon-skipping (six of eight prior reports). Our objective was to characterize a novel occipital horn syndrome mutation (N1304S) not associated with aberrant splicing and to determine whether functional copper transport was associated with this allele. METHODS: We studied two brothers with typical occipital horn syndrome and used yeast complementation and timed growth assays, exploiting a Saccharomyces cerevisiae mutant strain, to assess in vitro N1304S copper transport. RESULTS: We documented that N1304S has approximately 33% residual copper transport, a result not inconsistent with a similar patient we reported with an exon-skipping mutation whose cells showed correctly spliced mRNA transcripts 36% of normal. CONCLUSION: These patients' mild neurologic phenotypes, together with our yeast complementation and growth experiments, imply that N1304S does not completely block copper transport to the developing brain early in life. The findings suggest that neurologic sparing in untreated occipital horn syndrome is associated with approximately 30% residual functional activity of ATP7A.

Adenosine Triphosphatases↗

PubMed2005

Gracile bones, periostal appositions, hypomineralization of the cranial vault, and mental retardation in brothers: milder variant of osteocraniostenosis or new syndrome?

We report on two brothers with ossification anomalies of membranous and cranial bones, remodeling defect of long bones leading to dense, overtubulated, narrow diaphyses, metaphyseal flare, periostal hyperosotosis that increased during the first months of life, thoracic dystrophy and severe hypotonia. One boy had hypospadias and cleft palate. Follow-up of the surviving boy documented progressive osteopenia, slow healing of the periostal anomalies, liver angiomatosis, mental and motor delay, thoracic deformity, delay in tooth eruption, and progressive microcephaly with enlargement of the cerebral ventricles. This disorder shares some traits with osteocraniostenosis, but lacks the cranial deformity and acromelic micromelia of the latter, in which periostal anomalies are not described. The syndrome reported here may represent a milder form of osteocraniostenosis, or a new entity belonging to the same "family." Genealogical data are consistent with AR or XLR inheritance. No mutations were found in the coding sequence of filamin A.

Abnormalities, Multiple↗

PubMed2005

Hereditary thyroglossal duct cysts.

Thyroglossal duct cysts are one of the most commonly encountered benign neck lumps found in the paediatric population. Despite their relative frequency, reports of familial inheritance are rare. A total of 21 patients with hereditary thyroglossal duct cysts from seven families worldwide have been reported. The most common inheritance pattern is dominant, with a minority possibly representing a recessive aetiology. We describe a further instance of dominantly inherited thyroglossal duct cysts in two generations.

Child, Preschool↗

PubMed2003

Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign.

Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene result in a family of skeletal dysplasias, which comprise lethal (achondrogenesis type 1B and atelosteogenesis type 2) and non-lethal conditions (diastrophic dysplasia and recessive multiple epiphyseal dysplasia (rMED)). The most frequent mutation is R279W, which in a homozygous state results in rMED with bilateral clubfoot, MED, and "double layered" patella. We describe three patients with rMED caused by a previously unreported homozygous mutation in the DTDST gene. The three patients (from two families) were born to healthy, non-consanguineous parents. All developed signs of hip dysplasia in early childhood and two had episodes of recurrent patella dislocation. Two underwent bilateral total hip replacements at ages 13 and 14 years. The feet, external ears, and palate were normal. Stature was normal in all cases. Radiographs showed dysplastic femoral heads, mild generalized epiphyseal dysplasia, abnormal patella ossification, and normal hands and feet. Direct sequence analysis of genomic DNA demonstrated a homozygous 1984T > A (C653S) change in the DTDST gene in all patients. The clinically normal parents were heterozygous for the change. This is the first description of a homozygous C653S mutation of the DTDST gene. Hip dysplasia and patella hypermobility dominates the otherwise mild phenotype. These patients further expand the range of causative mutations in the DTD skeletal dysplasia family.

Adolescent↗