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Biomedical subjects

K Bradshaw

Publications and source records attributed to K Bradshaw.

At least 19 recordsLinked to original sources
PubMed2006

Is optic nerve fibre mis-routing a feature of congenital stationary night blindness?

PURPOSE: To determine whether patients with congenital stationary night blindness (CSNB) have electrophysiological evidence of optic nerve fibre mis-routing similar to that found in patients with ocular albinism (OA). METHOD: We recorded the Pattern Onset VEP using a protocol optimised to detect mis-routing of optic nerve fibres in older children and adults. We tested 20 patients (age 15-69 yrs) with X-linked or autosomal recessive CSNB, 14 patients (age 9-56 yrs) with OA and 13 normally pigmented volunteers (age 21-66 yrs). We measured the amplitude and latency of the CI component at the occipital midline and over left and right occipital hemispheres. We also assessed the computed inter-hemispheric "difference" signal. Subjects with CSNB were classified as having the "complete" or "incomplete" phenotype on the basis of their ERG characteristics. Members of X-linked CSNB pedigrees underwent mutation screening of the NYX and CACNA1F genes. RESULTS: CI was significantly smaller over the ipsilateral hemisphere and more prominent over the contralateral hemisphere in OA patients compared with both controls and CSNB patients. In CSNB patients CI response amplitudes were not significantly different from controls but peak latency was prolonged at all three electrodes compared with controls. The inter-hemispheric "difference" signal was abnormal for the OA group but not for the CSNB group. Contralateral dominance of CI could be identified in the majority of OA patients and the "difference" signal was opposite in polarity for left compared with right eye stimulation in every patient in this group. Only 3 of 20 patients with CSNB showed significant inter-hemispheric asymmetry similar to that seen in the OA patients. All 3 CSNB patients with evidence for optic nerve fibre mis-routing had X-linked pedigrees: 2 had an identified mutation in the NYX gene but no mutation in either the NYX or CACNA1F genes was identified in the third. VEP evidence of optic nerve fibre mis-routing was present in 3 of the 11 subjects with "complete" phenotype and none of the 9 patients with "incomplete" phenotype CSNB. CONCLUSION: Mis-routing of optic nerve fibres does occur in CSNB but we found evidence of it in only 15% of our patients.

Adolescent↗
PubMed2005

Blue cone monochromatism: a phenotype and genotype assessment with evidence of progressive loss of cone function in older individuals.

AIM: To perform a detailed clinical and psychophysical assessment of the members of three British families affected with blue cone monochromatism (BCM), and to determine the molecular basis of disease in these families. METHODS: Affected and unaffected members of three families with BCM were examined clinically and underwent electrophysiological and detailed psychophysical testing. Blood samples were taken for DNA extraction. The strategy for molecular analysis was to amplify the coding regions of the long wavelength-sensitive (L) and middle wavelength-sensitive (M) cone opsin genes and the upstream locus control region by polymerase chain reaction, and to examine these fragments for mutations by direct sequencing. RESULTS: We have confirmed the reported finding of protan-like D-15 arrangements of patients with BCM. In addition, we have demonstrated that the Mollon-Reffin (MR) Minimal test is a useful colour-discrimination test to aid in the diagnosis of BCM. Affected males were shown to fail the protan and deutan axes, but retained good discrimination on the tritan axis of the MR test, a compelling evidence for residual colour vision in BCM. This residual tritan discrimination was also readily detected with HRR plates. In two families, psychophysical testing demonstrated evidence for progression of disease. In two pedigrees, BCM could be linked to unequal crossovers within the opsin gene array that resulted in a single 5'-L/M-3' hybrid gene, with an inactivating Cys203Arg mutation. The causative mutations were not identified in the third family. CONCLUSIONS: The MR test is a useful method of detecting BCM across a wide range of age groups; residual tritan colour discrimination is clearly demonstrated and allows BCM to be distinguished from rod monochromatism. BCM is usually classified as a stationary cone dysfunction syndrome; however, two of our families show evidence of progression. This is the first report of progression associated with a genotype consisting of a single 5'-L/M-3' hybrid gene carrying an inactivating mutation. We have confirmed that the Cys203Arg inactivating mutation is a common sequence change in blue cone monochromats.

Adolescent↗
PubMed2005

X-linked retinoschisis: clinical phenotype and RS1 genotype in 86 UK patients.

BACKGROUND: Inactivating mutations of the gene RS1 lead to X-linked retinoschisis, a progressive retinal dystrophy characterised by schisis within the inner layers of the neuroretina. The mutation spectrum is large and the phenotype variable. AIM: To determine whether there is a correlation between mutation type and disease severity. METHODS: We identified the causative mutation in 86 affected patients and examined each of these patients in detail. Different categories of mutation were compared for each phenotypic characteristic. RESULTS: We found a reduction in visual acuity with increasing age and worsening macular pathology in patients over 30 years old (p < or = 0.001), but there was no correlation between mutation type and severity of disease. Furthermore, we found a wide variation in phenotype even within families. CONCLUSIONS: Identifying the causative mutation in patients with X-linked retinoschisis is helpful in confirming diagnosis and in counselling of family members but cannot be used to predict prognosis for an individual patient.

Adolescent↗
PubMed2004

Full-field ERG responses recorded with skin electrodes in paediatric patients with retinal dystrophy.

PURPOSE: Assess ERG responses recorded with skin electrodes in children with retinal dystrophies. METHOD: ERG responses were recorded using skin electrodes in 17 healthy children and 43 paediatric patients with retinal dystrophy. Subjects were aged 4-14 years. ERG responses were recorded to full-field stimuli similar to those recommended in the ISCEV standard. The type of retinal dystrophy was classified on the basis of standard clinical criteria and the ERG responses were compared with those of the age-matched controls. RESULTS: ERG responses were abnormal in every patient. The specific type of ERG abnormality was also consistent with the clinical findings in the majority of patients. Rod responses were abnormal in every patient with a rod-cone dystrophy and cone responses were also abnormal in the majority of patients. Those patients with cone dystrophy or rod monochromatism had normal or near normal rod responses but sub-normal or absent cone responses. Patients with CSNB or XLRS had a sub-normal b-wave but normal amplitude a-wave. CONCLUSION: ERGs can be recorded successfully with skin electrodes in paediatric patientsand responses can aid the diagnosis of the type of retinal dystrophy.

Adolescent↗
PubMed2004

Autonomous activity of CaMKII is only transiently increased following the induction of long-term potentiation in the rat hippocampus.

A major role has been postulated for a maintained increase in the autonomous activity of CaMKII in the expression of long-term potentiation (LTP). However, attempts to inhibit the expression of LTP with CaMKII inhibitors have yielded inconsistent results. Here we compare the changes in CaMKII autonomous activity and phosphorylation at Thr286 of alphaCaMKII in rat hippocampal slices using chemical or tetanic stimulation to produce either LTP or short-term potentiation (STP). Tetanus-induced LTP in area CA1 requires CaMKII activation and Thr286 phosphorylation of alphaCaMKII, but we did not observe an increase in autonomous activity. Next we induced LTP by 10 min exposure to 25 mM tetraethyl-ammonium (TEA) or 5 min exposure to 41 mM potassium (K) after pretreatment with calyculin A. Exposure to K alone produced STP. These protocols allowed us to monitor temporal changes in autonomous activity during and after exposure to the potentiating chemical stimulus. In chemically induced LTP, autonomous activity was maximally increased within 30 s whereas this increase was significantly delayed in STP. However, in both LTP and STP the two-fold increase in autonomous activity measured immediately after stimulation was short-lived, returning to baseline within 2-5 min after re-exposure to normal ACSF. In LTP, but not in STP, the phosphorylation of alphaCaMKII at Thr286 persisted for at least 60 min after stimulation. These results confirm that LTP is associated with a maintained increase in autophosphorylation at Thr286 but indicate that a persistent increase in the autonomous activity of CaMKII is not required for the expression of LTP.

Animals↗
PubMed2004

Oligocone trichromacy: a rare and unusual cone dysfunction syndrome.

AIM: To describe the phenotype of a case series of six patients with oligocone trichromacy. METHODS: The six affected individuals underwent an ophthalmological examination, electrophysiological testing and detailed psychophysical assessment. RESULTS: All six affected patients had a history of moderately reduced visual acuity (6/12 to 6/24) from infancy, not improved by full spectacle correction. They complained of mild photophobia and they were not aware of any colour vision deficiency. They had no nystagmus and fundi were normal. Electrophysiological testing revealed either absent/profoundly reduced cone flicker responses or preserved but delayed and mildly reduced flicker responses. Colour vision was found to be within normal limits, but some patients showed mildly elevated discrimination thresholds along all axes. CONCLUSION: The largest case series to date of patients with oligocone trichromacy is presented. The electrophysiological findings suggest that there may be more than one disease mechanism. The mode of inheritance is likely to be autosomal recessive, and while previous reports have suggested that this disorder is stationary, in one of these families there is clinical evidence of progression.

Adolescent↗
PubMed2003

Genotype-phenotype correlation in British families with X linked congenital stationary night blindness.

AIM: To correlate the phenotype of X linked congenital stationary night blindness (CSNBX) with genotype. METHODS: 11 CSNB families were diagnosed with the X linked form of the disease by clinical evaluation and mutation detection in either the NYX or CACNA1F gene. Phenotype of the CSNBX patients was defined by clinical examination, psychophysical, and standardised electrophysiological testing. RESULTS: Comprehensive mutation screening identified NYX gene mutations in eight families and CACNA1F gene mutations in three families. Electrophysiological and psychophysical evidence of a functioning but impaired rod system was present in subjects from each genotype group, although the responses tended to be more severely affected in subjects with NYX gene mutations. Scotopic oscillatory potentials were absent in all subjects with NYX gene mutations while subnormal OFF responses were specific to subjects with CACNA1F gene mutations. CONCLUSIONS: NYX gene mutations were a more frequent cause of CSNBX than CACNA1F gene mutations in the 11 British families studied. As evidence of a functioning rod system was identified in the majority of subjects tested, the clinical phenotypes "complete" and "incomplete" do not correlate with genotype. Instead, electrophysiological indicators of inner retinal function, specifically the characteristics of scotopic oscillatory potentials, 30 Hz flicker and the OFF response, may prove more discriminatory.

Base Sequence↗
PubMed2003

A clinical and molecular genetic study of a rare dominantly inherited syndrome (MRCS) comprising of microcornea, rod-cone dystrophy, cataract, and posterior staphyloma.

AIM: To phenotype and genetically map the disease locus in a family presenting with autosomal dominant microcornea, rod-cone dystrophy, cataract, and posterior staphyloma. METHODS: Six affected and three unaffected members of the pedigree were examined. All individuals provided a history and underwent a full clinical examination with A-scan and B-scan ultrasonography and electrophysiological testing where appropriate. PCR based microsatellite marker genotyping using a positional candidate gene approach was then performed on DNA samples extracted from venous blood provided by each subject. RESULTS: The disorder is inherited as an autosomal dominant trait with variable expressivity and has a complex phenotype. Affected individuals had bilateral microcornea, pulverulent-like lens opacities, a rod-cone dystrophy and posterior staphyloma (MRCS). Using a positional candidate gene approach, the authors have evidence suggestive of linkage of this disorder to a region on 11q13 within the nanophthalmos 1 (NNO1) genetic interval. The small family size militates against achieving a LOD score of 3, but the haplotype data and the position of the putative MRCS locus within a known nanophthalmos locus are suggestive of linkage. A candidate gene within this region (ROM1) was screened and no mutations were found in affected members of the family. CONCLUSION: This rare developmental disorder has some phenotypic similarities to nanophthalmos and possibly maps to a locus within the genetic interval encompassing the NNO1 locus. Screening of candidate genes within this region continues.

Adolescent↗
PubMed2002

Progressive nodular histiocytosis in a child with a hypothalamic tumor.

We report a 13-year-old girl with multiple cutaneous histiocytic lesions, precocious puberty, growth hormone deficiency and a hypothalamic tumour. We conclude that she has progressive nodular histiocytosis, but this case illustrates the difficulty in differentiating the type II histiocytoses.

Adolescent↗
PubMed2001

Idiopathic central pontine myelinolysis in childhood.

Central pontine myelinolysis (CPM) is rare in childhood with only a few cases reported in world literature. We report a 7-year-old male who presented with acute ataxia, swallowing difficulties, dysarthria, and radiological features consistent with the disorder. He improved remarkably with oral prednisolone therapy and was almost back to normal by 2 weeks. A review of the literature is also included.

Anti-Inflammatory Agents↗
PubMed2001

Imaging the upper airways.

Radiological evaluation of the airway has been used as a screening tool and an adjunct to endoscopy for many years. It provides non-invasive data on the structure of the airway, often avoiding the risk of general anaesthesia. Standard radiographs provide some information on the intricate anatomy of the paediatric airway aided by fluoroscopy. More recently, CT and MRI are proving to have a valuable role and are approaching near endoscopic detail of airway anatomy. The purpose of this article is to highlight areas where radiology can aid in the evaluation of the airway of infants and children.

Adolescent↗
PubMed1999

Mutations of the XLRS1 gene cause abnormalities of photoreceptor as well as inner retinal responses of the ERG.

Intensity-series rod and cone ERGs were recorded in 19 patients with XLRS and 26 control eyes. All patients were examined by one ophthalmologist and diagnosed on the basis of fundus appearance and evidence of the disease in other males in the same family. Mutations in the XLRS1 gene have been identified in 15 of the patients. Dark-adapted ERGs were significantly different from controls for all test conditions and for both a-wave and b-wave responses. Abnormalities were detectable in all patients but there was considerable variation in the severity of abnormality. One third of the patients had the dark-adapted 'negative-wave' response typically associated with inner retinal disorder, but about one third showed only mild depression of the b-wave while the remainder had abnormally low a-waves in addition to depressed b-waves. Light-adapted responses were also affected and both a-wave and b-wave responses differed significantly from controls, but the 'negative-wave' response was not seen in any patient. The severity of the ERG abnormality did not correlate with the classification of fundus appearance or patient age suggesting that retinal function is relatively stable throughout life. The severity of ERG abnormalities did not correlate with the type of mutation and responses could differ between affected males within the same family. These results indicate considerable heterogeneity of ERG response without clinical, age or genetic correlate. The abnormal a-wave responses indicate that photoreceptor as well as inner retinal layer function may be affected in XLRS, at least in some patients.

Adult↗
PubMed1998

Ophthalmic manifestations of trisomy 8 mosaic syndrome.

Trisomy 8 mosaicism can present with a varied clinical picture. A significant number of cases have ocular manifestations. The most commonly reported in the literature have been corneal abnormalities and strabismus. We present a case of trisomy 8 mosaic syndrome with very different ophthalmic manifestations, some of which are previously unreported in the literature. The patient who was known to have trisomy 8 mosaic syndrome was referred with concerns about his visual abilities. He had a characteristic facial dysmorphism and other systemic features associated with this condition. Ophthalmic features included bilateral Duane's syndrome, bilateral myopic astigmatism, congenital pendular nystagmus, and macula hypoplasia. Electrodiagnostic tests confirmed extensive abnormality of cone function in both eyes. This case is discussed in relation to a review of the literature.

Astigmatism↗
PubMed1997

A Java-based multi-institutional medical information retrieval system.

JAMI (Java-based Agglutination of Medical Information) is designed as a framework for integrating heterogeneous information systems used in healthcare related institutions. It is one of the implementations under the W3-EMRS project 1 aimed at using the World Wide Web (Web) to unify different hospital information systems. JAMI inherited several design decisions from the first W3-EMRS implementation described in, including using the Web as the communication infrastructure and HL7 as the communication protocol between the heterogeneous systems and the W3-EMRS systems. In addition, JAMI incorporates the growing Java technologies and has a more flexible and efficient architecture. This paper describes JAMI's architecture and implementation. It also present two instances of JAMI, one for the integration of different hospital information systems and another for the integration of two heterogeneous systems within a single hospital. Some important issues for the further development of JAMI, including security and confidentiality, data input and decision support are discussed.

Computer Communication Networks↗