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Timothy Cox

Publications and source records attributed to Timothy Cox.

9 recordsLinked to original sources
PubMed2006

Pulmonary function assessment in an infant with Barnes syndrome: proactive evaluation for surgical intervention.

Our aim for this study was to report pulmonary mechanics in a neonate with a severe case of Barnes syndrome, a rare form of thoracolaryngopelvic dysplasia, and to use these data to guide ventilatory support and serve as a presurgical screening tool. A comprehensive pulmonary function evaluation was performed on a 36-day-old patient with Barnes syndrome who was being mechanically ventilated because of severe pulmonary distress secondary to thoracic dystrophy. The measurements consisted of respiratory volumes including functional residual capacity, ventilatory mechanics including compliance and resistance, and thoracoabdominal synchrony. Chest wall compliance was 64% below normal, and the thoracoabdominal motion was indicative of predominantly abdominal displacement during inspiratory breaths. The lungs were functioning at a low functional residual capacity, resulting in low lung compliance and increased pulmonary resistance. As a result of the evaluation, the patient was recommended for lateral thoracic expansion surgery and the ventilatory management was adjusted to focus on end-distending pressure support.

Abnormalities, Multiple↗
PubMed2006

A case of Beare-Stevenson syndrome with a broad spectrum of features and a review of the FGFR2 Y375C mutation phenotype.

We present a case of Beare-Stevenson syndrome with a broad range of phenotypic features including craniosynostosis, cutis gyrata, choanal stenosis, bifid scrotum with perineal hypospadias and a caudal appendage. The paternal age at the time of conception was 62 years consistent with a paternal age effect. Mutation analysis was undertaken and demonstrated the FGFR2 Y375C mutation. This case, one of only nine with molecular analysis, confirms the significant morbidity associated with this syndrome.

Abnormalities, Multiple↗
PubMed2005

Laser induced disruption of bacterial spores on a microchip.

We report on the development of a laser based spore disruption method. Bacillus globigii spores were mixed with a laser light absorbing matrix and co-crystallized into 200-microm-wide and 20-microm-deep nanovials formed in a polydimethylsiloxane (PDMS) target plate. Surface tension effects were exploited to effect up to 125-fold spore enrichment. When the target zones were illuminated at atmospheric pressure with pulsed UV-laser light at fluences below 20 mJ cm(-2) a change in spore morphology was observed within seconds. Post illumination PCR analysis suggests the release of endogenous DNA indicative of spore disruption. For laser fluences above 20 mJ cm(-2), desorption of spores and fragments was also observed even without a matrix being employed. Desorbed material was collected in a PDMS flowcell attached to the target plate during laser illumination. This opens up a route towards the direct extraction of released DNA in an integrated spore disruption-PCR amplification microchip device.

Bacillus↗
PubMed2005

Mild phenotypes in a series of patients with Opitz GBBB syndrome with MID1 mutations.

Opitz syndrome (OS; MIM 145410 and MIM 300000) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal (LTE) abnormalities, imperforate anus, developmental delay, and cardiac defects. The X-linked form (XLOS) is caused by mutations in the MID1 gene, which encodes a microtubule-associated RBCC protein. In this study, phenotypic manifestations of patients with and without MID1 mutations were compared to determine genotype-phenotype correlations. We detected 10 novel mutations, 5 in familial cases, 2 in sporadic cases, and 3 in families for whom it was not clear if they were familial or sporadic. The genotype and phenotype was compared for these 10 families, clinically diagnosed OS patients found not to have MID1 mutations, and 4 families in whom we have previously reported MID1 mutations. This combined data set includes clinical and mutation data on 70 patients. The XLOS patients with MID1 mutations were less severely affected than patients with MID1 mutations reported in previous studies, particularly in functionally significant neurologic, LTE, anal, and cardiac abnormalities. Minor anomalies were more prevalent in patients with MID1 mutations compared to those without mutations in this study. Female MID1 mutation carriers had milder phenotypes compared to male MID1 mutation carriers, with the most common manifestation being hypertelorism in both sexes. Most of the anomalies found in the patients of the present study do not correlate with the MID1 mutation type, with the possible exception of LTE malformations. This study demonstrates the wide spectrum of severity and manifestations of OS. It also shows that XLOS patients with MID1 mutations may be less severely affected than indicated in prior reports.

Exons↗
PubMed2005

Sickle cell disease: ischemia and seizures.

Although the prevalence of seizures in children with sickle cell disease (SCD) is 10 times that of the general population, there are few prospectively collected data on mechanism. With transcranial Doppler and magnetic resonance imaging (MRI) and angiography, we evaluated 76 patients with sickle cell disease, 29 asymptomatic and 47 with neurological complications (seizures, stroke, transient ischemic attack, learning difficulty, headaches, or abnormal transcranial Doppler), who also underwent bolus-tracking perfusion MRI. The six patients with recent seizures also had electroencephalography. Group comparisons (seizure, nonseizure, and asymptomatic) indicated that abnormal transcranial Doppler was more common in the seizure (4/6; 67%) and nonseizure (26/41; 63%) groups than in the asymptomatic (10/29; 34%) group (chi2; p = 0.045), but abnormal structural MRI (chi2; p = 0.7) or magnetic resonance angiography (chi2; p = 0.2) were not. Relative decreased cerebral perfusion was found in all seizure patients and in 16 of 32 of the remaining patients with successful perfusion MRI (p = 0.03). In the seizure patients, the perfusion abnormalities in five were ipsilateral to electroencephalographic abnormalities; one had normal electroencephalogram results. These findings suggest that vasculopathy and focal hypoperfusion may be factors in the development of sickle cell disease-associated seizures.

Adolescent↗
PubMed2002

Osteoclasts from mice deficient in tartrate-resistant acid phosphatase have altered ruffled borders and disturbed intracellular vesicular transport.

Tartrate-resistant acid phosphatase (TRAP) is an enzyme highly expressed in osteoclasts (OC) and chondroclasts. As an approach to pinpoint the function of TRAP in bone-resorbing osteoclasts, the morphological phenotypic alterations of bone and osteoclasts in mice with targeted disruption of the TRAP gene were assessed by quantitative histomorphometry and immunocytochemistry at the light microscopic and ultrastructural levels. TRAP-deficient mice display alterations in the epiphyseal growth plates as evidenced by increased height with disorganized columns of chondrocytes, in particular affecting the zone of hypertrophic chondrocytes, consistent with a disturbance of chondrocyte maturation and chondroclastic resorption at the epiphyseal/metaphyseal junction. TRAP -/- mice express an early onset osteopetrotic bone phenotype, apparent already at 4 weeks of age. The differentiation of OCs was apparently normal; however, the osteoclasts in TRAP-deficient mice were less active in terms of degradation or release of the resorption marker C-terminal type I collagen cross-linked peptide, indicative of an intrinsic defect. Ultrastructural morphometry disclosed that OCs from TRAP-deficient young mice exhibited an increased relative area of ruffled borders. Moreover, mutant OC accumulated cytoplasmic vesicles 200-500 nm in size in both ruffled border and basolateral parts of the cytoplasm, reflecting disturbed intracellular transport. The accumulated vesicles were not likely derived from the secretory pathway, since cathepsin K was detected at normal levels in the ruffled border area and matrix in TRAP -/- mice. In summary, the resorptive defect in TRAP-deficient OCs is reflected by a disturbance at the level of ruffled borders and intracellular transport vesicles. Consequently, accumulation of vesicles in the cytoplasm of mutant OCs indicates a novel function for TRAP in modulating intracellular vesicular transport in osteoclasts.

Acid Phosphatase↗
PubMedDate not supplied

Analysis of intracranial volume in apert syndrome genotypes.

OBJECTIVE: Apert syndrome is caused by a mutation of the fibroblastic growth factor type 2 gene and in nearly all of the cases where the mutation has been identified it occurs in one of two adjacent sites of the gene, either position 252 or position 253. There is currently uncertainty whether a worse neurosurgical outcome occurs in association with a particular genotype. We investigated whether there were clinically subtle (but relevant) morphological differences in the craniofacial skeleton, which would result in differences in the intracranial volume, which might account for apparent differences in surgical outcome. METHOD: Three-dimensional CT scans of pre-operative Apert syndrome whose genotype had been identified had the intracranial volume measured using the Cavalieri estimator with correction for partial voluming effects. The values were compared to age and sex normals and then the two genotypes compared. RESULTS: Intracranial volumes were measured for 22 cases, 16 with the 252 mutation and 6 with the 253 mutation. CONCLUSIONS: All cases except two had greater than their sex- and age-adjusted mean normal intracranial volumes. For the 252 and 253 genotypes there were no discernible differences in intracranial volumes between the two genotypes.

Acrocephalosyndactylia↗