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Biomedical subjects

P Phelps

Publications and source records attributed to P Phelps.

At least 19 recordsLinked to original sources

Injection of thyrotrophin-releasing hormone in turkey embryos elevates plasma thyroxine concentrations.

The effectiveness of thyrotrophin-releasing-hormone (TRH) as a secretagogue in turkey embryos was tested. Fertilized turkey eggs were injected with TRH after 24 d of incubation. In an experiment to determine an effective route and dose for TRH administration, it was shown that a single manual injection of 200 microL containing 2.15 microg of TRH, into the air cell or the same injection containing 5.0 microg through the bottom of the egg, was effective in elevating plasma concentrations of thyroxine (T4) 60 min after injection. In a second experiment, 5 microg of TRH in a volume of 200 microL was injected through the bottom of each egg. Injections were performed mechanically into eggs held in a commercial incubator. The injection increased blood plasma T4 for 5 h after a 30-min lag. Eggs from two genetic strains of turkeys were injected in Experiment 3. The TRH elicited a persistent response for 120 min from one strain but resulted in a slightly depressed response from the other, suggesting that subtle differences in the maturation of the hypothalamo-hypophyseal-thyroid axis may exist in commercial strains of turkeys. We concluded that TRH is an effective secretagogue for T4 in 24-d-old turkey embryos.

Animals↗

Eighth nerve aplasia and hypoplasia in cochlear implant candidates: the clinical perspective.

OBJECTIVE: To identify the clinical and radiologic characteristics of aplasia and hypoplasia of the eighth nerve. STUDY DESIGN: Retrospective case-note review. SETTING: Cochlear implant program. PATIENTS: All children at the authors' institution in whom the cochlear implant assessment failed because of absence or hypoplasia of the eighth nerve. INTERVENTION: Computed tomography of petrous bones and magnetic resonance imaging of the brain. MAIN OUTCOME MEASURES: Presence or absence of eighth nerve and other radiologic factors contraindicating implantation. RESULTS: Of 143 cochlear implant candidates, 237 were judged ineligible for cochlear implantation. The preimplant assessment failed in 10 candidates of 143 because of bilateral aplasia or hypoplasia of the eighth nerve (7 cases) or unilateral aplasia or hypoplasia of the eighth nerve and a contraindication to operation on the other side (3 cases). The aplasia or hypoplasia of the eighth nerve was confirmed by magnetic resonance imaging in seven cases (5%): six were syndromic (3 CHARGE, 1 VATER-RAPADILLINO, 1 Möbius, 1 Okihiro), and one was nonsyndromic autosomal-recessive. All seven children had delayed motor milestones and absence of auditory brainstem responses. CONCLUSION: Aplasia and hypoplasia of the eighth nerve are not uncommon in pediatric cochlear implant candidates, particularly in the presence of a syndrome such as CHARGE. Magnetic resonance imaging of the brain is mandatory before implantation because it can identify the presence or absence of the eighth nerve. Parents of children with profound hearing loss, delayed motor milestones, absence of auditory brainstem responses, and a syndromic diagnosis, should be made aware of this possible abnormality.

Brain↗

Origin and spread of allergic fungal disease of the nose and paranasal sinuses.

Although expansion of bony walls occurs in allergic fungal disease of the nose and paranasal sinuses by increased mucus secretion and fungal growth, the latter is apparently confined to the lumen and does not invade the tissues. Nevertheless, spread of the disease process from paranasal sinuses to orbit, cheek and intracranial cavity is well described. An imaging and histopathological study was carried out in 16 cases to determine how the disease originates and spreads. The infection starts in the nasal cavity, the lumen of a sinus or in a seromucinous gland or duct. A thin vascular zone of intense allergic inflammation surrounds the infected mucin. Erosion of bone takes place focally, probably by substances produced by the inflammatory tissue, allowing intromission by the thin vascular layer together with its underlying fungus-containing mucus and so extension of the disease process through the eroded bone.

Adult↗

Temporal bone computed tomography findings in bilateral sensorineural hearing loss.

AIM: To examine the yield of computed tomography (CT) of the temporal bones when investigating sensorineural hearing loss (SNHL) and to identify factors associated with CT findings. METHODS: Retrospective analysis of 116 consecutively investigated children with bilateral SNHL at the audiology department of Great Ormond Street Hospital, London. Main outcome measures were CT results, hearing loss parameters, history, and clinical examination. RESULTS: A total of 33 (28.4%) CT scans were identified as abnormal. Children with profound and/or progressive hearing loss and/or craniofacial abnormalities were more likely to have an abnormal CT scan and together accounted for 25 abnormal CT scans. Sex, consanguineous parents, or family history of SNHL were not associated with CT findings. Dilated vestibular aqueduct was significantly correlated with the presence of progressive SNHL. CONCLUSIONS: All children with SNHL should undergo radiological investigation of the petrous bones/inner ear; abnormalities are more likely to be found in cases with craniofacial abnormalities, or profound or progressive hearing loss. The decision whether to perform a CT or magnetic resonance imaging will depend on scanner availability, expertise, and management considerations, but cochlear implant candidates will require both.

Child↗

Unilateral sensorineural hearing loss and its aetiology in childhood: the contribution of computerised tomography in aetiological diagnosis and management.

OBJECTIVES: The objective of this study was to identify factors correlated with the CT outcome and to examine the contribution of the CT scan in the aetiological diagnosis and management of unilateral sensorineural hearing loss in childhood. METHODS: The records of 35 consecutively investigated patients by the Audiology Department of Great Ormond Street Hospital between January 1996 and June 1998 were reviewed. The CT results, population sample characteristics, initiation of further investigations after the CT results and management decisions based on the CT results were tabulated and analysed. RESULTS: In a series of 35 consecutively investigated children with unilateral sensorineural hearing loss, 11 CT scans were identified as abnormal. The CT findings were: labyrinthitis ossificans (3), unilaterally dilated vestibular aqueduct (2), bilaterally dilated vestibular aqueduct (2), unilateral deformity of the cochlea ('Mondini') (1), unilateral severe labyrinthine dysplasia (1), unilateral markedly narrow internal acoustic meatus (1), bilaterally dilated lateral semicircular canals (1). The presence of progressive hearing loss was a significant predictor of abnormal CT outcome, while the severity of hearing loss was not. The CT scans offered valuable information regarding the aetiological diagnosis in all cases and, in addition, prompted the appropriate vestibular rehabilitation in three cases, further investigations in four (with dilated vestibular aqueduct) and hearing preservation counselling in two (bilateral DVA) (seven out of 35 = 20%). CONCLUSION: All children with unilateral sensorineural hearing loss should have a CT scan of the petrous pyramids/IAMs performed at some stage, as not only aetiology but also prognosis and management of these cases may be significantly influenced by the CT outcome.

Adolescent↗

Juvenile angiofibroma: the lessons of 20 years of modern imaging.

Seventy-two patients with juvenile angiofibroma have been investigated by computerized tomography (CT) and/or magnetic resonance imaging (MRI) over a period of 20 years. The evidence from these studies indicates that angiofibroma takes origin in the pterygo-palatine fossa at the aperture of the pterygoid (vidian) canal. An important extension of the tumour is posteriorly along the pterygoid canal with invasion of the cancellous bone of the pterygoid base, and greater wing of the sphenoid (60 per cent of patients). Distinctive features of angiofibroma are the high recurrence rate, and the rapidity with which many tumours recur. It is postulated that the principal determinant of recurrence is a high tumour growth rate at the time of surgery coupled with incomplete surgical excision. The inability to remove the tumour in toto is principally due to deep invasion of the sphenoid, as described above. In this series 93 per cent of recurrences occurred with this type of tumour extension. A contributory cause in these patients is the use of pre-operative embolization. The treatment implications of these findings are examined.

Adolescent↗

In ovo vaccination technology.

More than 80% of the U.S. broiler industry has converted to the in ovo vaccination process for control of Marek's disease. Providing certain criteria are met, including timing and site of vaccine placement, vaccine mixing, machine sanitization, and hatchery management specifications, this has proven to be an efficacious and convenient method of vaccination. Efforts to extend the technology for other viral vaccines including Newcastle, bronchitis and bursal disease, and bacterial and parasitic vaccines are in progress. Collectively, these studies demonstrate that in ovo vaccination technology using approved vaccine is a safe, efficacious, and convenient method for vaccination of poultry.

Animals↗

Assessment of developmental changes in chicken and turkey insulin-like growth factor-II by homologous radioimmunoassay.

The development of a homologous RIA for chicken insulin-like growth factor-II (cIGF-II) and its application to investigate the developmental changes in IGF-II in the chicken and turkey are described. A double-antibody RIA has been developed using recombinantly derived cIGF-II as antigen, radiolabelled tracer and standard. Serial dilutions of chicken and turkey plasma were parallel to serial dilutions of cIGF-II standard. We have also established that acid/ethanol extraction of chicken and turkey plasma reduced possible interference of insulin-like growth factor-binding proteins in the RIA. Consumption of a low-protein diet by male chickens lowered plasma IGF-I twofold, whereas IGF-II levels were unchanged. Food withdrawal evoked an increase in circulating IGF-II, while IGF-I levels were reduced. Refeeding returned both growth factors to normal circulating concentrations. During chick embryo incubation, plasma IGF-II levels were tenfold higher than those of IGF-I. In the turkey embryo, plasma IGF-II concentrations were higher than those of IGF-I. During the post-hatch period. IGF-II levels declined with age in chickens. In the growing turkey, IGF-II levels were consistently higher than IGF-I levels. The application of the homologous RIA to monitor plasma levels during embryonic development and post-hatch growth in avian species will provide more accurate comparisons of results from studies on the role of IGF-II in growth and metabolism of domestic birds.

Animals↗

Applications in in ovo technology.

By mid-August 1995, 55% of broiler embryos in North America were vaccinated for Marek's disease using the INOVOJECT system, with 201 INOVOJECT machines placed with 16 of the top 25 poultry producers, providing the industry with the capacity to inject in excess of 400 million eggs per month or about 5 billion eggs per annum. In ovo administration of a bursal disease antibody-infectious bursal disease virus (BDA-IBDV) complexed vaccine to specific-pathogen-free (SPF) embryos was safer and more potent than conventional IBDV vaccine alone because it delayed the appearance of bursal lesions, produced no early mortality, produced higher geometric mean antibody titers against IBDV, and generated protective immunity against challenge. In ovo administration of a BDA-IBDV complexed vaccine to broiler embryos generated antibody titers against IBDV sooner than conventional virus vaccinates, and generated protective immunity against challenge Direct DNA injection of plasmid DNA encoding beta-galactosidase into breast muscle in ovo and posthatch was an effective means to achieve both gene transfer and expression, with potential for the development of gene vaccines using plasmids encoding protective antigens from poultry pathogens. In ovo administration of 800 U chicken myelomonocytic growth factor (cMGF), a chicken hematopoietic cytokine for cells of the monocytic-granulocytic lineages, significantly reduced mortality associated with Escherichia coli exposure within the hatcher when compared to PBS controls (6.1 vs 12.4, P < or = 0.05), but not when compared to a yeast expression control. A procedure was developed enabling injection prior to the onset of incubation without compromising embryo viability. This in ovo injection process has opened up the window of embryo development during incubation for intervention, as illustrated by the 100% male phenotype produced in chicks hatching from eggs injected with aromatase inhibitor prior to incubation. These data illustrate some of the in ovo applications presently in use by the poultry industry, and under development or in research at EMBREX.

Animals↗

Ear-nose-throat abnormalities in the CHARGE association.

A comprehensive evaluation of the otolaryngological abnormalities in 50 patients with colobomata, heart defect, atresia of the choanae, retarded growth or development, genital hypoplasia, and ear anomalies or deafness (CHARGE) was performed. All the patients had ear abnormalities; 96% (48/50) had malformed pinnae, and 54% (27/50) had facial nerve palsies. Only 8% (4/50) had normal hearing, the commonest hearing defect being severe conductive or mixed loss. Eighty-four percent (42/50) of computed tomographic scans of the temporal bone were abnormal, the characteristic abnormality being the combination of a hypoplastic incus and absent semicircular canals. Eighty-six percent (43/50) of patients had upper airway abnormalities. Posterior choanal abnormalities occurred in 56% (28/50), and 42% (21/50) had retrognathia leading to intubation difficulties. Laryngotracheal abnormalities occurred in 38% (19/50), and 14% (7/50) required tracheostomies. Careful upper airway assessment is essential to avoid potentially lethal complications such as aspiration.

Abnormalities, Multiple↗

Phenotypic characterization of copper-resistant mutants of Methylosinus trichosporium OB3b.

Cultures of Methylosinus trichosporium OB3b grown in the presence of very low concentrations of copper synthesize a soluble methane monooxygenase (sMMO) that efficiently catalyzes the oxidation of trichloroethylene and other organic pollutants. Recently, we isolated five M. trichosporium OB3b mutants that express sMMO activity when grown in the presence of elevated copper concentrations (P.A. Phelps, S. K. Agarwal, G. E. Speitel, Jr., and G. Georgiou, Appl. Environ. Microbiol. 58:3701-3708, 1992). Here we show that, in contrast to the results for the wild-type cells, the addition of copper to mutant cultures grown on methane and nitrate as the nitrogen source has no noticeable effect on the growth rate and sMMO expression. In vitro experiments indicated that the copper-resistant phenotype does not arise from an increased stability of sMMO to copper deactivation. Furthermore, the mutant cultures exhibit altered speciation of copper in the extracellular fluid and have substantially decreased levels of cell-associated copper. On the basis of these results, we propose that the mutant phenotype arises from defects in copper uptake and metabolism rather than from changes in sMMO expression or enzyme stability.

Biodegradation, Environmental↗

Neuro-otological function in X-linked hearing loss: a multipedigree assessment and correlation with other clinical parameters.

Auditory and vestibular investigations were carried out in 19 affected men and 13 obligate female carriers of 7 pedigrees with nonsyndromic hearing loss segregating as an X-linked trait. In addition, high resolution computerised tomographic scanning was carried out in 24 affected males and 12 obligate female carriers. The neuro-otological results confirm that non syndromic X-linked hearing loss is a clinically heterogeneous condition, but radiological assessment of the cochlea revealed two distinct groups: a normal group, and an abnormal group characterised by a bulbous internal auditory meatus, a dilated facial nerve canal and incomplete separation of the basal coil of the cochlea from the internal auditory meatus. Within a given pedigree there was marked consistency of the presence or absence of the CT scan abnormality in the affected males. One third of the obligate female carriers of the radiologically abnormal pedigrees were shown to have a similar abnormal finding, but as two thirds were normal, radiological examination did not predict carrier status. In the affected men, pure tone audiometric data did not correlate with the radiological abnormality, whereas vestibular function was strikingly correlated, being normal in all but one case in pedigrees with normal radiology and absent, or grossly impaired, in the pedigrees with abnormal radiology. Neuro-otological abnormalities were documented in approximately two thirds of the obligate female carriers, but were insufficiently frequent in occurrence or specific in type to be of predictive value.

Adolescent↗

A family with X-linked deafness showing linkage to the proximal Xq region of the X chromosome.

Linkage analysis has been carried out in a family with severe congenital sensorineural deafness with a structural abnormality of the inner ear. Recombinations show the gene responsible for deafness in this family to lie between the loci DXS255 (Xp11.22) and DXS94 (Xq22). Close linkage was found to locus DXS159 (cpX289) in Xq12, with a LOD score of 3.155 and 0 recombination. This location is consistent with other linkage studies of X-linked deafness.

Chromosome Mapping↗

Clinical and genetic heterogeneity in X-linked deafness.

The use of molecular techniques in respect of the rare X-linked non-syndromic form of genetic deafness demonstrates that this is a genetically heterogeneous disorder, with evidence for at least two separate gene loci on the X chromosome. Audiological heterogeneity in this condition is emphasized by the observation of both mixed deafness and sensorineural deafness in pedigrees showing evidence for linkage to Xq13-q21. The importance and shortcomings of the audiogram in assessing females who are known gene carriers is discussed.

Adolescent↗

A multipedigree linkage study of X-linked deafness: linkage to Xq13-q21 and evidence for genetic heterogeneity.

A locus for X-linked nonsyndromic deafness has previously been allocated to the Xq13-q21 region based on linkage studies in two separate pedigrees. This has been substantiated by the observation of deafness as a clinical feature of male patients with cytogenetically detectable deletions across this region. The question of a second locus for deafness in this chromosomal region has been raised by the audiologically distinct nature of the deafness in some of the deleted patients compared to that observed in those patients upon whom the linkage data are based. We have performed detailed clinical evaluation and linkage studies on seven pedigrees with nonsyndromic X-linked deafness and conclude that there is evidence for at least two loci for this form of deafness, including one in the Xq13-q21 region. We have observed different radiological features among the pedigrees which map to Xq13-q21, suggesting that even among these pedigrees the deafness is due to different pathological processes. Given these findings, we suggest that the classification of nonsyndromic X-linked deafness based solely on audiological criteria may need to be reviewed.

Chromosome Mapping↗

Patulous eustachian tube: a radiological perspective.

The diagnosis of a patulous Eustachian tube relies mainly upon the history, examination and a clinical awareness of the condition. More recently, objective tests such as tympanometry and sonotubometry have been shown to be useful in confirming the diagnosis. This paper describes how computed tomographic imaging may also be useful in aiding the diagnosis. Supporting this, clinical cases of patulous tubes are demonstrated radiologically associated with congenital hemifacial microsomia and following radiotherapy for a nasopharyngeal carcinoma. The role of computed tomographic imaging in the diagnosis, research and monitoring of treatment for his condition is discussed.

Adult↗