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Biomedical subjects

P A Fagan

Publications and source records attributed to P A Fagan.

At least 19 recordsLinked to original sources
PubMed1996

An NMR study of [d(CGCGAATTCGCG)]2 containing an interstrand cross-link derived from a distamycin-pyrrole conjugate.

Minor groove binding compounds related to distamycin A bind DNA with high sequence selectivity, recognizing sites which contain various combinations of A.T and G.C base pairs. These molecules have the potential to deliver cross-linking agents to the minor groove of a target DNA sequence. We have studied the covalent DNA-DNA cross-linked complex of 2,3- bis(hydroxymethyl)pyrrole-distamycin and [d(CGCGAATTCGCG)]2. The alkylating pyrrole design is based on the pharmacophore of mitomycin C and is similar in substructure to another important class of natural products, the oxidatively activated pyrrolizidine alkaloids. Ligand-DNA NOEs confirm that the tri(pyrrole-carboxamide) unit of the ligand is bound in the minor groove of the central A+T tract. Unexpectedly, it is shifted by 1 bp with respect to the distamycin A binding site on this DNA sequence. The cross-link bridges the 2-amino position of two guanine residues, G4 and G22. The C3.G22 and G4.C21 base pairs exhibit Watson-Crick base pairing, with some local distortion, as evidenced by unusual intensities observed for DNA-DNA NOE cross-peaks. The model is compared with a related structure of a cross-linked mitomycin C:DNA complex.

Base Sequence↗
PubMed1996

Mastoid surgery in the only hearing ear.

Every otologic procedure carries the risk of damage to the inner ear. On the other hand, cholesteatoma and uncontrolled tubotympanic disease can lead to partial or total sensorineural loss, as well as intracranial complications. Our experience of the surgical management of eight patients with an only hearing ear is presented. There were no dead ears in this series and no significant worsening of inner ear function. The air conduction pure-tone average was worse in two patients without change in bone conduction. Of the eight patients, six wear a hearing aid with success and two patients manage without an aid. The present small series confirms that patients at risk of anacusis from cholesteatoma or chronic suppurative otitis media can be offered, in experienced tertiary referral units, a safe method of stabilizing the ear and preserving useful hearing.

Adult↗
PubMed1996

Evolution of the management of hydrocephalus associated with acoustic neuroma.

The management of hydrocephalus in association with a cerebellopontine angle tumor is controversial. There is a widely held belief that initial therapy should always be directed toward treatment of hydrocephalus before definitive surgery. The potential problems of cerebrospinal fluid (CSF) shunting and drainage have to led to an evolution in the management of hydrocephalus at St. Vincent's Hospital. There is growing evidence that complete removal of cerebellopontine angle tumors will result in resolution of hydrocephalus without requiring other methods of CSF decompression. The authors present their experience of 14 patients with hydrocephalus found in a recent series of 104 consecutive cases of acoustic neuroma. This study has detected a significant correlation between hydrocephalus and increasing tumor size (P = .0234). The mean tumor size in this series was 3.8 cm. The series has also demonstrated that successful. safe, and complete tumor removal can be achieved without CSF drainage before surgery.

Adult↗
PubMed1996

A histopathologic review of temporal bone exostoses and osteomata.

It is widely accepted that external auditory canal exostoses and osteomata are separate clinical entities that differ in their gross appearance. Disagreement still exists as to whether external auditory canal exostoses and osteomata should be considered similar or separate histopathologic entities. A chart review was performed of all patients who had external auditory canal exostoses or temporal bone osteomata excised from January 1991 to November 1994 at St. Vincent's Hospital, Sydney. A histologic examination was undertaken with a blind study method of the patients whose pathological specimens were suitable for assessment. Eight exostoses and five osteomata were available for examination. The results of this study demonstrate that exostoses and osteomata of the external auditory canal cannot be reliably differentiated by routine histopathological examination.

Bone Neoplasms↗
PubMed1996

Hearing results following modified radical versus canal-up mastoidectomy.

Modified radical mastoidectomy (MRM) provides relatively safe surgical access for the removal of chronic middle ear and mastoid disease and gives reproducible results. However, it had been suggested that hearing may not be as good as that after "intact canal wall mastoidectomy" (ICWM). This paper reviews 153 tertiary referrals suffering from extensive disease who underwent MRM and compares their hearing results with those obtained by other authors using ICWM and MRM and a variety of reconstructive techniques. In this study there were no dead ears and no significant changes in bone conduction despite prolonged drilling and extensive disease. Hearing results after MRM were found to be better after primary surgery than after revision and better in the presence of an intact stapes. No rigid prostheses were used at first-stage surgery. There were no significant differences found between hearing results obtained by MRM in this series and other published results of canal wall down mastoidectomy and ICWM, irrespective of the use of ossicular replacement prostheses.

Adolescent↗
PubMed1995

The binding modes of a rationally designed photoactivated DNA nuclease determined by NMR.

The complex between the rationally designed synthetic DNA cleaving agent netropsin-diazene and the double-stranded DNA oligomer 5'-CGCAAAGGC-3'.5'-GCCTTTTGCG-3' was characterized by two-dimensional NMR spectroscopy in solution. Photolysis of netropsin-diazene bound to DNA generates a trimethylenemethane diradical intermediate that induces single-strand breaks in the DNA. The pi-diyl trimethylenemethane based compounds are a new class of DNA nucleases. We tested the following design criteria: (i) binding of the diazene and subsequent reactive diyl to the DNA, (ii) sequence selectivity in the ligand binding and (iii) prevention of diyl dimerization. Sixteen NOE derived ligand-DNA distance restraints were used to obtain the energy minimized model of the complex. The ligand is bound to the minor groove of the oligomer with the diazene at the 5' end of the A-tract in the predominant conformation of the complex. This form of the complex exchanges with a minor conformation in which the ligand is in the opposite orientation. The DNA maintains a B-form structure. Netropsin-diazene has fulfilled all of the design criteria, binding to the DNA duplex studied in the minor groove of the central AAAA tract in a 1:1 mode, preventing diyl dimerization and other side reactions from occurring.

Base Sequence↗
PubMed1995

The influence of race on the position of the jugular bulb.

The position of the jugular bulb (JB) is of great clinical significance to the otologist. A high and laterally situated jugular bulb may pose difficulties when dealing with the middle ear while a high and medially sited jugular bulb can create problems in neuro-otological surgery. This paper aims to study possible racial differences in the position of the jugular bulb. Fine-cut computed tomogram (CT) scans of temporal bones (in the axial plane) of 34 Caucasians and 34 Chinese were studied. The position of the jugular bulb was determined with reference to the midpoint of the lumen at the inferior limit of the cochlea (mpC). Of the 60 Caucasian and 58 Chinese temporal bones with identifiable jugular bulbs, 33 jugular bulbs of the Caucasian (55 per cent) and 34 jugular bulbs of the Chinese (58.6 per cent) were at the same height or higher than the mpC (p = 0.2; chi-squared test). The midpoint of the jugular bulb was 8.67 +/- 1.73 and 8.61 +/- 2.49 mm posterior to the mpC for the Caucasian and Chinese respectively (p = 0.2; t-test). However, the midpoint of the jugular bulb of eight Caucasian (24.2 per cent) and 22 Chinese (64.7 per cent) were medial to the mpC (p < 0.001; chi-squared test). Race does not influence the height of the jugular bulb nor its position in the sagittal plane but can influence whether a high jugular bulb is medially or laterally situated.

Adult↗
PubMed1995

Quantifying the Carhart effect in otosclerosis.

The Carhart effect consists of a depression in bone conduction thresholds in the presence of a conductive hearing loss. However, the mathematical relationship between the degree of conductive hearing loss and the degree of depression of bone conduction has not before been described. We have reviewed pre- and post-operative pure-tone audiograms performed on 102 consecutive patients having stapedectomy in an attempt to identify relationships between changes in bone conduction and air conduction and air-bone gap closure. Significant linear relationships were found between bone conduction and air conduction at 0.5. 1, 2 & kHz. Bone conduction was linearly related to air bone gap closure at 2 kHz.

Adolescent↗
PubMed1994

Large vestibular aqueduct syndrome and stapes fixation.

An abnormally large vestibular aqueduct has a well recognized association with inner ear anomalies and it has been assumed previously to be a variant of a Mondini type of deformity (Shuknecht, 1980; Emmett, 1985). The sole radiological finding in some patients with progressive sensorineural loss has been a large vestibular aqueduct (Valvassori and Clemis, 1978; Valvassori, 1983), which is now accepted as a separate clinical entity, i.e. the large vestibular aqueduct syndrome (LVAS). A case is presented which is believed to be the first reported with unilateral LVAS and stapes fixation and also the first stapes gusher described in association with LVAS.

Adult↗
PubMed1994

Low-grade myxoid chondrosarcoma of the temporal bone: differential diagnosis and report of two cases.

Skull base chondrosarcoma and chordoma are rare tumors that generally have a poor prognosis. In 1973, Heffelfinger et al described a chondroid variant of chordoma, called chondroid chordoma that was found to have a significantly better prognosis than classic chordoma. However, recent evidence suggests that many of the tumors diagnosed as chondroid chordoma may, in fact, be low-grade myxoid chondrosarcomas. This report presents the diagnosis and treatment of two cases of skull base tumor that were diagnosed preoperatively as schwannoma because they were thought initially to be centred on the jugular foramen. Initial histologic evaluation suggested chondroid chordoma, but immunohistologic techniques and a review of the literature led to a diagnosis of low-grade myxoid chondrosarcoma.

Adult↗
PubMed1994

Extensive facial nerve tumor with atypical histology: case report.

Primary facial nerve tumours are uncommon; most are benign schwannomas. Rare cases of malignant schwannomas and cellular schwannomas have been reported. The report describes a multicentric facial nerve tumor that did not fit well into any of these histopathologic categories. The tumor was removed in two stages and the patient has no clinical or radiographic evidence of recurrence 2 years after the initial procedure.

Child↗
PubMed1993

Facial neuroma of the cerebellopontine angle and the internal auditory canal.

Four cases of facial neuroma confined to the cerebellopontine angle and internal auditory canal are presented. Prior to surgery, three of these were diagnosed as an acoustic tumor. At operation the true diagnosis of facial neuroma was made. The operative procedure was recorded on film and videotape. The magnetic resonance imaging (MRI) and computed tomography (CT) scans were reviewed retrospectively. In the first three cases the tumor was not centered on the axis of the internal auditory canal (IAC), as would be typical of an acoustic neuroma, but instead occupied a position eccentric to this axis. In one case, this eccentricity was marked. A similar appearance in the fourth case enabled the true diagnosis of facial neuroma to be made before surgery. The postoperative behavior of the tumors was unpredictable. The patient with the largest tumor, which was debulked at operation, did not develop a facial palsy. However, a patient with a small tumor which was not biopsied, developed a delayed but complete paralysis from which she subsequently recovered. This small series suggests that it may be possible, by use of the appropriate imaging technique, to diagnose, preoperatively, a cerebellopontine angle facial neuroma which is otherwise indistinguishable from an acoustic neuroma.

Cerebellopontine Angle↗
PubMed1993

The management of multiple paraganglioma of the head and neck.

During the years 1984 to 1991, of 32 patients who had one large glomus or carotid body tumour, six were found to have other paragangliomas. Excluded from the above total of 32 are patients whose only lesion was a solitary glomus tympanicum. No two patients had identical problems and no pattern emerged on which patient management in any particular case could be based. The major problems associated with the tumours themselves and their treatment is the risk to hearing and the lower cranial nerves. Individual cases and their treatment are discussed.

Adult↗
PubMed1993

Catecholamine-secreting paraganglioma of the pterygopalatine fossa: case report.

The third reported case of a pheochromocytoma-like syndrome attributable to a catecholamine-secreting paraganglioma arising within the pterygopalatine fossa is documented. The 25-year-old, female subject was found to have raised levels of urinary catecholamines. At another center, a large vascular tumor was identified at lateral rhinotomy. Biopsy confirmed the diagnosis of paraganglioma. Tumor removal by a Fisch type-C approach to the sphenoid, parasellar region, and pterygopalatine fossa was complete and recovery uneventful.

Adult↗