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Biomedical subjects

P J Bradley

Publications and source records attributed to P J Bradley.

At least 19 recordsLinked to original sources

An audit of clinical resources available for the care of head and neck cancer patients in England.

AIMS: Thirty-four cancer networks are now responsible for the delivery of head and neck cancer services in England. A survey of all cancer networks was carried out to define the services available for the diagnosis, treatment and support of patients with head and neck cancer. MATERIALS AND METHODS: Fifty-two cancer units were identified in England from the Cancer Services Collaborative 'Improvement Partnership', and approached through a variety of methods. One questionnaire was circulated to all 34 network leads to establish the services and resources in each network. A second questionnaire was circulated to all known head and neck teams in the UK. RESULTS: Multidisciplinary team (MDT) working was evident in all centres, although frequently the MDT was not fully staffed, especially in areas of national staff shortages, such as in pathology, radiology, dietetics and speech therapy. Rapid referral pathways were present for initial assessment of patients, but clinically significant delays were identified in complex investigations, access to intensive care beds and oncological care, especially radiotherapy. CONCLUSION: Major changes in service configuration are likely to be required if the current national targets of time to diagnosis and treatment are to be met.

England↗

Occult carotid pseudoaneurysm following streptococcal throat infection.

Pseudoaneurysm of the internal carotid artery (PAICA) is a rare complication of neck space infection. An 8-year-old girl presented with odynophagia (painful swallowing), trismus and left peritonsillar swelling. Abscess was suspected, but aspiration was dry. The PAICA was diagnosed on computed tomography. The aneurysm and involved left internal carotid artery were occluded endovascularly. She has made an uneventful recovery.

Aneurysm, False↗

An audit of clinical resources available for the care of head and neck cancer patients in England.

OBJECTIVE: To undertake a postal survey of cancer networks to define the services available for the diagnosis, treatment and support of patients with head and neck cancer in England. FINDINGS: Thirty-four cancer networks are now responsible for the delivery of head and neck cancer services in England and 52 cancer units responded to our questionnaire. Multidisciplinary team working was evident in all centres. However such team working was not always fully staffed, especially in areas of national staff shortages such as pathology, radiology, dietetics and speech therapy. Rapid referral pathways were present for initial assessment of patients but clinically significant delays were identified in the provision of complex investigations, in access to intensive care beds and for oncological care--especially radiotherapy. CONCLUSIONS: Major changes in service configuration are likely to be required if the current national targets of time to diagnosis and treatment are to be met.

Cancer Care Facilities↗

Nasal dermoid sinus cysts in adults.

Nasal dermoid sinus cysts (NDSC) are rare congenital lesions that most frequently present in children, but have been reported in adults. This article reviews adult (more than 16 years of age) nasal dermoid sinus cysts as they present, their radiological investigation, surgical approach and outcome. Thirty-eight previously published cases are reviewed, to which a further six cases are added. All 44 cases are tabulated and reviewed. The risk of intracranial extension is 27.5 per cent, especially men with a dermal sinus. Recurrences are likely if the NDSC is not completely excised. Curative treatment is surgical. It is recommended that all adults who present with a dermal cyst and/or sinus in the region of the nasal dorsum should be investigated by computed tomography (CT) and/or magnetic resonance (MRI). This is to delineate deep tissue involvement and to exclude a possible associated intracranial extension, prior to recommending surgical excision.

Adolescent↗

Management of chronic parotitis: a review.

Chronic parotitis is an insidious inflammatory disorder, which is characterized by a recurrent, often painful, swelling of the gland or glands. Sialography remains the investigation of choice. Diagnostic siladenoscopy may complement or supersede sialography as the diagnostic procedure of choice, as more experience is gained in this technique and its use becomes more widespread. The management options are conservative or surgical, but controversy exists regarding the timing and method of surgical intervention. The surgical methods that have been described include injection of methyl violet - a sclerosing agent, ductal ligation, ductoplasty, tympanic neurectomy, and parotidectomy. Parotidectomy is considered the ultimate surgical option but because of its significant morbidity the exact technique and procedure that should be used remains contentious.

Anti-Inflammatory Agents↗

Are autopsies useful? Do premorbid findings predict postmortem results in head and neck cancer patients?

A total of 53 autopsies were analysed in patients with head and neck squamous carcinoma. The discordance rate, that is the proportion of autopsies that revealed new information, was 53%. One-third of patients did not die of cancer. Clinical findings either misdiagnosed or under-diagnosed loco regional disease in 34% of cases, and distant malignant disease in 36% of cases. It appears that the autopsy reveals new and useful information in the head and neck cancer patient, and consent should be sought.

Aged↗

The pro region of Toxoplasma ROP1 is a rhoptry-targeting signal.

The rhoptries of Toxoplasma gondii are regulated secretory organelles involved in the invasion of host cells. Rhoptry proteins are synthesised as pre-pro-proteins that are processed first to pro-proteins upon entrance into the secretory pathway, then processed again to their mature forms late in the secretory pathway. The pro-mature processing site of the rhoptry protein ROP1 has been determined, paving the way for understanding the role of the pro region in rhoptry protein function. We demonstrate here that the ROP1 pro region is sufficient for targeting a reporter protein (amino acids 34-471 of the Trypanosoma brucei VSG117 protein) to the rhoptries. These results, together with our previous work showing that rhoptry targeting is unaffected by deletion of the pro region, indicate that the ROP1 protein contains at least two signals that can function in rhoptry targeting.

Animals↗

MIB-1 and p53 expression in radiotherapy-resistant T1aN0M0 glottic squamous cell carcinoma.

Radiotherapy of T1aN0M0 glottic carcinoma results in a local control rate of 80-94%. This homogenous group, which is the earliest recognisable invasive malignancy in the head and neck region, provides a 'unique model' for studying possible biological markers of radiosensitivity. p53 and MIB-1 were investigated as possible markers of radiosensitivity in such a group. In all, 107 patients with T1aN0M0 glottic squamous cell carcinoma treated with radiotherapy were identified. Cases not responsive to radiotherapy were compared with matched radiosensitive controls by immunohistochemistry using monoclonal primary antibodies to MIB-1 (n = 18; controls = 10) and p53 (n = 6; controls = 11). No significant difference in p53 expression was noted between the two groups (P = 0.73). A greater MIB-1 expression was found in the radiosensitive group but only a trend towards significance was observed (P = 0.06). MIB-1 is a potential marker of radiosensitivity. A larger multicentre study is required for a more definitive answer.

Antibodies, Monoclonal↗

Aggressive sino-nasal non-Hodgkin's lymphoma diagnosed in Nottinghamshire, UK, between 1987 and 1996.

In the 10-year period 1987 to 1996, 24 patients were diagnosed with aggressive non-Hodgkin's lymphoma of the nasal cavities or paranasal sinuses. The disease occurred in a relatively elderly population of median age 72 years (range 42 to 96) with a male predominance (male 15; female nine). The histology on review was mostly of the large B-cell subtype (21 patients); peripheral T-cell subtype (one), anaplastic large cell of T-cell type (one) and T/natural killer cell nasal lymphoma (one). The disease was localized in 20 patients (Stage IEA). The overall survival at 5 years was 40% (95% confidence interval (CI) 19-61); at 10 years it was 33% (95% CI 12-54). The cause-specific survival (excluding deaths from causes other than lymphoma) at 5 years and 10 years was 62% (95% CI 39-86).

Adult↗

Pilomatrixoma in the parotid region.

Pilomatrixoma is a benign neoplasm of the hair follicle that may present to the otolaryngologist as a palpable swelling in the head and neck area. The correct diagnosis may be difficult to confirm when it presents in the region of the parotid. The use of fine needle aspiration cytology (FNAC) and diagnostic imaging may help confirm the diagnosis. The correct treatment is surgical. However, should the tumour recur then the possibility of malignancy should be considered.

Adolescent↗

Benign salivary gland disease.

The majority of benign clinical problems that present affect the major salivary glands--parotid and submandibular. However, there are numerous minor salivary glands located in the mucosa of the head and neck which have the same predilection to the same diseases that affect the major glands but to a lesser frequency.

Adult↗

Competition and protease sensitivity assays provide evidence for the existence of a hydrogenosomal protein import machinery in Trichomonas vaginalis.

Hydrogenosomes are double membrane bounded redox organelles found in a number of amitochondriate protists and fungi. They are involved in carbohydrate metabolism and ATP synthesis and thus resemble mitochondria. Molecular analysis of the hydrogenosomal heat shock proteins Hsp70, Hsp60 and Hsp10 in Trichomonas vaginalis, one of the deepest-branching eukaryotes known to date, has revealed that these group exclusively with mitochondrial heat shock proteins. This finding indicates strongly that a progenitor organelle which gave rise to contemporary mitochondria and hydrogenosomes existed early in eukaryotic life. This hypothesis is further supported by similarities of hydrogenosomal and mitochondrial biogenesis. It was shown that T. vaginalis hydrogenosomal proteins are synthesized on free ribosomes in the cytosol with an N-terminal presequence that carries targeting information and is cleaved upon import into the organelle. Furthermore, as in mitochondrial import, hydrogenosomal protein import requires ATP, an electrochemical transmembrane potential and cytosolic protein factor(s). Here we demonstrate that inhibition of hydrogenosomal protein import occurs (i) in the presence of a synthetic presequence peptide and (ii) after pretreatment of hydrogenosomes with the protease trypsin. Trypsin pretreatment affects two hydrogenosomal membrane proteins of 31 and 70 kDa, respectively. Thus, we present evidence that import is saturable and that proteinaceous hydrogenosomal import receptor(s) exist. These results are a first step towards a characterization of the hydrogenosomal import machinery which should provide further insights into the relationship of hydrogenosomes and mitochondria and the evolution of protein targeting into organelles of endosymbiotic origin.

Animals↗

A randomised clinical trial of turbinectomy for compensatory turbinate hypertrophy in patients with anterior septal deviations.

Turbinectomy is performed at the time of nasal septal surgery by many otolaryngologists. One reason given for this procedure is the presence of a hypertrophied contralateral inferior turbinate. A randomised trial was undertaken to evaluate the relief of nasal obstruction following contralateral turbinectomy with septal surgery. Patients presenting with nasal obstruction who had a unilateral septal deviation and contralateral inferior turbinate enlargement were prospectively randomized to contralateral turbinectomy or no turbinate surgery at the time of septal surgery. Questionnaires and active anterior rhinomanometry were used for evaluation. Twenty-six patients (mean age 31 years) demonstrated a reduction in subjective and objective measures of nasal obstruction (P < 0.05) 8 weeks after operation. There was no intergroup difference, the median total decongested nasal resistance postoperatively in the non-turbinectomized patients was 0.17 kPal-1 s and 0.21 kPal-1 s in the turbinectomized patients. Contralateral inferior turbinectomy does not add to the relief of nasal obstruction beyond that attained by septal surgery in these patients.

Adolescent↗

Non-Hodgkin's lymphoma of the sinonasal tract.

OBJECTIVES: A review of the presenting features, management, and outcome of extranodal non-Hodgkin's lymphoma (NHL) of the sinonasal tract during a 10-year period in Nottingham, UK. STUDY DESIGN: Twenty-four patients received a diagnosis of extranodal NHL of the nasal cavity, paranasal sinuses, or both, from 1987 to 1996. The patients' data were collected prospectively in the Nottinghamshire Lymphoma Registry. METHODS: All patients' records and their histology were reviewed along with data entered into the Nottinghamshire Lymphoma Registry, noting the patient's age, sex, presenting symptoms and signs, staging, computed tomography findings, histology, treatment, complications, and outcome. RESULTS: The 24 patients with extranodal NHL of the sinonasal tract represent 1.63% of the 1,457 patients with NHL seen in the 10-year period of this study in Nottinghamshire. The median age was 72 years (range, 42-96 y), with a male dominance (male-to-female ratio: 15:9). Most patients presented with nonspecific nasal symptoms such as nasal obstruction and epistaxis. Only one patient had a relapse involving the central nervous system after treatment. All the histology was reviewed and showed a predominance of large B-cell subtype (21 patients). The overall 5-year survival was 40% (95% CI, 19%-61%) and 33% for 10-year (95% CI, 12%-54%). The cause-specific survival at 5 years and 10 years was 62% (95% CI, 39%-86%). CONCLUSIONS: A high degree of suspicion and appropriate use of computed tomography scans and surgical biopsy are the keys to the management of NHL.

Adult↗

Toxoplasma gondii homologue of plasmodium apical membrane antigen 1 is involved in invasion of host cells.

Proteins with constitutive or transient localization on the surface of Apicomplexa parasites are of particular interest for their potential role in the invasion of host cells. We describe the identification and characterization of TgAMA1, the Toxoplasma gondii homolog of the Plasmodium apical membrane antigen 1 (AMA1), which has been shown to elicit a protective immune response against merozoites dependent on the correct pairing of its numerous disulfide bonds. TgAMA1 shows between 19% (Plasmodium berghei) and 26% (Plasmodium yoelii) overall identity to the different Plasmodium AMA1 homologs and has a conserved arrangement of 16 cysteine residues and a putative transmembrane domain, indicating a similar architecture. The single-copy TgAMA1 gene is interrupted by seven introns and is transcribed into an mRNA of approximately 3.3 kb. The TgAMA1 protein is produced during intracellular tachyzoite replication and initially localizes to the micronemes, as determined by immunofluorescence assay and immunoelectron microscopy. Upon release of mature tachyzoites, TgAMA1 is found distributed predominantly on the apical end of the parasite surface. A approximately 54-kDa cleavage product of the large ectodomain is continuously released into the medium by extracellular parasites. Mouse antiserum against recombinant TgAMA1 blocked invasion of new host cells by approximately 40%. This and our inability to produce a viable TgAMA1 knock-out mutant indicate that this phylogenetically conserved protein fulfills a key function in the invasion of host cells by extracellular T. gondii tachyzoites.

Amino Acid Sequence↗