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M N Gaze

Publications and source records attributed to M N Gaze.

47 records · Page 3Linked to original sources
PubMed1991

Intracellular localization of metaiodobenzyl guanidine in human neuroblastoma cells by electron spectroscopic imaging.

The targeted radiotherapy of neuroblastoma with 131l-labelled metaiodobenzyl guanidine (mIBG) is now the subject of several clinical studies. The precise intracellular localization of mIBG, necessary for nuclear microdosimetry, has not previously been described. We report the use of electron-energy-loss spectroscopy and electron spectroscopic imaging to establish the intracellular distribution of mIBG in cells from the human neuroblastoma line NBI-G which had been incubated with the drug by mapping iodine in ultra-thin sections of tumours. Most of the iodine is found within the mitochondria, with lesser amounts in the vesicles and on the nuclear membrane. The use of alternative radionuclides with different physical characteristics has been suggested to optimize the efficacy of this therapeutic strategy. The lack of penetration of mIBG into the nucleoplasm means that ultra-short-range Auger electron emitters such as 125I are not likely to prove more cytotoxic than 131I.

3-Iodobenzylguanidine↗
PubMed1991

The effect of laryngeal irradiation on pharyngoesophageal motility.

The upper esophageal sphincter (UES) receives the full radiation dose during external beam radiotherapy to the adjacent larynx. The aim of the study was to assess the effects, if any, of radical laryngeal radiotherapy on motility patterns in the pharyngoesophageal segment. A strain gauge assembly and a digital manometric recorder were used to assess 19 patients 13 to 71 months after irradiation of T1 to T3 glottic cancer to a central dose of 52.5 to 55.7 Gy in 20 daily fractions. Results were compared with those of 23 healthy controls. Tonic lower esophageal sphincter (LES) pressure, distal peristaltic contraction, tonic UES pressure, and eight parameters of pharyngoesophageal dynamics during water and bread swallows were studied. No difference was found between the two groups in tonic LES pressure, peristaltic amplitude, or tonic UES pressure. Water swallow pharyngoesophageal wave velocity was significantly lower in patients than in controls, and the irradiated group also showed a trend toward increased duration of the distal esophageal peristaltic wave. The reduction in upper esophageal wave velocity was associated with the interval following irradiation. The post-treatment interval was also inversely related to the amplitude of UES after-contraction, and associated with an increase in wave duration throughout the pharyngoesophageal segment. A study of 23 laryngectomy specimens, 5 of which had been removed following radiotherapy, failed to identify pathological features in nerves or muscle which characterised previous laryngopharyngeal irradiation. We conclude that laryngeal irradiation has no effect on upper or lower esophageal sphincter tone but causes an increase in wave duration and a reduction in wave velocity in the pharyngoesophageal segment. These changes are independent of age and sex and are not associated with pathological features like the neural degeneration described in the myenteric plexus of irradiated rectum.

Aged↗
PubMed1991

Bone scan hot spots in a patient with lung cancer: ischaemic necrosis of bone mimicking metastatic carcinoma.

A 62-year-old man complained of a pain in his leg four months after radical surgery for a bronchial adenocarcinoma. Skeletal scintigraphy showed increased uptake of isotope in the lower femur and upper tibia corresponding to an abnormal area on the plain radiographs. Bone metastases were thought to be the most likely cause of these findings. Since the appearances were not entirely typical, bone biopsy was undertaken to confirm the diagnosis. This showed ischaemic necrosis of bone, related to a previous acute arterial occlusion. In view of the serious implications for a patient if an erroneous diagnosis of metastatic disease is made following potentially curative treatment for cancer, such a diagnosis should be proven, not assumed. Bone biopsy should be considered when solitary skeletal lesions develop in radically treated cancer patients with no other evidence of metastasis.

Adenocarcinoma↗
PubMed1991

The distribution of alternative agents for targeted radiotherapy within human neuroblastoma spheroids.

This study aims to select the radiopharmaceutical vehicle for targeted radiotherapy of neuroblastoma which is most likely to penetrate readily the centre of micrometastases in vivo. The human neuroblastoma cell line NB1-G, grown as multicellular spheroids, provided an in vitro model for micrometastases. The radiopharmaceuticals studied were the catecholamine analogue metaiodobenzyl guanidine (mIBG), a specific neuroectodermal monoclonal antibody (UJ13A) and beta nerve growth factor (beta NGF). Following incubation of each drug with neuroblastoma spheroids, autoradiographs of frozen sections were prepared to demonstrate their relative distributions. mIBG and beta NGF were found to penetrate the centre of spheroids readily although the concentration of mIBG greatly exceeded that of beta NGF. In contrast, UJ13A was only bound peripherally. We conclude that mIBG is the best available vehicle for targeted radiotherapy of neuroblastoma cells with active uptake mechanisms for catecholamines. It is suggested that radionuclides with a shorter range of emissions than 131I may be conjugated to benzyl guanidine to constitute more effective targeting agents with potentially less toxicity to adjacent normal tissues.

3-Iodobenzylguanidine↗
PubMed1990

Mucosal melanomas of the head and neck: The Scottish experience. The Scottish Melanoma Group.

A retrospective analysis of malignant melanoma of the upper aerodigestive tract treated in Scotland between 1976 and 1988 has been performed to define the incidence, clinical features and response to treatment. Using the Scottish Melanoma Group database and pathology and oncology department registers 32 patients, 20 female, 12 male, were identified, representing a population incidence of approximately 0.5 per million per year. The median age was 69 years, range 38-86. Tumour arose in the nose or sinuses in 23 cases and the oral cavity or pharynx in eight cases. Metastases were present at presentation in four cases. Radical treatment was attempted in 27 patients: radiotherapy alone in 13, surgery alone in 10 and combined modality treatment in four. Complete regression, which was sustained in five cases, occurred in eight of the 13 radically irradiated patients; whereas sustained local control was achieved by radical surgery in only four of ten patients. The median survival is 14 months, non lived more than 63 months. Only one patient is alive and disease free, three more survive with disease. Of the 28 who had died, nine had local tumour only, nine metastases only and ten both local and distant disease. Outcome was not affected by age, sex, primary site or nodal spread.

Adult↗
PubMed1990

Mucosal immunodeficiency in smokers, and in patients with epithelial head and neck tumours.

Cigarette smoking influences the risk of orogastrointestinal disease in both protective (ulcerative colitis), and inductive (squamous tumours of the head, neck and oesophagus) roles. In order to study the effects of smoking on mucosal immunity, salivary immunoglobulins were measured in pure parotid saliva from groups of healthy non-smokers, smokers, and exsmokers and from patients with epithelial head and neck tumours, both untreated and after radiotherapy. Of the healthy individuals, smokers had significantly lower salivary IgA and higher IgM concentrations than did non-smokers. The effect on IgA was dose related, and reversible after cessation of smoking. Likewise, in patients with head and neck tumours (the majority being smokers), salivary IgA concentration was reduced and IgM increased when compared with non-smoking controls. Results were similar before and after radiotherapy. This study provides evidence of the effects of smoking on mucosal immunity as evaluated by parotid salivary immunoglobulins. Further studies of the influence of smoking on secretory immunity are indicated.

Adult↗
PubMed1989

Arm morbidity within a trial of mastectomy and either nodal sample with selective radiotherapy or axillary clearance.

The aim of this study was to assess upper limb morbidity following treatment for operable breast cancer. Patients were randomized to either mastectomy and axillary clearance (40 women: 12 with axillary nodal metastasis and 28 without axillary metastasis) or mastectomy and axillary sampling (54 women). Adjuvant radiotherapy was delivered to those in whom the sample revealed axillary nodal metastasis (28 women) but not to those with no axillary nodal metastasis (26 women). A subjective assessment of the state of the arm was made using a standard questionnaire. Objective assessment included upper and forearm circumference, should joint mobility and assessment of power in the pectoralis muscle. The mean age was 56.8 years (range 33-77 years) and the mean elapsed time from treatment was 5.72 years (range 4.0-7.5 years). Subjective limb oedema was greatest in those who had axillary lymph node metastasis but there was no objective difference. Subjective joint mobility was reduced in the women who received radiotherapy and this was confirmed by objective assessment (P less than 0.05). The objective reduction in arm mobility was related to the treatment rather than the axillary lymph node status. There was no difference in power. In this study women receiving adjuvant radiotherapy had significantly reduced shoulder mobility. This may have implications for current conservation studies using adjuvant radiotherapy.

Adult↗