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Biomedical subjects

A Armour

Publications and source records attributed to A Armour.

15 recordsLinked to original sources

Late radiation side-effects in three patients undergoing parotid irradiation for benign disease.

We report three patients in whom standard radiation therapy was given and serious late radiation damage was seen. The first patient suffered recurrent parotiditis and a parotid fistula. He was treated initially with 20 Gy in ten fractions via a 300 kV field. Further irradiation was required 1 year later and 40 Gy was given in 2 Gy fractions by an oblique anterior and posterior wedged photon pair. Ten years later he developed localized temporal bone necrosis. The second patient, with pleomorphic salivary adenoma, developed localized temporal bone necrosis 6 years after 60 Gy had been given using standard fractionation and technique. The third patient received 55 Gy in 25 fractions for a pleomorphic salivary adenoma and after 3 years developed temporal bone necrosis. Sixteen years later the same patient developed cerebellar and brainstem necrosis. All patients developed chronic persistent infection during or shortly after the radiation therapy, which increased local tissue sensitivity to late radiation damage. As a result, severe bone, cerebellar and brainstem necrosis was observed at doses that are normally considered safe. We therefore strongly recommend that any infection in a proposed irradiated area should be treated aggressively, with surgical debridement if necessary, before radiotherapy is administered, or that infection developing during or after irradiation is treated promptly.

Aged↗

Apoptosis in cervical squamous carcinoma: predictive value for survival following radiotherapy.

BACKGROUND: Apoptosis, or programmed cell death, can be induced by radiotherapy. The extent of apoptosis in a tumour before treatment may have important implications for response to radiotherapy and long term survival. AIM: To examine the extent of apoptosis in tumour tissue from patients with squamous carcinoma of the cervix before radiotherapy, and to correlate this with response to treatment and prognosis. METHODS: The percentage of apoptotic cells was assessed in 146 carcinomas of the cervix from patients scheduled to receive radiotherapy. The CAS 200 static image analysis system was used to count the number of tumour nuclei per high power field, while the numbers of apoptotic cells in the same field were visualised simultaneously on the image analyser and recorded manually. RESULTS: The median apoptotic level was 0.73%. Patients were divided into two groups around the median. There was no statistically significant difference in outcome between the two groups as determined by long term survival following radiotherapy. CONCLUSIONS: The CAS 200 static image analyser system can be used to assist in the rapid semiautomated assessment of apoptosis in conventionally prepared tissue. The results suggest that the apoptotic state of a tumour before treatment is of no value in predicting response to radiotherapy and subsequent prognosis. Tumour stage, size, and BrdU labelling index, as a measure of proliferation rate, remain the most important prognostic factors in terms of predicting local tumour control.

Analysis of Variance↗

The effect of cisplatin pretreatment on the accumulation of MIBG by neuroblastoma cells in vitro.

[131I]meta-iodobenzylguanidine ([131I]MIBG) provides a means of selectively delivering radiation to neuroblastoma cells and is a promising addition to the range of agents used to treat neuroblastoma. As MIBG is now being incorporated into multimodal approaches to therapy, important questions arise about the appropriate scheduling and sequencing of the various agents employed. As the ability of neuroblastoma cells to actively accumulate MIBG is crucial to the success of this therapy, the effect of chemotherapeutic agents on this uptake capacity needs to be investigated. We report here our initial findings on the effect of cisplatin pretreatment on the neuroblastoma cell line SK-N-BE (2c). After treating these cells with therapeutically relevant concentrations of cisplatin (2 microM and 20 microM), a stimulation in uptake of [131I]MIBG was observed. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that this effect was due to increased expression of the noradrenaline transporter. These results suggest that appropriate scheduling of cisplatin and [131I]MIBG may lead to an increase in tumour uptake of this radiopharmaceutical with consequent increases in radiation dose to the tumour.

3-Iodobenzylguanidine↗

Dilutional hyponatraemia: a cause of massive fatal intraoperative cerebral oedema in a child undergoing renal transplantation.

A four year old boy with polyuric renal failure resulting from recurrent urinary tract infections and vesicoureteric reflux from birth underwent renal transplantation. In the past he had had five ureteric reimplant operations and a gastrostomy, as he ate nothing by mouth. He required peritoneal dialysis 13 hours a night, six nights a week. His fluid requirements were 2100 ml per day. This included a night feed of 1.5 litres Nutrizon. Before operation he received 900 ml of Dioralyte instead of the Nutrizon feed, and peritoneal dialysis was performed as usual. The operation itself was technically difficult and there was more blood loss than anticipated, requiring intravenous fluids and blood. The operation ended about four hours later but he did not wake up. Urgent computed tomography revealed gross cerebral oedema. He died the next day. At necropsy the brain was massively oedematous and weighed 1680 g.

Brain Edema↗

Nosological Inaccuracies in death certification in Northern Ireland. A comparative study between hospital doctors and general practitioners.

We aimed to audit nosological inaccuracies in death certification in Northern Ireland and to compare performance of hospital doctors and general practitioners. Nosology is the branch of medicine which treats of the classification of disease. 1138 deaths were registered in Northern Ireland in a 4-week period commencing 3/10/94. 195 of these were either registered by HM Coroners (HMC) or required further investigation by their staff; these cases were excluded from the study. The remaining 943 were analysed for wording and formulation inaccuracies according to the revised notes (1974), Northern Ireland Medical Certificate of Cause of Death. These are issued in book form by the Registrar of Births and Deaths. The commonest inaccuracies in death certification occur in the areas of poor terminology, sequence errors and unqualified mode. One or more inaccuracies were found in 317 (33.6%) of cases. In 13 of these (4%) cases, the inaccuracies were serious enough to warrant referral by the Registrar of Deaths to HM Coroner. The numbers of general practitioners and hospital doctors were recorded, with general practitioners being responsible for 122 (38%) and hospital doctors being responsible for 195 (62%) of inaccuracies.

Cause of Death↗

No-carrier-added iodine-131-MIBG: evaluation of a therapeutic preparation.

UNLABELLED: Iodine-131-metaiodobenzylguanidine ([131I]MIBG) is a radiopharmaceutical for imaging as well as targeted radiotherapy of neuroblastoma. It is predicted that the use of no-carrier-added [131I]MIBG, rather than the conventional low specific activity preparation, will result in an enhanced therapeutic ratio because of different transport processes in neuroblastoma compared with most normal tissues. METHODS: The main aims of the study were: (1) to determine whether [131I]MIBG of substantially greater specific activity is transported into tumor cells by the same process as the existing compound; (2) to evaluate the effect of nonradiolabeled MIBG on the cytotoxicity of no-carrier-added [131I]MIBG; and (3) to compare the biodistribution of both preparations of the radiochemical in neuroblastoma xenografts. RESULTS: Active uptake of no-carrier-added [131I]MIBG was temperature-, sodium- and oxygen-dependent; ouabain- and desmethylimipramine-inhibitable; and could be blocked competitively by monoamine inhibitors of the noradrenaline transport mechanism. The rank order of specific uptake capacity in a panel of neuroblastoma cell lines was the same for both low and high specific activity drug. Neuroblastoma spheroid regrowth was 85% inhibited by no-carrier-added [131I]MIBG at 2 MBq.ml-1. Inhibitory potency was reduced in a dose-dependent manner by nonradiolabeled MIBG. The accumulation of no-carrier-added [131I]MIBG was significantly greater in tumor, adrenal, heart and skin of tumor-bearing mice than that of the conventional therapy preparation of [131I]MIBG. CONCLUSION: These data indicate that there may be clinical advantages in the use of no-carrier-added [131I]MIBG rather than conventional [131I]MIBG.

3-Iodobenzylguanidine↗

Modification of meta-iodobenzylguanidine uptake in neuroblastoma cells by elevated temperature.

Successful imaging or treatment of neuroblastoma with 131I-meta-iodobenzylguanidine (131I-mIBG) depends on the selectivity of active (type 1) uptake of mIBG in neuroblastoma cells relative to passive (type 2) uptake present in most normal tissues. This study investigates the effects of moderately elevated temperature (39-41 degrees C) on the cellular uptake of 131I-mIBG in two neuroblastoma cell lines [SK-N-BE(2c) and IMR-32] and in a non-neuronal (ovarian carcinoma) cell line (A2780). In SK-N-BE(2c), a cell line with high active uptake capacity, the specific (type 1) uptake was reduced by 75% (P < 0.001) at 39 degrees C. Both IMR-32 and A2780 have a low capacity for accumulation of mIBG by active uptake. These cell lines demonstrated a statistically significant increase in accumulation at 39 degrees C, mainly as a result of increased non-specific transport. At 41 degrees C uptake of 131I-mIBG was reduced in all cell lines. Thus, the active component of mIBG uptake is more vulnerable to increased temperature than the passive component. It seems probable that moderately increased temperature will have an unfavourable effect on the therapeutic differential for targeted radiotherapy of neuroblastoma using radiolabelled mIBG.

3-Iodobenzylguanidine↗

Ectopic cervical hamartomatous thymoma showing extensive myoid differentiation.

Ectopic 'hamartomatous' thymoma is a rare benign neoplasm. These tumours are found in the neck and are thought to be part of a spectrum of ectopic cervical thymic neoplasia. The clinical and histological features are discussed and the literature is reviewed. An attempt is made to explain in embryological terms why such lesions appear to occur more commonly on the left side.

Choristoma↗

Paracetamol cardiotoxicity.

A 29 year old man with a significant paracetamol overdose was found to have an abnormal electrocardiograph which, in the absence of hepatic encephalopathy, was considered due to a direct cardiotoxic effect of the drug. A functional coronary insufficiency resulting from inhibition of endothelium-derived relaxing factor secondary to depletion of sulphydryl groups is postulated, and it is suggested that in paracetamol poisoning evidence of cardiotoxicity alone may be sufficient justification for treatment with acetylcysteine.

Acetaminophen↗

A study of gunshot suicides in Northern Ireland from 1989 to 1993.

A study of 104 gunshot suicides, including six women, in Northern Ireland over a 5-year period. Forty-five suicides in the security forces are compared with 59 which took place in the civilian population. The former were commonly associated with marital problems and overwhelmingly occurred in young males under the age of 40, whereas the civilian deaths were predominantly associated with mental ill health, with a wider age range distribution. The security forces used rifled weapons in 44 cases, whereas civilians used shotguns in 46 cases. Twelve out of the 45 were witnessed, compared to one in the civilian population. The security forces favoured the head as site of entry in 40 cases compared to 35 in the civilian population. Alcohol consumption was involved in 23 of the security forces suicides and 18 civilian. Of the 6 women, one was in the security forces and 4 had a history of mental illness.

Adult↗