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D Ash

Publications and source records attributed to D Ash.

At least 19 recordsLinked to original sources

Potential disadvantages of post-operative adjuvant radiotherapy after anterior resection for rectal cancer: a pilot study of sphincter function, rectal capacity and clinical outcome.

The aim of this study was to try to gauge the functional effect of post-operative adjuvant radiotherapy after potentially curative anterior resection for carcinoma of the rectum. Anorectal function was studied both in the laboratory and clinically in 59 patients, a median of 12 months (range 6-96) after operation. Nine patients received post-operative radiotherapy and 50 matched patients were treated by surgery alone. Though maximum resting anal pressures and maximum squeeze pressures were similar in the two groups of patients, the length and pressure profile of the anal sphincter were both markedly abnormal after radiotherapy. The capacity and compliance of the neorectum were diminished significantly after radiotherapy (maximum tolerated volume 53 ml vs 110 ml after surgery alone, P = 0.008, compliance 1.5 ml/cm H2O vs 3.7 ml/cm H2O after surgery alone, p = 0.018) and the amount of distension of the neorectum required to produced maximum inhibition of the anal sphincter during the rectoanal inhibitory reflex was also significantly diminished after radiotherapy (P = 0.005). Clinical anorectal function was worse among patients who had received radiotherapy, a greater proportion of whom experienced both urgency of defaecation and varying degrees of incontinence. Major faecal leakage necessitating the use of a pad was recorded in 3 of the 59 patients after radiotherapy (one of whom required a permanent colostomy), but in only 5 of 50 patients after surgery alone.

Adult

Split course radiotherapy for bladder cancer in elderly unfit patients.

Between 1980 and 1987, 89 patients with T1-T4 carcinoma of the bladder were treated with a split course of external beam radiotherapy. All patients were felt to be unsuitable for a prolonged course of radical radiotherapy because of age and/or poor general health. The intention was to provide local control. The majority of patients were treated with 10-12 fractions, with a mean dose of 45 Gy (range 31.5-57.7), within a mean overall time of 48 days. Of the 89 patients only 62 were assessable with a median follow-up of 110 months (range 64-157). In the remainder, poor health, poor performance status, or early (< 3 months) death did not allow assessment of tumour control. Complete remission was achieved in 28/89 (31%) patients. This was highly dependent on T stage: 56% T1/T2, 30% T3a/T3b, 5% T4. Median survival for patients with Stage T1/T2, T3a/T3b and T4 disease was 22, 10 and 8 months respectively. Acute grade 1-2 radiation reactions occurred in 60% of these patients, and only 5/62 (8%) experienced grade 2-3 late complications, assessed according to the RTOG scoring system. No patient had more severe treatment related morbidity.

Adult

Report on the clinical effects of inadvertent radiation underdosage in 1045 patients.

Between Autumn 1982 and Winter 1991, 1045 patients received lower doses of radiation than were prescribed for the treatment of their cancers because of a miscalculation of radiation doses. This occurred as a result of the introduction of a new technique of treatment planning. An error in the application of the planning system lead to an underdosage of radiation of between 5 and 35%. In patients who received radiation alone for radical treatment a dose reduction of 20% or more resulted in a lower than expected local control rate. The effects were less marked in patients who were treated by combinations of surgery and radiation and in those with a very high rate of distant metastases. In 1991, a new computer planning system was installed and a discrepancy was discovered between the new plans and those from the previous system. Further investigation revealed that the original planning system already contained within it a correction factor for the tumour to skin distance and that systematically reapplying this correction had resulted in underdoses of radiation being delivered to patients for nearly 10 years. During the 9-year period of this dose miscalculation only 6% of patients treated in the department were treated with the isocentric technique; for many of those it formed only a part of their treatment.

Adolescent

The use of discriminant analysis to guide palliative treatment for lung cancer patients.

The aim of this study was to develop a prognostic index for patients with inoperable non-small cell lung cancer which could predict survival to 3 months. This would enable less radiation dose to be given to patients where prognosis is limited by occult metastases, giving rise to less treatment morbidity and raising the therapeutic ratio. Data on 18 known prognostic factors were collected on 96 patients. Performance status, lymphocyte count, weight loss and extent of disease were the most predictive factors and were combined into an index. Logistic discriminant analysis was employed to give a numerical score of likelihood of survival to 3 months, ranging from 0 (not likely) to 1 (certain). In this first set of 96 patients, 16 deaths were observed before 3 months, of which 6 were predicted. There was one false positive prediction. Overall accuracy of prediction was therefore 89% with 99% specificity. The same 4 prognostic factors were measured on a second set of 80 patients. Nineteen died before 3 months, of which 5 were predicted with 2 false positives, giving an overall accuracy of 80% and 97% specificity. A probability of survival of less than or equal to 0.2, although highly specific, was only applicable to 9% of patients and this was the limiting factor in the clinical usefulness of the test. A 16-branch tree diagram allows any patient to be assigned a risk factor based on the four predictive factors at the first clinic attendance. Use of the index could encourage more rational prescribing of radiation dose.

Activities of Daily Living

Therapeutic ratio of photodynamic therapy in the treatment of superficial tumours of skin and subcutaneous tissues in man.

Six patients with a total of 34 assessible subcutaneous or cutaneous lesions were treated with photodynamic therapy using 1.0, 1.5 or 2.0 mg kg-1 of photofrin II and 25-100 J cm-2 of red light (630 nm). The incidence of complete tumour response and skin necrosis were used to try to assess the therapeutic ratio of photodynamic therapy. The tumour response rate was 47%. The rate of tumour control and necrosis increased in parallel with dose of photosensitizer and light used, implying a low therapeutic ratio. However, the use of necrosis with eschar formation as an end-point for severe normal tissue damage is questioned as the skin healed completely in all cases and with minimal discomfort to the patients.

Dihematoporphyrin Ether

Prosthodontists' preferences in preprosthetic surgery.

A survey of members of the Federation of Prosthodontic Organizations was done to determine their opinions about various preprosthetic surgical procedures used to treat patients with alveolar atrophy of the maxilla and mandible. In most instances there was lack of consensus, indicating a need for consultation and close cooperation between the oral and maxillofacial surgeon and the prosthodontist in the management of individual patients.

Alveolar Ridge Augmentation

Problems associated with iridium-192 wire implants.

Three incidents are reported, from different radiotherapy centres, in which an implanted iridium-192 wire remained in the tissues of a patient after withdrawal of the plastic tubing in which it was contained. In each case the instrument used to cut the wire had probably formed a hook on the end of the wire which caused it to catch in the tissues. Detailed recommendations are made for avoiding such incidents in the future, the most important of which is that the patient should be effectively monitored after the supposed removal of all radioactive sources.

Aged

Whooping cough.

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Diphtheria Toxoid

Aliphatic ketones are acetylcholinesterase inhibitors but not transition state analogs.

A number of C4--C9 aliphatic ketones are acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) inhibitors, with Ki values in the 0.7--5 mM range. Comparison to analogous substrates would suggest that these ketones are transition state analogs; e.g. 2-pentanone binds to the enzyme approx. 550 times more tightly than ethylacetate. However, a number of other criteria contradict this conclusions: (1) the binding is insensitive to ketone structure: isomeric ketones, cycloalkanones, and sterically hindered ketones have similar inhibitory potencies. (2) Analogous alcohols are also good inhibitors even though they cannot form hemiketals with the enzyme. (3) Representative ketones are relatively ineffective at blocking inactivation of the enzyme by methylsulfonyl fluoride, indicating that ketones do not bind principally at the hydrolytic site. (4) A competition experiment shows that binding of tetramethylammonium chloride excludes binding of 2-pentanone, suggesting that ketones bind to the anionic rather than the hydrolytic site. Thus, observation of tight binding relative to a substrate is not a sufficient criterion to establish that an inhibitor is a transition state analog.

Animals

The Paris system in interstitial radiation therapy.

As a result of almost 20 years' experience using 192Ir wires in interstitial radiation therapy, a new method of dose calculation has been evolved, which is especially suitable for the techniques employed. Because this system was developed and brought into routine use in Paris, it was called the Paris System. Its basic principles are outlined in this report and the manner in which it is used in clinical practise is explained.

Breast Neoplasms

The mode of binding of potential transition-state analogs to acetylcholinesterase.

Phenylacetone, 4-phenyl-2-butanone, and 4-oxopentyltrimethylammonium chloride were tested as potential transition state analogs for eel acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7). Phenylacetone is a competitive inhibitor of the enzyme but not a transition state analog, since its binding constant is similar to that for the substrate phenyl acetate. 4-Phenyl-2-butanone binds 6-18 times more tightly than the inhibitors 4-phenyl-2-butanol and N-benzylacetamide and the substrate benzyl acetate and also blocks inactivation of the enzyme with methanesulfonyl fluoride. However, its binding is independent of pH in the range 5-7.5, whereas both V and V/Km for benzyl acetate hydrolysis decrease with decreasing pH in this range. These data indicate a specific but weak interaction between the ketone carbonyl and the enzyme, but probably do not justify considering this compound a transition state analog. 4-oxopentyltrimethylammonium iodide has previously been shown to bind about 125 times more strongly than the substrate acetylcholamine. It also binds about 375 times more strongly than the alcohol 4-hydroxypentyltrimethylammonium iodide. Furthermore, the ketone protects the enzyme from inactivation by methansulfony fluoride, while the corresponding quaternary ammonium alcohol accelerates this inactivation reaction. This additional information confirms that the ketone is a transition state analog.

Acetone