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Biomedical subjects

T E Hilditch

Publications and source records attributed to T E Hilditch.

At least 37 records · Page 2Linked to original sources

The design and construction of a central radiopharmacy.

Following an inspection by the Medicines Control Agency (MCA) of the existing radiopharmacy, it was necessary to design and build a new facility at the Western Infirmary to supply radiopharmaceuticals for patient use throughout the West of Scotland. This is one of the largest radiopharmacies in Europe, supplying some 40,000 patient doses per year prepared using both closed and open procedures. The design parameters and construction details of the new facility are presented.

Facility Design and Construction↗

Radiological protection guidance for radioactive patients--new data for therapeutic 131I.

Patients leaving hospital after 131I treatment for thyrotoxicosis face restrictions on their contact with other members of the public. These restrictions depend on the level of residual body radioactivity which for practical purposes can be taken to be almost entirely in the thyroid gland. This study provides an appropriate data base from which to draw advice to patients consistent with current radiological protection requirements in terms of the duration of these restrictions. Thyroidal retention of 131I was measured in 77 thyrotoxic patients over a period of 1-50 days after a first therapeutic administration of the radionuclide. Mean 131I activity in the gland (+/- S.D.) at 1 day was 56.1 +/- 11.1% of the administered dose activity and thereafter retention followed a single exponential decay pattern with a mean effective half-life (+/- S.E.M.) of 6.35 +/- 0.14 days. In patients who required further 131I therapy, there was evidence that retention could be markedly reduced if there was virtual ablation of thyroid tissue. It is proposed that these retention data can be used to determine body radioactivity at any interval after the administration of 131I for treatment of thyrotoxicosis, thus obviating the need for serial measurements in every individual patient.

Adult↗

Plasma gastrin, daytime intragastric pH, and nocturnal acid output before and at 1 and 7 months after eradication of Helicobacter pylori in duodenal ulcer subjects.

Nine patients with Helicobacter pylori-related antral gastritis and history of duodenal ulceration were studied before and at 1 and 7 months after eradication of the infection by a 4-week course of tripotassium dicitrato bismuthate, metronidazole, and amoxycillin. The median basal gastrin concentration before eradication was 30 ng/l (range, 20-60) and fell to 20 ng/l (5-20) at 1 month (p less than 0.02) and 15 ng/l (5-20) at 7 months (p less than 0.01) after eradication. The integrated gastrin response to a peptide meal was 3650 ng/l.min (range, 1875-6025) before treatment compared with 1800 ng/l.min (range, 1200-3075) at 1 month (p less than 0.01) and 1312 ng/l.min (875-2625) at 7 months (p less than 0.03). Daytime intragastric pH (0900-2100 h) was similar before treatment (median, 1.4; range, 1.1-2.1) and at 1 month (1.4; 1.1-2.3) and 7 months (1.4; 1-2.2) after eradication. In five of the patients nighttime acid output (2300-0900 h) was also studied and was similar before (median, 86 mmol/10 h; range, 52-114) and at 1 month (76 mmol/10 h; 50-143) and 7 months (94 mmol/10 h; 63-106) after eradication. In conclusion, eradication of H. pylori is accompanied by a sustained fall in serum gastrin concentrations but is not accompanied by an early or late reduction of daytime intragastric acidity or nighttime acid output.

Adult↗

Tumor spheroid model for the biologically targeted radiotherapy of neuroblastoma micrometastases.

Neuroblastoma is a pediatric malignancy with a poor prognosis at least partly attributable to an early pattern of dissemination. New approaches to treatment of micrometastases include targeted radiotherapy using radiolabeled antibodies or molecules which are taken up preferentially by tumor cells. Multicellular tumor spheroids (MTS) resemble micrometastases during the avascular phase of their development. A human neuroblastoma cell line (NBl-G) was grown as MTS and incubated briefly with a radiolabeled monoclonal antibody (131I-UJ13A) directed against neuroectodermal antigens. Spheroid response was evaluated in terms of regrowth delay or proportion sterilized. A dose-response relationship was demonstrated in terms of 131I activity or duration of incubation. Control experiments using unlabeled UJ13A, radiolabeled nonspecific antibody (T2.10), radiolabeled human serum albumin, and radiolabeled sodium iodide showed these to be relatively ineffective compared to 131I-UJ13A. The cell line NBl-G grown as MTS has also been found to preferentially accumulate the radiolabeled catecholamine precursor molecule m-[131I]iodobenzylguanidine compared to cell lines derived from other tumor types. NBl-G cells grown as MTS provide a promising laboratory model for targeted radiotherapy of neuroblastoma micrometastases using radiolabeled antibodies or m-iodobenzylguanidine.

Antibodies, Monoclonal↗

Fifteen years of radiological protection experience in a regional radiopharmacy.

Radiological protection experience in a regional radiopharmacy, currently handling 28.5 TBq (770 Ci) 99mTc y-1, is reviewed for the period 1974-1988. The results of personnel monitoring have shown a downward trend (by more than a factor of two) in radiation exposure of individual staff members, despite the workload per person [6000 GBq (162 Ci) 99mTc y-1] remaining virtually constant. Adequate staff selection and training contribute to the reduction in dose. A significant reduction in dose to the eyes was achieved by installing lead glass screens in the radiopharmacy work stations, and tungsten syringe shields reduced radiation dose to the hands. The use of commercially available kits for producing 99mTc radiopharmaceuticals, rather than relying on in-house preparations that require more operator handling, has also contributed to reduction in radiation exposure. Internal contamination of staff members with 125I was markedly reduced when the practice of sub-dispensing high-specific activity solutions of the radionuclide was discontinued. Annual doses from external radiation currently average less than 6 mSv (600 mrem) to the trunk, less than 7 mSv (700 mrem) to the eyes, and 50 mSv (5 rem) to the hands. Internal contamination of personnel with 125I, 131I, and 99mTc, as detected by thyroid and whole-body monitoring, contributed less than 65 mSv y-1 (6.5 rem) to the thyroid gland and less than 0.1 mSv y-1 (10 mrem) to the whole body.

Humans↗

Investigation of factors affecting adhesion of 99Tcm labelled colloids to glass vials.

Factors which may possibly influence the adhesion of 99Tcm labelled colloid to glass vials were investigated. Of five colloids studied, two protein-free tin colloids were affected most by the problem, some 12-18% being lost by adhesion to the glass vial when the colloid was left resting on the bench, or 60-87% when it was rotated for a period of 4 h. The proportion of activity which adhered to the vial was dependent on the time the product had been contained within it, whether on the bench or rotated. Two of the colloids, both of which contained protein, were affected only slightly by the problem, one being a tin colloid and the other a sulphur colloid. An antimony sulphide colloid, which contained no added protein, was virtually unaffected by the problem. The degree of adhesion was not related to the pH of the product, nor to the temperature at which the product was stored, nor to the tendency of the colloid particles to grow in size upon vigorous agitation.

Colloids↗

Effect of simulated intragastric haemorrhage on gastric acid secretion, gastric motility, and serum gastrin.

The majority of upper gastrointestinal bleeds stop spontaneously despite the low pH and proteolytic activity of gastric juice which inhibit coagulation and platelet aggregation. In order to investigate this paradox six healthy male volunteers received intragastric infusions of 160 ml autologous venous blood or 160 ml egg white acting as control in random order on separate days. Basal acid output was calculated before infusion, net acid secretion and gastric volume emptied were calculated after intragastric infusions. Serum gastrin concentrations were also measured before and after intragastric infusions and expressed as the integrated gastrin response. Basal acid output (mmol/h) was 4.7 (1.9) (mean (SEM)) before egg white infusion and 5.9 (2.6) before venous blood infusion. After egg white infusion net acid secretion (mmol/20 min) increased to 5.6 (3.1) compared with 2.3 (1.3) after venous blood infusion (p less than 0.05). The gastric volume emptied (ml/20 min) was less after venous blood infusion at 105 (28) compared with 321 (66) after egg white infusion (p less than 0.03). Integrated gastrin response was similar after venous blood and egg white infusion. When compared with an equivalent protein meal intragastric blood stimulates less acid secretion and delays gastric emptying. This effect may facilitate haemostasis after gastric bleeding.

Adult↗

Strategies for systemic radiotherapy of micrometastases using antibody-targeted 131I.

A simple analysis is developed to evaluate the likely effectiveness of treatment of micrometastases by antibody-targeted 131I. Account is taken of the low levels of tumour uptake of antibody-conjugated 131I presently achievable and of the "energy wastage" in targeting microscopic tumours with a radionuclide whose disintegration energy is widely dissipated. The analysis shows that only modest doses can be delivered to micrometastases when total body dose is restricted to levels which allow recovery of bone marrow. Much higher doses could be delivered to micrometastases when bone marrow rescue is used. A rationale is presented for targeted systemic radiotherapy used in combination with external beam total body irradiation (TBI) and bone marrow rescue. This has some practical advantages. The effect of the targeted component is to impose a biological non-uniformity on the total body dose distribution with regions of high tumour cell density receiving higher doses. Where targeting results in high doses to particular normal organs (e.g. liver, kidney) the total dose to these organs could be kept within tolerable limits by appropriate shielding of the external beam radiation component of the treatment. Greater levels of tumour cell kill should be achievable by the combination regime without any increase in normal tissue damage over that inflicted by conventional TBI. The predicted superiority of the combination regime is especially marked for tumours just below the threshold for detectability (e.g. approximately 1 mm-1 cm diameter). This approach has the advantage that targeted radiotherapy provides only a proportion of the total body dose, most of which is given by a familiar technique. The proportion of dose given by the targeted component could be increased as experience is gained. The predicted superiority of the combination strategy should be experimentally testable using laboratory animals. Clinical applications should be cautiously approached, with due regard to the limitations of the theoretical analysis.

Antibodies, Monoclonal↗

A tumour spheroid model for antibody-targeted therapy of micrometastases.

Human neuroblastoma cells grown as tumour spheroids were briefly incubated with a conjugate of 131I and an anti-human neuroectodermal monoclonal antibody UJ13A. Unbound 131I was removed by washing and the spheroids observed in culture conditions for up to 4 weeks. Spheroid response to irradiation was evaluated as time to reach 10x treatment volume and proportion of spheroids sterilised. Spheroid growth was found to be affected by both the activity of 131I-UJ13A and the duration of the incubation. Na[131I], 131I-HSA, 131I labelled non-specific antibody and unlabelled antibody were found to be relatively ineffective compared to 131I-UJ13A. The tumour spheroid model has applications in the evaluation of antibodies or antibody fragments and different radionuclides which may be considered for radioimmunotherapy of micrometastases.

Antibodies, Monoclonal↗

Automated radiopharmaceutical dispensing.

An automated workstation, developed for clinical biochemistry, has been evaluated for potential use in preparing radiopharmaceuticals. It was found that substantial modifications, both hardware and software, would be required but the approach seemed feasible.

Equipment Design↗

Bleeding colonic varices controlled by propranolol.

A 64-year-old man with hepatic cirrhosis developed severe haemorrhage from oesophageal varices. He underwent a course of sclerotherapy injections which successfully obliterated the oesophageal varices and prevented further oesophageal bleeding. He later developed serious bleeding from a site in the region of the ascending colon; angiography and radionuclide imaging suggested that varices were present in that region. Therapy with oral propranolol was effective in preventing any recurrence of gastrointestinal bleeding.

Colonic Diseases↗

Nonistropic point spread function as a result of collimator design and manufacturing defects.

A point spread function (PSF) which was of an unusual form was observed when using a low energy collimator and a 99mTc point source. A lack of radial symmetry and the detection of events over 20 cm away from the center of the source were noted. The major quantitative effect of this was a variation in the resolution of the system with direction. The consequences of this are likely to be of importance especially for single photon emission computed tomographic (SPECT) imaging. The effect was produced by a combination of faults in the design and manufacture of the low energy collimators. It demonstrates the importance of making quantitative measurements of collimator performance in the quality control assessment of gamma camera systems. For SPECT imaging the replacement of lead foil collimators with cast collimators should be considered.

Equipment Design↗

Digital filtering of the bladder in SPECT bone studies of the pelvis.

A data processing technique for the removal of bladder activity from single photon emission computed tomographic bone studies of the pelvis has been developed. The method involves the replacement of count values in the bladder on all projection views by data which are representative of the activity in surrounding structures. Reconstruction is then performed using the amended set of projection views. The method was tested by examining a group of 13 patients referred for investigation of avascular necrosis of the femoral head. Significant improvements in image quality were observed, particularly with respect to the level of artifact production, which increased the number of cases in which a confident and correct diagnosis was made.

Femur Head Necrosis↗