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Biomedical subjects

R B Richardson

Publications and source records attributed to R B Richardson.

At least 37 records · Page 2Linked to original sources

Dosimetry of intrathecal iodine131 monoclonal antibody in cases of neoplastic meningitis.

Radioiodinated monoclonal antibodies (MCA) were administered by the lumbar route into the cerebrospinal fluid (CSF) of four patients with malignant leptomeningeal disease. Evidence suggesting uptake of 131I-MCA by tumour sites was seen in scintigrams. Dosimetry calculations were carried out, assuming that a proportion of the administered radionuclide was bound as a thin layer on the CSF surfaces of the meninges. The percentage injected dose and the clearance curves for the head and four spinal segments were obtained by scintigraphy after administration of tracer amounts of 131I-MCA (7-18 MBq). Although radioisotope levels in the central nervous system (CNS) fell, as determined by both external scintillation counting and direct CSF sampling, a marked difference in the measurements developed with respect to time. The ratio of these two measurements reached a maximum of 49:1, 7 days after monoclonal antibody administration. Patients subsequently received therapeutic amounts (870-1600 MBq) of 131I-MCAs, resulting in clinical remissions and prolonged survival. The mean absorbed radiation dose was estimated as 3.9 cGy.MBq-1 to the thoraco-lumbar region of the spine and 0.51 cGy.MBq-1 to the outer surface of the brain. The maximal dose delivered to the surface of the CNS in the region of the spine and brain was 5800 and 600 cGy, respectively.

Adult↗

Intrathecal administration of 131I radiolabelled monoclonal antibody as a treatment for neoplastic meningitis.

Fifteen patients with neoplastic meningitis received a single intrathecal injection of between 11 and 60 mCi of a 131I radiolabelled monoclonal antibody (MoAb), chosen for its immunoreactivity to tumour. Major toxicity was manifest as nausea, vomiting and headache (7/15 patients), reversible bone marrow suppression (3/8 patients) and seizures (2/15 patients). Nine patients were evaluable for either a tumour or clinical response. Six of these demonstrated an event-free response that was maintained for periods of between 7 and 26 months.

Antibodies, Monoclonal↗

Assigning race to occupational cohorts using census block statistics.

Race is an important determinant of disease frequency, yet the race of subjects in retrospective epidemiologic studies is frequently unknown. If addresses are available, the race of study subjects may be estimated from the racial composition of the blocks on which they have resided. Such information can be obtained from census block statistics for Standard Metropolitan Statistical Areas and, with the 1990 Census, probably for the entire United States. The authors assigned black race to persons on blocks with greater than 60% black residents and white race to those residing on blocks containing less than 40% blacks. The validity of the procedure was tested on 341 decedents of known race who resided at the time of death within the Detroit, Michigan, Standard Metropolitan Statistical Area. Thirteen individuals who lived on blocks with 40-60% blacks were excluded from analysis, as well as 18 others for whom racial composition of blocks could not be ascertained. In 293 (94%) of the remaining 310 persons, race assigned on the basis of census information agreed with race obtained from death certificates. This method should prove useful for assigning race to study subjects lacking racial identification.

Black or African American↗

Mortality of iron foundry workers: I. Overall findings.

A retrospective cohort mortality study was conducted among 8147 men and 627 women employed in a gray iron foundry for at least 6 months between 1950 and 1979. More than 1700 deaths occurred during a 35-year period of observation. Standardized mortality ratios (SMRs) for all causes were close to expected values based on the US general population as the standard. The mortality of nonwhite men was significantly increased for lung cancer (SMR 132) and ischemic heart disease (SMR 126). Other moderate, but nonsignificant excesses were noted among nonwhite men for cancers of the stomach, pancreas, and prostate, for diabetes mellitus and pulmonary emphysema, and among white men for cancers of the lung and stomach, gastric and duodenal ulcers, pulmonary emphysema, and suicide. Small mortality increases were observed in both racial groups for cerebrovascular disease. The lack of a trend with time since hire and duration of foundry employment suggests that lung cancer mortality may not be associated with exposure to the foundry environment. Utilizing indirect measures of smoking, it appears that virtually all excess lung cancer deaths among whites and at least some of the excess among nonwhites could be explained by smoking habits. Similarly, smoking may have been responsible for the mortality excesses from emphysema, cerebrovascular diseases, and ischemic heart disease.

Adult↗

A pilot study of 131I monoclonal antibodies in the therapy of leptomeningeal tumors.

A pilot study was performed to investigate the toxicity and therapeutic effect of radiolabeled antibody administered intrathecally in patients with leptomeningeal tumors. Five patients who failed conventional therapy received between 11 mCi and 40 mCi of radiolabeled antibody. The choice of antibody varied depending on the immunophenotype of the tumor. Therapy was well tolerated generally, with minimal acute toxicity. Four of five patients achieved an objective response to treatment that has been sustained for a period varying from 7 months to 2 years. No clinical signs of chronic toxicity have been observed in patients 1 and 2 years after therapy.

Adult↗

Neoplastic meningitis from a pineal tumour treated by antibody-guided irradiation via the intrathecal route.

A monoclonal antibody (UJ181.4) was labelled with 131I and given intrathecally to a patient who was critically ill with neoplastic meningitis due to a disseminated pineoblastoma. The target antigen had first been demonstrated on tumour cells by immunocytological testing of cerebrospinal fluid (CSF). As a preparation for therapy, a test dose of 131I-UJ181.4 antibody was given simultaneously with a control antibody labelled with 125I. Good evidence of in vivo immunolocalization was obtained by external gamma counting and by analysis of the radiolabels on centrifuged CSF cells. Specificity ratios of between 10:1 and 20:1 were obtained by these methods. A single relatively small therapeutic dose of 131-I (870 MBq) given by the intrathecal route, resulted in a marked clinical improvement and sustained remission for 22 months.

Antibodies, Monoclonal↗

Radioimmunolocalization of human brain tumours: biodistribution of radiolabelled monoclonal antibody UJ13A.

Monoclonal antibody UJ13A, radiolabelled with 131I, was intravenously administered to patients with primary brain tumours. The antigen recognised by UJ13A is present on most neuroectodermally derived tissue. The ratio of uptake in tumour to normal brain, assessed by scintigraphy, improved with time. Maximal tumour uptake occurred between 4 and 48 h. Dynamic and static scintigrams indicated some early sequestration of radiolabelled antibody by the liver. Tumours were surgically resected in seven patients at various intervals after antibody administration showing tissue to blood ratios increasing with time in all parts of the lesion (viable and necrotic tumour, cyst fluid), and in normal brain. The highest tissue to blood ratio in viable tumour was 5.1 at 16 days after injection. In tissues resected 2-3 days after injection there was relatively greater uptake in the viable tumour compared to necrotic tumour and cyst fluid. In contrast, tissues resected later (6-16 days) showed greater uptake in ischaemic tissue than viable tumour, suggesting diffusion was an important factor influencing tumour uptake. The amount of radioactivity per gram of tumour tissue was less than 0.005% of the injected dose. Future studies are needed using different antibodies, antibody fragments and additional methods of optimising delivery.

Antibodies, Monoclonal↗

Observations on dermal blood flow as reflected by technetium-99m pertechnetate clearance.

Skin blood flow as reflected by the clearance rate of intradermal injections of Technetium-99m (99mTc) was studied in the skin of human volunteers and in a variety of clinical situations. In volunteers comparisons between the effect on clearance following intradermal injections of either lignocaine or lignocaine/adrenaline showed that the latter resulted in a dramatic reduction in the clearance rate of the technetium isotope and that such clearance curves exhibited no fast component. Clinical studies in grossly ischaemic skin revealed a similar absence of the fast component of isotope clearance and this was also the case for healed split thickness skin grafts. The dermal isotope clearance was also used in pedicle skin flaps both before and after clamping the axial pedicle in order to derive clearance ratios which would reflect the degree of neovascularisation to the flap. These preliminary observations suggest that the technique is safe, and easy to use in many clinical circumstances. We consider that it offers a valuable method by which changes in dermal blood flow may be quantified, when simultaneous control areas of isotope clearance are also studied. Suggestions are made for further avenues of study.

Adult↗

Influence of knowledge of peak flow on self assessment of asthma: studies with a coded peak flow meter.

A portable peak flow meter based on a turbine transducer that can display results in code has been developed. Its performance compares well with the Wright peak flow meter. Records of subjective self assessment of asthma on a visual analogue scale and of peak flow (PEF) were compared in 12 subjects with asthma. PEF measurements were made with a coded meter for two weeks and an uncoded meter for two weeks in random order. The correlation between visual analogue scale score and PEF was invariably stronger when PEF was known. Changes in perception of asthma were measured by comparing the slopes and relative positions of the regressions of visual analogue on PEF. When PEF was uncoded awareness of asthma was significantly increased in five patients, predominantly those whose perception was poorest while they were using the coded meter, and decreased in only one patient. In two patients the results were unsuitable for this type of analysis. Knowledge of PEF therefore may influence subjective self assessment in patients with bronchial asthma. For objective studies of symptoms of asthma, PEF readings should be unknown to the patient. Perception of asthma may, however, be improved in patients with poor ability to detect changes in bronchial calibre by uncoded measurement of peak flow at home.

Adult↗

Compartmental analysis of cerebrospinal fluid transfer and absorption in simulated hydrocephalus.

A mathematical model of the cerebrospinal fluid (CSF) flow dynamics found in hydrocephalic infants with myelomeningocele lesions was constructed using criteria obtained from analogous clinical situations where 125I-labelled and 131I-labelled ortho-iodobenzoyl-amino-acetic acid (hippuran) had been employed to measure CSF flow dynamics. The quantitative results from this study allowed clinical data to be assessed and the importance of various CSF transfer mechanisms to be discussed. Our mathematical model indicates that the majority of radiopharmaceutical passes from the cerebral reservoir (the ventricles) into the blood. Experimental evidence indicates that the principal mechanism responsible for this movement is the bulk flow of CSF between its sites of production in the choroid plexus and absorption by the arachnoid villi.

Blood-Brain Barrier↗

An evaluation of the Meditech M250 and a comparison with other CT scanners.

The Meditech M250 computerised tomography (CT) machine was evaluated during the first half of 1984. Measurements were made of noise, modulation transfer function, slice width, radiation dose profile, uniformity and linearity of CT number, effective photon energy and parameters relating to machine specification, such as pixel size and scan time. All breakdowns were logged to indicate machine reliability. A comparison with the established EMI CT1010 and CT5005 was made for noise, resolution and multislice radiation dose, as well as the dose efficiency or quality (Q) factor for both head and body modes of operation. The M250 was found to perform to its intended specification with an acceptable level of reliability.

Equipment Design↗

An electronic peak flow meter with optional coded display.

A portable electronic spirometer giving peak expiratory flow rate has been developed and used successfully in studies of asthma. A turbine flow transducer produces a pulsed output whose frequency is proportional to flow. The output was coded to keep the results 'blind' to the patient. The code is suitable for use on other electronic instruments employing a similar display. It has been successfully used to investigate patients' perception of their asthma.

Asthma↗

The effect of regular inhaled salbutamol on the airway responsiveness of normal subjects.

1. Airway responses to inhaled salbutamol were measured in two groups of six normal non-atopic subjects. In each group there was a dose-dependent increase in specific airways conductance after salbutamol inhaled in cumulative doses from 25 to 600 micrograms. 2. In the first group these studies were repeated weekly during and after the subjects had taken regular inhaled salbutamol for 4 weeks, in doses increasing to 500 micrograms four times daily by week 5. Then, while subjects were continuing to receive regular salbutamol, the studies were repeated after 48 h of inhaled sodium cromoglycate (20 mg four times daily) and again after 48 h of beclomethasone dipropionate (200 micrograms four times daily). 3. In the second group the studies were repeated after 10 days of regular inhaled salbutamol (500 micrograms four times daily). 4. There was no change in airway response to inhaled salbutamol after 4 weeks or 10 days regular salbutamol therapy, or after 48 h of sodium cromoglycate or beclomethasone dipropionate therapy. 5. This study did not show the development of resistance to beta-agonists in the airways of normal subjects. These findings are discussed in the context of other studies which have shown the development of resistance, and we suggest that there may be a spectrum of susceptibility to the development of impaired airway responsiveness following regular treatment with beta-adrenergic drugs.

Adolescent↗

Pupillary fatigue in myasthenia gravis.

By shining a narrow beam of light upon the pupillary margin, a sustained oscillation of pupil size or hippus, may be induced; the frequency of which is dependent upon the rate of conduction along the neuronal pathways subserving pupillary function. This manoeuvre has been carried out upon a series of twelve patients with myasthenia gravis, eleven of whom demonstrated a gradual diminution in oscillation frequency. This is compared with twelve control subjects, only one of whom demonstrated a significant decline in oscillation rate. The mean gradients were 0.0 +/- 0.4 cycles/min for the control subjects and -2.4 +/- 0.4 cycles/min for the patients with myasthenia. These gradients differ significantly p less than 0.0001. It is suggested that the pupillary reaction to light may be fatigued by exercising it at its maximum intrinsic rate in patients with myasthenia gravis.

Adult↗