PubMed HealthSearch

Biomedical subjects

L Golberg

Publications and source records attributed to L Golberg.

At least 19 recordsLinked to original sources

Non-invasive assessment of human tumour hypoxia with 123I-iodoazomycin arabinoside: preliminary report of a clinical study.

Non-invasive predictive assays which can confirm the presence or absence of hypoxic cells in human tumours show promise for understanding the natural history of tumour oxygenation, and improving the selection of patient subsets for novel radiotherapeutic strategies. Sensitiser adducts have been proposed as markers for hypoxic cells. Misonidazole analogues radiolabelled with iodine-123 have been developed for the detection of tumour hypoxia using conventional nuclear medicine techniques. In this pilot study, we have investigated one such potential marker, 123I-iodoazomycin arabinoside (123I-IAZA). Patients with advanced malignancies have undergone planar and single-photon emission computed tomographic (SPECT) imaging after intravenous administration of 123I-IAZA. We have observed radiotracer avidity in three out of ten tumours studied to date. Normal tissue activity of variable extent was also seen in the thyroid and salivary glands, upper aerodigestive tract, liver, intestine, and urinary bladder. Quantitative analysis of those images showing radiotracer avidity revealed tumour/normal tissue (T/N) ratios of 2.3 (primary small cell lung carcinoma), 1.9 (primary malignant fibrous histiocytoma) and 3.2 (brain metastasis from small cell lung carcinoma) at 18-24 h post injection. These preliminary data suggest that the use of gamma-emitter labelled 2-nitroimidazoles as diagnostic radiopharmaceuticals is feasible and safe, and that metabolic binding of 123I-IAZA is observed in some, but not all tumours. The inference that tumour 123I-IAZA avidity could be a non-invasive measure of tumour hypoxia deserves independent confirmation with needle oximetry.

Adult

MAb 170H.82: an evaluation of a novel panadenocarcinoma monoclonal antibody labelled with 99Tcm and with 111In.

A novel method for generating monoclonal antibodies against synthetic tumour-associated glycoconjugates has been developed. One of these monoclonal antibodies, designated 170H.82, was derived against the TF antigen and has been shown in vitro to have a wide range of reactivity with adenocarcinoma. This antibody has been labelled with 111In and 99Tcm and has been evaluated in pilot clinical trials involving 48 patients with a range of adenocarcinoma. Overall clinical accuracy with the radiolabelled antibody was 92%, with the antibody appearing to have particular clinical utility in gynaecological and breast cancers. Single photon emission computed tomographic (SPECT) imaging was shown to improve the quality of the images and to improve the diagnostic sensitivity. We believe that this unique antibody, labelled with 99Tcm, appears to offer promise for routine clinical use in the evaluation of patients with a range of primary and metastatic adenocarcinoma.

Adenocarcinoma

Implications for human health.

To analyze the implications for human health, the toxicologist requires four sets of data: the results of toxicity and other studies in animals; quantitative data on actual or potential human exposure; whatever information is available on effects of exposure in man; and the statistical extrapolations from the dose-response relationships in animals to the (usually) much lower levels of human exposure. Professional expertise in toxicology is essential to assess the nature and severity of the toxic effects observed in animals, including such characteristics as potential for progression, irreversibility and production of incapacity. Given sufficient data, an estimate can be arrived at of the likelihood that such effects will be elicited in human populations of differing susceptibilities. The criteria by which the overall implications for human health can be judged comprise both the direct effects on man, as well as the indirect consequences stemming from environmental impacts.

Animals

Safety evaluation concepts.

The approach to safety evaluation is strongly influenced by the standard of safety to which one aspires. Practical considerations demand that realistic limits be set to the attainable assurances of freedom from anticipated hazard under actual conditions of use of a product. The fact is that, in the interests of consumer health, more can be expected from a flexible, intelligent, and experienced approach to safety evaluation than from efforts at conformity with a set of rigidly standardized requirements that are theoretically all-encompassing. Establishment of safety demands a wide background of information about the properties and likely uses of the product; above all, knowledge of the chemical composition of the product and its impurities, degradation products, and metabolites is essential. Lack of such information is a frequent source of errors in safety evaluation. Based on a secure foundation of this sort, a program of investigations may be designed, aimed at establishing the basic biological properties of the material. Determination of the metabolic dynamics of the principal chemical agent or agents makes possible the emergence of a clear picture of the behavior of the compound(s) in the body and paves the way for more specialized studies of long term toxicity, carcinogenicity, effects on reproduction and teratogenesis, and investigations of multitest mutagenic potential. Emphasis is laid on the problems of interpretation of results in terms of hazard to man and on the crucial contribution that experience of human exposure can make toward assuring safety-in-use. Decisions on acceptable risk are the joint responsibility of many individuals but an essential element in reaching such decisions is contributed by the depth of understanding and broad experiences of the toxicologist.

Accident Prevention

Chromatographic methods for the analysis of hexachlorobenzene and possible metabolites in monkey fecal samples.

The separation and identification of hexachlorobenzene (HCB), pentachlorobenzene (QCB), and pentachlorophenol (PCP) by thin layer, high-pressure liquid, and gas chromatography are reported. Satisfactory results were obtained with reverse phase thin layer and high-pressure liquid chromatography. The 2 gas chromatographic columns tested gave adequate separation of HCB and QCB. A PCP methylation process using dimethyl sulfate was attempted. Procedures are presented for extraction, cleanup, separation, and identification of HCB and possible metabolites from feces of a rhesus monkey treated with 14C-HCB. Recovery of radioactivity in excess of 96% was attained in extracts from feces by these methods. Preliminary evidence suggests the formation of PCP and possibly other polar metabolites from HCB in the rhesus monkey.

Animals