Microfilariae identified in FNA of a thyroid nodule.

A patient presented with hyperthyroidism and a thyroid swelling, clinically thought to be malignant. Fine-needle aspiration of the thyroid nodule revealed microfilariae of Wuchereria bancrofti. After therapy the thyroid swelling subsided and the patient became euthyroid. The possible etiologic role of microfilariae in the genesis of the thyroid tumor and hyperthyroidism is discussed.

Immunotechnological trends in radioimmunotargeting: from 'magic bullet' to 'smart bomb'.

The impact of recent advances in the chemical and genetic engineering manipulations of antibodies on radioimmunotargeting is reviewed both in relation to radioimmunoscintigraphy and radioimmunotherapy. The resulting trends are: (1) the linking of parts of the mouse/rat and human antibody molecule; (2) the creation of molecules with dual antigen or multiple antigen recognition capabilities; (3) the making of smaller and smaller antigen recognition molecules; and (4) the development of molecules with dual capabilities, e.g. antigen recognition and enzyme activity. The various methods of creating antibodies in vitro are reviewed with reference to bacteria, using phage selection and a combinatorial library, mammalian cells, yeast cells and, finally, mice containing giant yeast artificial chromosomes. The advantages and disadvantages of smaller fragments as well as of the human anti-mouse antibody (HAMA) reaction are discussed and the need for early clinical evaluation and widespread availability of the newer antibodies is emphasized. It is envisaged that these immunotechnological advances will permit the large-scale production of precisely engineered humanized antibodies, and the specificity and affinity rate constant of these antibodies can be optimized using in vitro phage selection as well as by computer modelling where the stereo chemistry of the antigen is known precisely.

Linking radiosilver to monoclonal antibodies reduced by ascorbic acid. Comparison of results with stable silver using gravimetric technique and silver 110-M using radiotracer technique.

Radiosilver-111 and Radiogold-199 were proposed by us (1) as suitable isotopes for radioimmunotherapy in areas such as India by reason of their suitable half-lives and B-emissions (Ag-111 T1/2 = 7.45 d and Au-199 T1/2 = 3.15 d). Since silver is monovalent, it is difficult to link to conventional bifunctional chelates. We therefore explored the use of sulfur-based linkers (2). Encouraged by the Thakur and De Fulvio Technique (3) of linking technetium to disulfide groups in antibodies reduced by ascorbic acid that is eminently biocompatible, we have explored the linkage of silver to immunoglobulin reduced by ascorbic acid. The linkage of silver was assessed with stable Ag-108 using dialysis to quantify the free silver after the reaction of silver and reduced immunoglobulins in various molar ratios (1:1, 1:2, 1:5, 1:10). The silver quantity was estimated gravimetrically after precipitation as chloride. It was observed that using these molar ratios there was negligible silver efflux into the dialysate, suggesting stable linkage. We also assessed the linkage using Ag-110M as radiotracer. The comparative results with the two techniques are described.

Removal of endotoxin from antibody preparations for clinical use. Assessment of polymyxin-sepharose CNBr affinity chromatography.

Despite attempts to maintain asepsis, good manufacturing practices, and the use of terminal sterilization by millipore filtration, the nuclear practitioner is always worried about the possibility of endotoxin contamination. Methods, such as ion-exchange chromatography, have been tried for removing endotoxins during the preparation of radiolabeled antibodies, and so on. As suggested by Stevenson (1990), we evaluated the Issekutz technique (1) of endotoxin removal by affinity chromatography using a polymyxin cyanogen bromide (CNBr) Sepharose column. The endotoxin content of millipore filtrates of heat killed/sonicated suspensions of Pseudomonas pyocyaneus, E. coli were measured using a Sigma (St. Louis, MO) Endotoxin Assay Kit before and after filtration through such columns and compared with the results obtained using gel exclusion and ion-exchange columns of the same length and diameter. Reduction of endotoxin content to undetectable levels by the polymyxin column was observed. The use of such columns for terminal endotoxin removal analogous to terminal sterilization is advocated especially when developing a radiopharmaceutical such as radiolabeled antibodies for in house use.

The significance of serum magnesium in diabetes mellitus.

The mean serum magnesium level in normal individual was found 1.967 +/- mgm/dl. No significant difference in serum magnesium level was found in various age groups. All diabetic patients, having normal renal function, exhibited hypomagnesemia. The hyperglycemia in these cases was inversely related to hypomagnesemia and its restoration towards normal by insulin therapy restored the normal serum magnesium concentration. These existed in inverse correlationship between serum magnesium and cholesterol (r = -0.56). The hypomagnesemia was the result and not the cause of alterations in the cholesterol metabolism. A positive correlation was observed between blood urea level and serum magnesium (r = +0.7) and it was significant. The magnesium correlated with major diabetic complications too, e.g. micro and macroangiopathies. Thus, serum magnesium can be used for prognostic assessment in diabetic individuals.

In vivo tuberculoma creation and its radioimmunoimaging.

Since tubercular lesions form an important differential diagnosis in our country, tuberculoma models in mice have been created and imaged using iodine-125 radiolabelled antimycobacterial monoclonal antibodies for the aetiopathological diagnosis.

Histomorphologic evidence of fracture healing after direct electrical stimulation in dogs.

A histomorphologic study was done at intervals up to 10 days after causing a fracture in both hindleg tibiae in dogs and giving direct electrical stimulation in one tibia, the other being used as control (20 microns ampere of direct current were passed in 28 limbs and the current was maintained with the help of a simple regulator developed by the authors). The radiologic and histomorphologic study showed definite evidence of early start and completion of healing processes in the electrically stimulated hindlegs. Negative potentials induced at the fracture sites appeared to be the cause of improved healing. The incidence of infection and focal necrosis at the anode was minimal in this experiment.