Jeno Szabo

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the differential diagnosis of cold thyroid nodules

Abstract. Various diagnostic techniques have been successfully used in the clinical management of cold nodules; however, the decision on whether to employ surgery or a conservative treatment is not always easy. This study was designed to appraise the diagnostic value of technetium-99m methoxyisobutylisonitrile (MIBI) scintigraphy in the assessment of cold nodules detected using 99mTc-pertechnetate. Fifty-two patients were included in the study. All had already been selected for surgery, based on their clinical and laboratory findings, including fine-needle aspiration biopsy. The total number of cold nodules on 99mTc-pertechnetate scans was 59. The thyroid scan was performed 20-40 min after i.v. injection of 400 MBq of 99mTc-MIBI. Uptake of MIBI in thyroid nodules was compared with that in the surrounding normal thyroid tissue, and a score of between 0 and 3 was assigned to each nodule as follows: 0, cold; 1, decreased; 2, equal; 3, hot. Definitive histology revealed nodular goitre in 24 cases, adenoma in 19, thyroiditis in 1, differentiated cancer in 12, medullary cancer in 2, and anaplastic cancer in 1. None of the degenerative nodules were hot on MIBI scan, while the adenomas showed a variety of MIBI imaging patterns, most frequently the score 3 pattern. In the diagnosis of differentiated thyroid cancer the sensitivities of score 3 and score 2+3 MIBI uptake patterns were 83% (10/12) and 100%, respectively. The score 3 MIBI uptake pattern had a specificity of 100% and a positive predictive value of 100% with respect to thyroid (benign and malignant) neoplastic diseases, whereas a specificity of 72% and a positive predictive value of 43% were observed in the detection of differentiated cancer. After a cold nodule had been detected using 99mTc-pertechnetate, a second scan with high MIBI uptake increased by 7.8 times the probability that this nodule would be a differentiated cancer. In conclusion, 99mTc-MIBI scintigraphy is a useful method in the differential diagnosis of cold thyroid nodules if the primary aim is to differentiate degenerative from neoplastic diseases rather than to differentiate benign from malignant nodules. High MIBI uptake considerably increases the probability of a differentiated thyroid cancer and facilitates immediate surgical removal, while decreased uptake actually excludes it. We suggest a combination of fine-needle aspiration biopsy and MIBI scan as a routine diagnostic approach to cold thyroid nodules.

Altered signal pathway in angiotensin II-stimulated neutrophils of patients with hypercholesterolaemia

Angiotensin II (AII) in 1-10 nM concentrations has an in vivo immunostimulating effect on human neutrophils. The release of superoxide anions and leukotrienes (LTs) is significantly increased by 10 nM AII-stimulated neutrophils of patients with hypercholesterolaemia (HCH). These oxidizing agents may be involved in the damage of vessel walls, i.e., in atherosclerotic plaque formation. To clarify the receptor types and signal pathways in neutrophils of healthy controls and patients, inositol trisphosphate (IP(3)) production and Ca(2+) signalling were studied. Neutrophils were pretreated before AII stimulation with different inhibitory drugs. In control cells, the stimulation occurred predominantly through pertussis toxin-sensitive, type angiotensin 1 receptors. This induced IP(3) production and Ca(2+) signalling from intracellular pools. In neutrophils of hypercholesterolaemic patients, the enhanced release of oxidizing agents was dependent more on type angiotensin 2 than type angiotensin 1 receptors. After stimulation, there was no IP(3) production detected. The Ca(2+) signalling was lower than in control cells and was dependent on extracellular Ca(2+).

Cytochemical studies on the fibroblast-preadipocyte relationships in cultured fibroblast cell lines.

The theoretical basis of adipogenesis has always been a matter of debate. One concept suggests that all types of adipocytes are derived from undifferentiated connective tissue cells, whereas another concept suggests that adipocytes develop from specialized cells only that are able to accumulate fat. Many conflicting data have been published with respect to the transition of fibroblasts into preadipocytes. For example, this transition has been declared as impossible for dermal and perimysial fibroblasts. The present study analysed spontaneous accumulation of fat in various types of fibroblasts from different origin (retroocular, skin, NIH/3T3, and L929). It was found that intense Oil Red O-positive triglyceride-containing droplets accumulated in practically all types of fibroblasts provided that the cells were cultured on glass surface. When the cells were cultured on plastic surfaces, lipid staining was inhibited in a variable manner: inhibition was virtually complete in skin fibroblasts, whereas in other types of fibroblasts, inhibition was only partial. It is concluded that all types of fibroblasts can accumulate fat spontaneously, and thus can be considered as preadipocytes. Therefore, interpretations of data obtained with cultures of fibroblasts with respect to adipogenesis have to be reconsidered.

Specific and scavenger low-density lipoprotein receptors involved in the disturbed lipid metabolism of patients with non—insulin-dependent diabetes mellitus are independent of obesity

Comparative studies were performed on monocyte-derived macrophages (MDMs), prepared by a 72-hour incubation of blood monocytes obtained from patients with non-insulin-dependent diabetes mellitus (NIDDM) and age-matched obese and non-obese controls. The MDMs, after a 72-hour culturing, expressed both specific and scavenger low-density lipoprotein (LDL) receptors on their surfaces. To study the binding capacity of both receptor types, [125I]LDL and [125I] acetylated LDL (acLDL) were applied to cells and the labeled ligands were then monitored to estimate the rate of intracellular degradations. The LDL-induced inhibition of endogenous cholesterol synthesis and the acLDL-triggered apolipoprotein (apo) E secretion were also studied, as the biological marker of receptor activation. The results indicate that the binding capacities of both specific and scavenger LDL receptors were not reduced in MDMs of diabetic patients. However, the intracellular degradation after LDL incorporation was decreased. The LDL-induced inhibition of cholesterol synthesis and the acLDL-transmitted apo E secretion were also found to be decreased in the MDMs of patients with NIDDM as compared with the obese and non-obese control groups. The NIDDM-induced impaired signal transduction of both specific and scavenger LDL receptors suggests an unclarified functional alteration of both receptor structures.