The role of sonoelastography in the differential diagnosis of neck nodules.

Sonoelastography is an imaging technique that provides information on tissue elasticity. Its use as a diagnostic procedure is based on the premise that pathological processes like cancer alter the physical characteristics of the involved tissue. Ultrasonographic studies of the neck can reveal the nonpalpable thyroid nodules, but the nature of these lesions generally has to be established on the basis of FNAB findings. In our hands, sonoelastography displayed a diagnostic accuracy of 86.2% in identifying thyroid nodule malignancy, with positive and negative predictive values (PPV and NPV) of 64% and 94.5%, respectively. In the study of cervical lymph nodes, the results were less impressive (sensitivity 75%, specificity 80%, accuracy 77%, PPV 80%, NPV 70%), but the information obtained with this technique can in our opinion be a useful adjunct to sonographic findings. Indeed, in 5 lymph nodes with sonographic features consistent with malignancy, sonoelastography revealed diffuse elasticity that was indicative of benign disease, which was confirmed by pathological studies. Other nodular lesions of the neck can also be evaluated with sonoelastography, including enlarged parotid glands, but the data in the literature are too limited to allow hypotheses on the role of this imaging modality in this field. Sonoelastography is rapid and simple to perform, and it appears to be a potentially useful tool for the differential diagnosis of neck nodules. This is particularly true of thyroid nodules. Our experience with these lesions indicates that diffuse elasticity is strongly correlated with benign disease. If this finding is confirmed in larger studies, sonoelastography might be used to identify thyroid nodules that do not require immediate biopsy.

A Thr359Met mutation in factor VII of a patient with a hereditary deficiency causes defective secretion of the molecule.

We elucidated the genetic basis responsible for factor VII deficiency in an Italian woman with a severe bleeding diathesis. In the allele inherited from the patient's father, we identified a G to A mutation at nucleotide 6070 at the 5' splice site of intron 4 and a G to A substitution at nucleotide 10976 resulting in the Arg353Gln polymorphism. The maternal allele demonstrated a C to T substitution at nucleotide 10994 resulting in Thr359Met. The mutation at nucleotide 6070 alters an invariant GT dinucleotide and disrupts normal mRNA processing. To investigate the mechanism by which Thr359Met reduces factor VIl levels, we expressed wild type factor VII cDNA (FVIIwt) and a mutant factor VII cDNA containing the base substitution resulting in Met359 (FVII359M) in Chinese hamster ovary cells (CHO). In cells transfected with the mutant factor VII cDNA, FVII359M accumulated intracellularly, and no factor VII was detected in the media after 3 hours of chase. The carbohydrate side chains associated with FVII359M were sensitive to Endo H digestion, which indicates that the protein is retained in the endoplasmic reticulum. Analysis of cell lysates also showed that FVII359M was associated with the 78 kD protein corresponding to GRP78/BiP. We conclude that a Thr359Met mutation in factor VII results in a severe secretion defect that probably results from abnormal folding of the molecule.

Multicentric evaluation of a new assay for prothrombin fragment F1+2 determination.

A multicenter study of a recently developed ELISA for the determination of prothrombin fragment F1+2 was performed in order to evaluate analytical and clinical aspects. Mean intra-assay and inter-assay reproducibility were found to be 11.0 and 12.6%, respectively. The measuring range covered by the calibration curve reaches from 0.04 to 10.0 nM/l F1+2. Testing 133 healthy subjects a reference range of 0.37 to 1.11 nM/l F1+2 (2.5-97.5 percentile) with a median of 0.66 nM/l F1+2 was calculated. Minor difficulties with blood sampling (venous occlusion for 2 min) did not affect F1+2 plasma concentrations. Significantly increased F1+2 levels were measured in patients with leukemia (p < 0.0001), severe liver disease (p < 0.005) and after myocardial infarction (p < 0.01). Elevated F1+2 concentration before the beginning of heparin therapy (1.25 nM/l) decreased to 0.77 nM/l (p < 0.0001) after 1 day of therapy. For patients in the stable phase of oral anticoagulant therapy decreasing F1+2 concentrations were measured with increasing INR. F1+2 levels were already significantly reduced in patients with INR < 2.0 (0.56 nM/l; p = 0.0005). Thus F1+2 determination may be helpful in identifying activation processes as well as in monitoring anticoagulant therapy.

[Hormonal investigations in a patient with mucopolisaccharidosis (author's transl)]. / Indagini ormonali in un soggetto affetto da mucopolisaccaridosi

In one patient with mucopolisaccharidosis endocrine investigation were performed. The results indicate an impaired regulation of hypothalamus-hypophysis-adrenocortical system. The hypothalamus GH sstem appears to be involved to a lesser extent. A dysfunction of the central nervous system is suggested.