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Background: Sporadic Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disease caused by prions that is randomly distributed in all countries, with an overall yearly mortality rate of about 1-2 cases per million people. On a few occasions, however, sporadic CJD occurred with higher than expected rates, but further investigations failed to recognize any convincing causal link. In Italy, cluster analyses of sporadic CJD cases have not been performed previously., Objective: To investigate the geographical distribution of sporadic CJD using municipality geographical data of Apulia with the aim of detecting spatial clusters of disease., Patients and Methods: Patients included in this study were diagnosed as probable or definite sporadic CJD and were residents of the Apulia Region (Italy). Bayesian hierarchical models with spatially structured and unstructured random components were used to describe the spatial pattern of the disease and to assess the extent of heterogeneity among municipalities. The Kulldorff-Nagarwalla scan test and the flexible spatial scan statistic were used for detecting spatial clusters., Results: Smoothed Bayesian relative risks above the null value were observed in a few adjacent municipalities in the north and middle areas of Apulia. However, both the circular scanning method and the flexible spatial scan statistic identified only a single cluster in the central part of the region., Conclusion: Geographical analyses and tests for spatial randomness identified a restricted area with an unusually high number of sporadic CJD cases in the Apulia region of Italy. Environmental and genetic risk factors other than mutations in the prion protein gene however, need to be investigated., (© 2019 S. Karger AG, Basel.)

A water-oil microemulsion and an aqueous solution, both carrying pertechnetate, were injected subcutaneously in rabbits; release was observed by imaging the administration sites with a gamma-camera. Disappearance from the injection site of pertechnetate in aqueous solution was about ten times faster than that of pertechnetate in a microemulsion.

Both CBF and CBV were evaluated by gamma-camera SPECT in 14 patients with classic migraine, all studied while symptom-free. Nuclear data were correlated with CT and MRI. A decreased regional CBF was observed in 13 of the 14 patients. The decreased perfusion was localized in the frontal lobe in 6 patients, the temporal lobe in one, the parietal lobe in 11 and the occipital lobe in 5 patients. The parieto-occipital cortex was involved more often than the frontal cortex; the association of hypoperfusion with parieto-occipital cortex was quite high. The right parieto-occipital regions were affected more often than the left ones. Regional CBV was increased in 8 patients. There was good topographical concordance between decreased CBF and increased CBV, but the increase of CBV was in general more evident at the periphery of the hypoperfusion. It is of interest that the only patient with a normal CBF study had a pathological CBV study. Apparently, CBF derangements are very common in symptom-free patients with classic migraine, a CBF decrease being often accompanied by a CBV increase. In these patients both CT and MRI have a lower diagnostic yield than SPECT.

The specific insulin binding activity of human promyelocitic HL 60 cell line during the myeloid and macrophagic differentiation induced by chemical compounds was investigated. Dimethyl sulfoxide (DMSO) and retinoic acid myeloid induced differentiation in HHL 60 cells was accompanied by a marked decrease of insulin receptors. In K 562 cell line, where DMS O has no effect on differentiation, the number of insulin receptors was only slightly affected. 12-0-tetradodecanoil phorbol 13-acetate (TPA) induced macrophagic differentiation of HL 60 cell line was also accompanied by a decrease of insulin binding activity. Our results support the hypothesis that during the process of terminal differentiation a decrease of insulin receptors occurs.

The immunogenicity of conventional therapeutical insulin is discussed according to the concepts of Schlichtkrull: the formation of insulin antibodies is not attributable to the pure Sanger's insulin molecule, but to related protein impurities, present in all crystallized pig and ox insulin preparations. The terms of monocomponent insulin, highly purified insulin, and single peak insulin in defined and personal clinical results obtained with Novo Monocomponent Lente Insulin over a period of 3 years are presented. The Hein Christiansen's radioimmunoelectrophoretic method fo estimation of 125I-insulin IgG binding was used to determine insulin antibody levels. It was found that: 1) Newly detected insulin-dependent diabetics, never previously treated with insulin, do not produce insulin antibodies at a significant level; 2) Long-term insulin treated diabetics, transferred to monocomponent treatment, tend to reduce their antibody levels, if initially high, altough with transient recurrent peaks; 3) Stimulation of the immunocompetent system by intercurrent infection does not generally modify the immunological situation. Apart from immunological changes, satisfactory clinical results were observed in cases of high insulin requirement, insulin allergy, insulin lipoatrophy. Present practical indications for monocomponent insulin therapy (Actrapid-Lenta) are proposed.

The insulin binding characteristics of human promyelocitic HL60 cell line was studied by the use pf I(125) insulin. The binding activity was found to increase linearily both with the number of cells and with the incubation time. The competition curve with increasing concentration of unlabeled insulin demonstrated of specific receptors. The number of receptors was estimated to be 6.36 . 10(6) per cell.

On the basis of personal experience concerning 2020 consecutive determinations, the radioimmunoelectrophoretic method of Christiansen for 125I-Insulin-Binding to IgG (= IB, significant limits = mU/ml) has been proved as a reliable tool for the evaluation of insulin antibody titer in clinical diabetology. After a critical review of the recent literature about insulin antibodies both without and after exogenous immunization, the following results are presented and discussed. 1) - In 163 diabetic subjects, never previously treated with insulin, the mean value of IB was X = 0,008 mUml (sigma = 0,023 . Sx = 0,002). 2) - In 221 longterm insulin-treated diabetics the mean value of IB was X = 1,50 mU/ml (sigma = 2,15 . Sx = 0,145). 3) -In 46 insulin-dependent diabetics, serial determinations of IB allowed to follow the insulin antibody production during a 5 years treatment with monocomponent insulin )Lente MC). No or slight antibody formation was observed in newly diagnosed patients, never previously treated with insulin. High antibody starting levels showed tendency to a gradual reduction, after switching from conventional insulin treatment to the monocomponent one. These modifications in the IB values have been studied in correlation with the clinical course of conditions possibly referred to an immunologic pathogenesis, such as: brittle diabetes, high insulin requirement, insulin allergy, insulin lipoatrophy, diabetic microangiopathy. No significant variations in IB values were observed after viral infections.