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Down's syndrome (DS) subjects are at high risk of developing Alzheimer's disease (AD). Patients with AD often show altered levels of some immune molecules in their peripheral blood which correlate with cognitive impairment. However, whether the altered peripheral immune phenotype is a late and secondary phenomenon associated with dementia or an early impairment linked to mechanisms controlling neurodegeneration of the central nervous system (CNS) is still an unanswered question. Here we studied immune molecules in the blood of non demented children with DS to investigate whether altered peripheral immune phenotype could be present in these subjects without dementia, many years before the presentation of clinical signs of cognitive deterioration. Plasma levels of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) were significantly higher in DS than in control children. Plasma levels of soluble intercellular adhesion molecule-3 (sICAM-3), soluble vascular cell adhesion molecule-1 (sVCAM-1) and C reactive protein (CRP) were also increased in DS. The increase of IL-6 and CRP from DS children was similar to that found in elderly patients with clinical AD. Peripheral altered immune phenotype in healthy young subjects with DS might be an early sign of CNS alterations leading many years later to cognitive deterioration and dementia.

In-vitro and animal studies have shown that viral agents can be removed from or inactivated in clotting factor concentrates by physical or chemical treatment. However, clinical data have as yet not substantiated the results of these studies. 13 haemophilia A patients who had not been treated previously with blood or blood products were given a dry-heated factor VIII concentrate and were tested serologically over the next 12 months. Hepatitis developed in 11 patients (84%) and was invariably of type non-A, non-B. Morbidity was not related to the lot of the therapeutic material or to the number of infusions. The incubation period was either 5 or 8-11 weeks, and only 1 patient had symptoms. Aminotransferase elevation showed both monophasic and biphasic patterns. During the follow-up period signs of the disease disappeared in 10 patients (90%). These findings contrast with the absence of non-A, non-B hepatitis in chimpanzees given the same heated concentrate. Thus, clinical studies in first- exposure hæmophiliacs are essential for the true evaluation of the safety of new “treated” concentrates.

We recently reported two cases of QT interval prolongation and cardiac arrest in newborns receiving antibiotic therapy with spiramycin, a macrolide agent extensively used for toxoplasmosis prophylaxis. In this study we assessed the effects of this drug on ventricular repolarization and on the potential risk of lethal arrhythmias in eight newborn infants in whom toxoplasmosis prophylaxis after birth was necessary. Electrocardiograms (ECGs) and echocardiograms were recorded during spiramycin therapy (350,000 IU/kg/day) and after its withdrawal. In a control group of eight healthy newborns matched for age and sex, no differences were found between two ECGs analogously recorded. The QT interval corrected for heart rate (QTc) was longer during spiramycin therapy than after drug withdrawal (448 +/- 32 msec vs 412 +/- 10 msec, +9%, p = 0.021). QTc dispersion, expressed as the difference between the longest and the shortest value in 12 different leads (QTc "m"a"x" "-" "m"i"n ), was also higher during spiramycin therapy (60 +/- 32 msec vs 34 +/- 8 msec, +76%, p = 0.021), mainly because of a major lengthening of the longest QTc (QTc "m"a"x ). QTc and QTc dispersion were markedly increased in the two newborns who experienced cardiac arrest after beginning treatment compared with the six neonates who had no drug-induced symptoms. During therapy seven of eight newborns had a rare abnormality in the thickening of the left ventricular posterior wall similar to that observed in patients with congenital long QT syndrome. This abnormality disappeared after drug withdrawal. Thus antibiotic therapy with spiramycin in the neonatal period may induce QT interval prolongation and increase QT dispersion. When this effect on ventricular repolarization is more marked, it may favor the occurrence of torsades des pointes and lead to cardiac arrest. (Am Heart J 1997;133:108-11.)