The aim of this review is to report the current evidence on immunogenicity of monoclonal antibodies (moAbs) used in cancer compared with autoimmune diseases, focusing on local microenvironment. English abstracts were identified in Medline and www.clinicaltrials.gov . A total of 82 papers were selected. The percentage of immunogenicity of moAbs used for cancer therapy, evaluated as the serum concentration of antidrug antibodies, is significantly lower than that of moAbs used for the treatment of autoimmune diseases. This condition may rely on a different immunologic background characterized by a hyperactivation of immune cells in autoimmune diseases. The formation of complexes between antidrug antibodies and non-neutralizing moAbs bound to neoplastic antigens may allow more efficient elimination of cancer cells, but additional studies are needed.
In a prospective double-blind study, single dose lumbar extradural blockade was instituted in 80 healthy male patients undergoing lower abdominal surgery. Patients were assigned randomly to one of four groups. Each group received treatment with 0.5% bupivacaine 20 ml containing adrenaline 1:200 000. To this solution was added fentanyl 0, 50, 100 or 200 micrograms. The time to regression of analgesic blockade was significantly prolonged (P less than 0.05) only with mixtures containing fentanyl 200 micrograms; no effect was demonstrated with lower doses of the opioid. However, the degree of motor blockade was less intense and incomplete S1-blockade (root-jumping) was more frequent with mixtures containing increasing doses of fentanyl. Patients treated with bupivacaine-fentanyl mixtures shivered less than the control group and showed fewer instances of acute hypotension. The side-effects observed were minor.
The "applause sign" is a motor perseveration described in focal and neurodegenerative disorders and characterized by fronto-subcortical dysfunction. Most previous formal investigations focused on Parkinson's disease or progressive supranuclear palsy. We assessed the prevalence of the applause sign in patients affected by Alzheimer's disease (AD), Lewy body dementia (LBD), corticobasal syndrome (CBS), and posterior cortical atrophy (PCA), with the aim to verify its contribution to the differential diagnosis. We enrolled 20 patients with AD, 20 with LBD, 16 with CBS, and ten with PCA, and 30 healthy controls. The three clap test (TCT) was used to elicit the applause sign, and was scored by raters blinded to the diagnosis. Correlation with motor (extrapyramidal) and cognitive measures was also performed. A maximum 40 % prevalence of a positive applause sign was found in the two parkinsonian syndromes, which could be discriminated from the two cortical groups with a positive predictive value of 82 % and a negative predictive value of 55 %. According to our findings, a diagnosis of LBD or CBS, rather than of AD or PCA, is highly probable in the presence of an abnormal TCP, but cannot be ruled out based on a negative result. No relevant correlates emerged that could clarify the origin and nature of the applause sign.
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