In vivo functional evaluation of central cholinergic circuits in vascular dementia

OBJECTIVE: Central cholinergic circuits of human brain can be tested non-invasively by coupling peripheral nerve stimulation with transcranial magnetic stimulation of motor cortex. This test, named short latency afferent inhibition (SAI) has been shown in healthy subjects to be sensitive to the blockage of muscarinic acetylcholine receptors and it is impaired in Alzheimer disease (AD) patients, a cholinergic form of dementia, while it is normal in non-cholinergic forms of dementia such as fronto-temporal dementia. The objective of present study was to evaluate central cholinergic circuits in patients with Vascular Dementia (VaD). METHODS: We evaluated SAI in a group of patients with VaD and compared the data with those from a group of AD patients and a control group of age-matched healthy individuals. RESULTS: Mean SAI was normal in VaD patients while it was significantly reduced in AD patients. The analysis of individual data showed abnormal SAI in 75% of AD and in only 25% of VaD. CONCLUSIONS: SAI is normal in most of VaD patients in contrast with AD patients. This test might be used for the functional evaluation of central cholinergic circuits in VaD patients. SIGNIFICANCE: SAI testing may represent a useful additional tool for the evaluation of patients with VaD however, further studies are required in order to evaluate whether this method can be used for the differential diagnosis between pure VaD and different forms of dementia.     

Carboplatin (Paraplatin; JM8) and etoposide (VP-16) as first-line combination therapy for small-cell lung cancer

Fifty-two previously untreated patients with small-cell lung carcinoma (SCLC) were treated with a combination of carboplatin 300 mg/m2 intravenously (IV) on day 1 and etoposide 100 mg/m2 IV on days 1 through 3 every 28 days for four courses. Patients with limited disease (LD) subsequently received thoracic radiotherapy; no prophylactic cranial radiotherapy was used. Forty-four patients (85%) achieved an objective response, including 82% (29% complete remissions) of LD patients and 88% (13% complete remissions) of extensive-disease (ED) patients. Median response duration for LD patients was 7 months and 5.5 months for ED patients. Median survival for both LD and ED patients was 9.5 months. Myelosuppression was the main toxicity, with World Health Organization (WHO) grade 3/4 leucopenia occurring in 44% of patients. There was one (2%) treatment-related neutropenic death. Treatment was otherwise well tolerated, and in particular no renal toxicity, neurotoxicity, or ototoxicity was seen. This new combination is highly active in terms of response rate, but response duration and survival is disappointing, and might be improved by prolonged treatment or by the use of additional drugs in combination.     

Enzyme replacement therapy in adult‐onset glycogenosis II: Is quantitative muscle MRI helpful?

Although it has been shown that muscle magnetic resonance imaging (MRI) improves the phenotypic characterization of patients with neuromuscular disorders and allows accurate quantification of muscle and adipose tissue distribution, to date quantitative MRI has not been used to assess the therapeutic response in clinical trials of neuromuscular diseases. We discuss quantitative MRI findings after a 6‐month course of enzyme replacement therapy administered to nine patients with adult‐onset glycogenosis II. Muscle Nerve 40: 122–125, 2009     

Tissue factor in human coronary atherosclerotic plaques

The rupture or fissuring of a coronary atherosclerotic plaque and subsequent thrombosis is considered the key event in the pathogenesis of unstable angina and myocardial infarction. Although plaque disruption frequently occurs during the evolution of atherosclerosis, only a minority of ruptured plaques develop thrombosis. The content and procoagulant activity of tissue factor in human coronary atherosclerotic plaques varies widely, and different studies confirm that it is higher in the plaques extracted from patients with unstable angina, myocardial infarction or histologic/angiographic evidence of coronary thrombosis than in those taken from patients with stable angina or uncomplicated coronary lesions. Variations in tissue factor content and activity may be responsible for the different thrombotic responses to human coronary atherosclerotic plaque rupture.     

Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation.

Stunted growth is a major complication of chronic inflammation and recurrent infections in children. Systemic juvenile rheumatoid arthritis is a chronic inflammatory disorder characterized by markedly elevated circulating levels of IL-6 and stunted growth. In this study we found that NSE/hIL-6 transgenic mouse lines expressing high levels of circulating IL-6 since early after birth presented a reduced growth rate that led to mice 50-70% the size of nontransgenic littermates. Administration of a monoclonal antibody to the murine IL-6 receptor partially reverted the growth defect. In NSE/hIL-6 transgenic mice, circulating IGF-I levels were significantly lower than those of nontransgenic littermates; on the contrary, the distribution of growth hormone pituitary cells, as well as circulating growth hormone levels, were normal. Treatment of nontransgenic mice of the same strain with IL-6 resulted in a significant decrease in IGF-I levels. Moreover, in patients with systemic juvenile rheumatoid arthritis, circulating IL-6 levels were negatively correlated with IGF-I levels. Our findings suggest that IL-6-mediated decrease in IGF-I production represents a major mechanism by which chronic inflammation affects growth.