Dementia with Lewy bodies (DLB) causes elevated outlays for the National Health Systems due to high institutionalization rate and patients’ reduced quality of life and high mortality. Furthermore, ...DLB is often misdiagnosed as Alzheimer’s disease. These data motivate harmonized multicenter longitudinal cohort studies to improve clinical management and therapy monitoring. The Italian DLB study group of the Italian Neurological Society for dementia (SINdem) developed and emailed a semi-structured questionnaire to 572 national dementia centers (from primary to tertiary) to prepare an Italian large longitudinal cohort. The questionnaire surveyed: (1) prevalence and incidence of DLB; (2) clinical assessment; (3) relevance and availability of diagnostic tools; (4) pharmacological management of cognitive, motor, and behavioural disturbances; (5) causes of hospitalization, with specific focus on delirium and its treatment. Overall, 135 centers (23.6 %) contributed to the survey. Overall, 5624 patients with DLB are currently followed by the 135 centers in a year (2042 of them are new patients). The percentage of DLB patients was lower (27 ± 8 %) than that of Alzheimer’s disease and frontotemporal dementia (56 ± 27 %) patients. The majority of the centers (91 %) considered the clinical and neuropsychological assessments as the most relevant procedure for a DLB diagnosis. Nonetheless, most of the centers has availability of magnetic resonance imaging (MRI; 95 %), electroencephalography (EEG; 93 %), and FP-CIT single photon emission-computerized tomography (SPECT; 75 %) scan for clinical applications. It will be, therefore, possible to recruit a large harmonized Italian cohort of DLB patients for future cross-sectional and longitudinal multicenter studies.
To evaluate possible cause-effect relationships between hyperostosis frontalis interna and cognitive dysfunction, we performed a neurophysiological (event-related potentials, ERPs) and ...neuropsychological study in a case of Morgagni-Stewart-Morel (MSM) syndrome associated with frontal lobe compression. Neuropsychological evaluation evidenced selective impairment of executive function. Visual and auditory oddball ERPs revealed delayed P300 latency and reduced auditory P300 amplitude with multi-peaked morphology. ERP abnormalities and cognitive dysfunction could be due to the frontal bone-cortex conflict documented by neuroradiological investigations.
We describe the genetic analysis of an Alzheimer's disease (AD) sample derived from a genetically isolated population. Genetic assessment included the analysis of genes involved in AD, such as the ...genes for amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). We also assessed genes for some proteins that constitute the γ-secretase complex: nicastrin (NCSTN), presenilin enhancer-2 (PEN2), in addition to the AD risk factor apolipoprotein E (APOE). Using polymerase chain reaction and single strand conformational polymorphism method, screens for APP, PSEN1 and PSEN2 genes revealed one mutation in PSEN1. Furthermore, we found an intronic +17G
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C polymorphism in PEN2 which, in homozygous form, was greater in early onset Alzheimer's disease (EOAD) compared to controls, and one haplotype in the NCSTN gene which was linked to EOAD and familial AD (FAD). Finally, the genotyping of APOE confirmed that the ɛ4 allele could be a risk factor for the onset of AD, in particular for FAD subjects. In conclusion, these results show the existence of Sardinian genetic peculiarities, essential in studies regarding genetically inherited and multifactorial disorders, as AD.
Cholesterol distribution in tumoral tissues and lipid composition in the plasma compartment were determined in patients affected by different histologic types of lung cancer. The results showed that ...tumoral lung tissues contained 2-fold more total cholesterol and 3.5-fold more esterified cholesterol than normal lung tissues. In the patients the alterations in intracellular cholesterol were also associated with peculiar changes in cholesterol distribution in the plasma compartment. Serum high-density lipoprotein (HDL) cholesterol levels were markedly lower in than in controls. No significant changes in other lipid parameters were observed in these patients. We suggest that the reduced levels of serum HDL cholesterol observed in patients with lung tumors may be a consequence of the disease, probably mediated by the greater utilization of cholesterol for new membrane biogenesis and by the accumulation of esterified cholesterol in tumoral tissues.
This work was designed to study the proliferative response of tumor-associated lymphocytes (TAL) from neoplastic effusions against autologous tumor cells and the immunophenotype pattern of TAL from ...neoplastic effusions and that of PBMC of the same patients. We also compared the serum levels of the cytokines interleukin (IL) 1 beta, 2 and 6, tumor necrosis factor-alpha (TNF alpha) and soluble IL-2 receptor (sIL-2R) with those present in neoplastic effusions of the same patients. Moreover, we examined the ability of TAL and peripheral blood mononuclear cells (PBMC) to produce and release the cytokines and sIL-2R and to express membrane CD25 following their stimulation with phytohemagglutinin (PHA) in vitro. Finally, we compared the cytokines/sIL-2R production and membrane CD25 expression by PHA-stimulated PBMC of the patients with neoplastic effusions with a series of 90 cancer patients without neoplastic effusions and 20 normal healthy subjects. Thirteen neoplastic pleural and eight peritoneal effusions were collected from 11 patients with primary lung cancer, 7 with primary epithelial ovarian cancer, 1 with breast cancer, 1 with pleural mesothelioma, and 1 with pancreatic cancer. The proliferative response of TAL from neoplastic effusions against autologous tumor cells was lower than the response to PHA, IL-2, and anti-CD3, but significant. The percentage distribution of CD3+ and CD8+ lymphocyte subpopulations was higher in peritoneal than in pleural effusions, while the CD16+ subset was higher in pleural than in peritoneal effusions. The percentage distribution of CD16+ was significantly lower in pleural effusions than in PBMC of patients with pleural effusions.
A hospital based case-control study was conducted to test the hypothesis of a lower lung cancer risk in G6PD-deficient subjects. Cases were 156 male patients with lung cancer, admitted to "Binaghi" ...Hospital, Local Health Unit (USL) 20, Cagliari (Italy), between January 1984 and November 1986. Controls were 235 male patients, admitted to the same hospital in the same time period, for diseases other than cancer (all types) and hemolytic anemia. No decrease of the lung cancer risk was found in G6PD-deficient subjects. This result, in line with recent reports in the literature, suggests that the genetic condition of G6PD deficiency does not provide significant protection against the development of lung cancer in humans.
We studied the apo-E polymorphism in a sample of 46 AD patients (13 males, 33 females, age at testing 45–83 years) from Sardinia, along with 582 healthy controls of the same origin. The diagnosis of ...possible or probable AD was made according to the NINCDS-ADRDA criteria: the suspicion of dementia was confirmed by history, neurological data as well as by psychometric testing. All patients had an altered Hachinski ischemic scale (HIS) score ≦ 4. Computed tomography (CT) scan, magnetic resonance imaging (MRI), and single photon emission CT (SPECT) study with 99m-Technetium-complex of demethylated propyleneamine-oxime (99m-Tc-HM-PAO) were performed in all patients. A singular feature of the neuropsychological profiles was a pattern of language deficit: our AD patients showed at the beginning of the illness a peripheral dysgraphia, a writing impairment which, in terms of the model of spelling put forward by A.V. Ellis, was considered as an inability to accede to the appropriate allograph for a grapheme. The apo-E genotypes were detected by using a polymerase chain reaction (PCR) method. A twofold increase of apo-E ε4 allele frequency in AD patients vs controls (p = 0.02) and the absence of ε2-containing genotypes were found. None of the patients was ε4 homozygous. These preliminary results suggest that in Sardinian population the ε4 allele is associated to AD whereas the ε2 allele may have a protective role in the pathogenesis of the disease.
This paper discusses inference from hypothesis-generating studies on occupational risks for lung cancer based on routine hospital records. A hospital-based case-control study on 567 male lung cancer ...patients and 906 controls provided a practical example. Among possible causes of bias, the effects of poor detail in the occupational information, of a large proportion of exclusions due to incomplete information, of cardiovascular diseases as the prevalent diagnosis among controls, of selecting cases and controls from different hospitals with likely differences in referring areas, and the problem of multiple comparisons are highlighted. Significant excess lung cancer risks were found for farmers, miners, crushers, stonemasons and cement plant workers, and stock handlers and stevedores. Positive findings with small numbers of observations are more likely to be artificially generated, but also the precision of more robust risk estimates may be affected. The limits to inference from hypothesis generating case-control studies based upon routine hospital records, such as in the example described, outweigh the advantage of the ready availability of these data-bases.
Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate, dehydrogenase the key enzymes of the hexose monophosphate shunt pathway, were measured in both surrounding and tumoral lung tissues ...from normal and G6PD-deficient subjects. A significant increase of these enzymatic activities in tumoral tissue was found not only in G6PD-normal patients, but also in G6PD-deficient patients with very low or nonmeasurable G6PD activity in both erythrocytes and normal lung tissue.
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