Hierarchical organization of the hemostatic response to penetrating injuries in the mouse macrovasculature.

Essentials Methods were developed to image the hemostatic response in mouse femoral arteries in real time. Penetrating injuries produced thrombi consisting primarily of platelets. Similar to arterioles, a core-shell architecture of platelet activation occurs in the femoral artery. Differences from arterioles included slower platelet activation and reduced thrombin dependence. SUMMARY: Background Intravital studies performed in the mouse microcirculation show that hemostatic thrombi formed after penetrating injuries develop a characteristic architecture in which a core of fully activated, densely packed platelets is overlaid with a shell of less activated platelets. Objective Large differences in hemodynamics and vessel wall biology distinguish arteries from arterioles. Here we asked whether these differences affect the hemostatic response and alter the impact of anticoagulants and antiplatelet agents. Methods Approaches previously developed for intravital imaging in the mouse microcirculation were adapted to the femoral artery, enabling real-time fluorescence imaging despite the markedly thicker vessel wall. Results Arterial thrombi initiated by penetrating injuries developed the core-and-shell architecture previously observed in the microcirculation. However, although platelet accumulation was greater in arterial thrombi, the kinetics of platelet activation were slower. Inhibiting platelet ADP P2Y12 receptors destabilized the shell and reduced thrombus size without affecting the core. Inhibiting thrombin with hirudin suppressed fibrin accumulation, but had little impact on thrombus size. Removing the platelet collagen receptor, glycoprotein VI, had no effect. Conclusions These results (i) demonstrate the feasibility of performing high-speed fluorescence imaging in larger vessels and (ii) highlight differences as well as similarities in the hemostatic response in the macro- and microcirculation. Similarities include the overall core-and-shell architecture. Differences include the slower kinetics of platelet activation and a smaller contribution from thrombin, which may be due in part to the greater thickness of the arterial wall and the correspondingly greater separation of tissue factor from the vessel lumen.

Obesity treatment in elderly outpatients: predictors of efficacy and drop-out.

OBJECTIVE: Obesity is increasing in the elderly and it is associated with an increased risk of medical complications, decline in physical function and disability. Very few studies specifically evaluated the outcome of obesity treatment in the aging patients. Aim of this work is therefore the evaluation of the efficacy of medical therapy in a group of obese patients >or=65 years old. METHODS: The study has been performed on the clinical records of obese outpatients treated at the medical branch of the Unit for Medical and Surgical Therapy of Obesity at the University of Padova. Patients were recruited from January 1st, 2001 to June 30th, 2006 in order to have patients with at least one year of potential follow-up. In particular two groups were enrolled: 100 patients >or=65 years old and 200 patients <65 years old. The baseline characteristics, the prescriptions and the treatment outcome were compared. RESULTS: Mean age of the elderly patients was 69.1+/-3.7 years (range 65-80 years). We did not find any significant difference between elderly and adult patients in the sex distribution (female patients 76% in the elderly group and 72% in the adult group; p=0.276) and in the severity of overweight (body mass index: 37.8+/-6.0 kg/m2 in the elderly; 37.2+/-6.3 kg/m2 in adults; p=0.425). The elderly group was characterized by a higher incidence of comorbidities and a lower incidence of eating behavior disorders at baseline. No significant differences in the dietary prescription were found, whereas physical activity was prescribed in 27/100 elderly patients (27%) and in 97/200 (48%) adults patients (p<0.000). Weight loss was evaluated by analyzing the percentage of patients reaching at least a 10% weight loss from baseline after 12 months of treatment. In elderly patients still in active treatment after 12 months, only 5/28 (18%) patients reached the specified goal, whereas in adult patients still in treatment, 18/47 (38%) patients reached the goal (p<0.05). Lower age at baseline, female sex, and lower body mass index were found to be the only significant predictors of 10% weight loss in logistic regression. In our experience, drop-out rate after 12 months was similar in adults (77%) and in older patients (72%). In a multivariate Cox regression model, the risk of drop-out was reduced by married or widowed status, the prescription of physical activity at baseline, and the presence of type 2 diabetes. The risk of drop-out was increased by the presence of osteoarthritis. Even after adjustments for these confounding variables, age did not play any significant role as drop-out predictor. CONCLUSION: Advanced age seems to be a predictor of poor response to treatment in obese outpatients treated by conventional medical therapy. Drop-out rate was not significantly influenced by age.

A retrospective pilot study on the development of cognitive, behavioral and functional disorders in a sample of patients with early dementia of Alzheimer type.

This pilot study retrospectively analyzes the evolution of cognitive-behavioral symptoms and functional autonomy in a sample of patients with early diagnosis of probable Alzheimer's disease (AD). One hundred patients with early mild cognitive impairment (MCI) were considered and submitted to a multidimensional evaluation: the 53% presented probable AD. These 53 subjects were evaluated for cognitive performance by using the mini mental examination (MMSE), behavioral functions by the neuropsychiatric inventory (NPI) and functional dependence by the activities of daily living (ADL) and the instrumental ADL (IADL) scales at basal time and after 6-12 months. Results were analyzed according to the duration of therapy with acetyl-cholinesterase inhibitors (ACHEI) and to the timing of the beginning with respect to the diagnosis. AD patients treated with ACHEI at the moment of the diagnosis, showed a statistically significant improvement in MMSE (2.7+/-1.5) after 6 months (p=0.012) which was maintained even after 12 months. Subjects beginning ACHEI at the visit of 6 months showed a statistically worsened MMSE, even after 6 months of therapy (-2.8+/-1.7, p=0.026). We conclude that the timing of administration of ACHEI therapy in mild AD is essential to obtain beneficial effects on cognitive decline.

Serial position effect in a free recall task: differences between probable dementia of Alzheimer type (PDAT), vascular (VaD) and mixed etiology dementia (MED).

Here we report an investigation on the serial position effect (SPE) in elderly patients with early dementia due to different etiologies. The Rey's 15 words test has been used to evaluate whether different types of dementia show different patterns of immediate and delayed recall and of learning process. Ninety-four patients were recruited from the Geriatric Clinic of Padua. We evaluated the primacy effect (PE), the recency effect (RE) and the learning process within the sample. Our results indicate that different etiologies have different patterns of anterograde memory impairment.

Cryptic hepatitis B virus replication during prednisone therapy in type B chronic active hepatitis.

Hepatitis B virus (HBV) replicating in patients with serum hepatitis B surface antigen and antibody to hepatitis B e antigen (cryptic HBV replication) can be detected by a spot hybridization technique for serum HBV-DNA and by immunoperoxidase staining of hepatitis B core antigen in the liver. These methods allowed us to study the effects of chronic (13 to 82, mean 30 months) administration of low doses (10 or 15 mg/day) of prednisone to 17 patients with chronic active hepatitis and cryptic HBV replication. Liver biopsies performed before treatment demonstrated that 1 to 50% (mean 12%) of the liver cells were infected. After therapy, infected cells had disappeared in 5 (29%), were considerably reduced in 9 (53%) and remained unchanged in 3 (18%) patients. The mean percentage of infected cells in the liver biopsies performed at the end of the follow-up was 3.2 +/- 5.5% (p less than 0.005). Serum HBV-DNA was present in 12 of 13 and in 5 of 12 patients investigated before treatment and at the end of the study, respectively. Five patients harboring HBV in the liver developed cirrhosis during treatment. Our data indicate that, despite steroid therapy, HBV replication either ceased or was decreased in two thirds of the patients, while in no case it flared-up. The rise of cirrhosis was not prevented by this type of therapy.