Oligomeric and fibrillar amyloid beta 42 induce platelet aggregation partially through GPVI.

The effects of the Alzheimer's disease (AD)-associated Amyloid-ß (Aß) peptides on platelet aggregation have been previously assessed, but most of these studies focused on Aß40 species. It also remains to be determined which distinct forms of Aß peptides exert differential effects on platelets. In AD, oligomeric Aß42 species is widely thought to be a major contributor to the disease pathogenesis. We, therefore, examine the ability of oligomeric and fibrillary Aß42 to affect platelet aggregation. We show that both forms of Aß42 induced significant platelet aggregation and that it is a novel ligand for the platelet receptor GPVI. Furthermore, a novel binding peptide that reduces the formation of soluble Aß42 oligomers was effective at preventing Aß42-dependent platelet aggregation. These results support a role for Aß42 oligomers in platelet hyperactivity.

The use of silver amalgam for treatment of shell ulcerations in turtles: 60 cases.

Shell ulcers were diagnosed based on clinical appearance in 60 turtles. Under general anaesthesia, surgical curettage was performed using a burr mounted on a micro-grinder. A calcium hydroxide paste was applied to the debrided lesions before the application of restorative material. Lesions were completely filled with rapidly hardening silver amalgam. Treated terrapins were hospitalised in dry containers and later were housed in tanks with controlled temperature 24 hours. Fillings were found spontaneously expulsed at various periods after placement. No signs of mercury poisoning or tissue reaction to the prosthesis were apparent.

Childhood osteosarcoma: Incidence and survival in Argentina. Report from the National Pediatric Cancer Registry, ROHA Network 2000-2013.

BACKGROUND: Differences in incidence and survival in osteosarcoma reports are considerable worldwide. PURPOSE: This study describes the incidence and survival of patients with osteosarcoma in Argentina with data from the National Pediatric Cancer Registry (ROHA), and the impact of age, gender, stage, regional, and socioeconomic indicators on outcome. METHODS: Pediatric patients with osteosarcoma reported to ROHA from 2000 through 2013 were analyzed, the annual age-standardized incidence rate (ASR) was calculated using the National Vital Statistics, and survival was estimated. The extended human development index (EHDI) for each reporting region was used as an indicator of socioeconomic status. RESULTS: There were 515 cases of osteosarcoma identified, yielding an ASR of 3.2/1,000,000 children (0-14 years old). The ASR did not vary significantly by year of diagnosis but ranged from 4.0/1,000,000 in the Cuyo/Western Central region to 2.7/1,000,000 in the northeast region (P < 0.000). The estimated 5-year survival rate was 45% (95% confidence interval [CI] 44-51%), with no difference by sex, diagnosis year, region, or EHDI score (P > 0.1 in all cases). Survival rate for localized disease was 52% (95% CI 45-57%) and for metastatic 22% (95% CI 15-30%). CONCLUSIONS: In Argentina, ASR of osteosarcoma is similar to that in high-income countries, but survival is lower in all regions. Future work will focus on identification and reduction of causes of preventable treatment failure.

Risk assessment in ginecology and obstetrics in Sicily: an approach based on Wolff's Criteria.

OBJECTIVES: To apply Wolff's Criteria to hospital discharge records (HDR) in order to detect adverse events worthy of further study. METHODS: Gynecology and Obstetrics Units of three Sicilian hospitals were considered and HDR regarding ordinary and day hospital admissions in 2008 were collected. A matched case-control study was designed, by random selection of 10 controls at maximum for each case. Matching was performed on the variables age and speciality of admission (gynecology or obstetrics). RESULTS: Out of a total of 7011 HDR examined, 114 cases were identified with Wolff's Criteria. Multivariate analysis confirmed a statistically significant association with the origin of admission, diagnosis at the acceptance and length of stay: there was a decreased risk of Wolff's event in patients having urgent admission compared to elective (OR = 0.47, 95% CI = [0.28-0.78]), an increased risk in patients reporting tumor (OR = 5:41, 95 % CI [1.89-15.47]) and other causes (OR = 2.16, 95% CI [1.10-4.24]) compared to delivery diagnosis at acceptance and in patients whose length of stay was more than 6 days (OR = 23.17, 95% CI = [12.56-42.7]) compared to less or equal than 3 days CONCLUSION: Wolff's Criteria can be applied for the analysis of clinical risk in hospitals with different structural characteristics, on condition that the HDR database is complete and good quality.

Olfactory discrimination predicts cognitive decline among community-dwelling older adults.

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

[An analysis of appeals against the ruling of the occupational physician's lodged to the Department of Prevention and Safety in the Working Environment--Health Prevention and Occupational Epidemiology Operative Unit within the A.S.P. Palermo (Palermo Health Authority), years 2008-2010]. / Analisi dei ricorsi "avverso giudizio del Medico Competente (M.C.)" inoltrati all'U.O.S. "Prevenzione Sanitaria e Epidemiologia occupazionale" del Servizio di Prevenzione e Sicurezza negli Ambienti di Lavoro" dell'ASP di Palermo nel periodo 2008-2010.

The purpose of this study is to analyze the appeals against a "suitability judgment for work" lodged to the U.O.S. "Health Prevention and Occupational Epidemiology Operative Unit" of Department of Prevention and Safety in the Working Environment within the ASP Palermo (U.O.S.), from 2008 to 2010. Studying the appeals gives an indirect view on the occupational physician activity and allows to monitor their actions, analysis aims at highlighting those issues around which any planning and implementation of coordination activities should be focused.

Intravenous immunoglobulin therapy for children with Stevens-Johnson syndrome.

OBJECTIVE: To review the experience with intravenous immunoglobulin (IVIG) therapy in patients with Stevens-Johnson syndrome (SJS) in our institution. METHODS: All charts of patients with SJS admitted to Children's Hospital between November 1988 and June 1998 were reviewed. RESULTS: Twelve patients with SJS were detected. There were 8 males and 4 females, with a mean age 6 years (range 10 mo to 17 yrs). All patients presented with high fever and cutaneous and mucous membrane changes, and the diagnosis SJS was confirmed by a dermatologist. Of the 12 patients with SJS, 7 were treated with IVIG, 2 with corticosteroids, and 3 with supportive care. IVIG was administered in a single infusion at 1.5-2 g/kg, and was given on an average of hospital day 3 (range 1-8 days). The average duration of fever was 8 days (range 3-14) in the IVIG treated patients compared to 14 days (range 6-20) in the non-IVIG treated group (p = 0.06). The mean hospital stay was 12 days (range 4-22) for the patients treated with IVIG and 15 days (range 6-25) for the non-IVIG treated group (p = 0.5). No toxicity was observed with IVIG therapy. CONCLUSION: Duration of fever was shortened in patients treated with IVIG, although statistical significance was marginal. The hospital stay was slightly shortened in patients treated with IVIG; however, statistical significance was not reached. Prospective and controlled, multicenter studies are needed to further investigate these preliminary findings.

The impact of coexistent diabetes on the prevalence of coronary heart disease.

The increased risk of developing cardiovascular disease in diabetic population has been well documented, but the prevalent mechanism of this susceptibility is still only partly explained. We compared the impact of diabetes on ischemic heart disease in patients hospitalized in a public general hospital over a 10-year period. The prevalence of coronary heart disease (CHD) was consistently higher among diabetic population [namely, among non-insulin-dependent diabetes mellitus (NIDDM) patients] when compared with the nondiabetic population. The prevalence was similar in both genders, increasing with age, and was independent from body-mass index, history of smoking, metabolic control, or lipid pattern. Heart rate and blood pressure levels were significantly higher in NIDDM patients with CHD; similarly, there was a significant association between ischemic heart disease and atherosclerotic peripheral artery disease prevalence, and this trend was observed even in subjects with impaired glucose tolerance. These observations support the evidence that diabetes exerts a deleterious effect on general risk factors of atherosclerosis and increases susceptibility to cardiovascular disease by itself as an "independent" risk factor; on the other hand, the epidemiological evidence of an excessive occurrence of type II diabetes in individuals with pre-existing vascular disease suggests a genetically determined link between metabolic disturbances and cardiovascular disease.

[Cardiovascular "risk" and diabetes mellitus. Results of a retrospective study]. / "Rischio" cardiovascolare e diabete mellito. Risultati di uno studio retrospettivo.

BACKGROUND: To examine the relationship of non-insulin dependent diabetes mellitus (NIDDM) with the prevalence of coronary heart disease (CHD) in a hospitalized population. METHODS AND RESULTS: Diabetes was associated with a markedly increased risk of developing CHD, whose prevalence was of 48.3% in NIDDM subjects (528 males and 661 females). Between the two groups (with and without CHD) of diabetic patients, the mean age was higher in the CHD-group, but no differences were noted with regard to gender distribution, BMI, history of cigarette smoking, alcohol consumption, glycemic control, hypoglycemic treatment, lipid pattern (although a slight increase in mean level of serum total triglycerides was observed in NIDDM subjects with CHD). On the contrary, CHD was significantly associated with a higher prevalence of periferal vascular disease (49.3% vs 32.5%) and with hypertension and renal dysfunction. CONCLUSIONS: These observations support the evidence that diabetes exerts a deleterious effect on general risk factors of atherosclerosis and increases the susceptibility to cardiovascular disease, although the prevalent mechanism of this susceptibility is only partly explained. Because the adverse "independent" effect of diabetes on the risk of cardiovascular disease is amplified in the presence of other cardiovascular risk factors, these data underscore the importance of prevention of diabetes and, once diabetes is clinically established, the need for standard risk factors management (hypertension, obesity, elevated lipid levels) as well as the development of new therapeutic strategies, in order to reduce the progress of macrovascular disease and the hemostatic derangements which may predispose to thrombosis and endothelial cell injury.

Circulating endothelin-1 levels in type 2 diabetic patients with ischaemic heart disease.

To investigate whether circulating endothelin-1 (Et-1) may be related to the increased incidence and severity of ischaemic heart disease in type 2 diabetes mellitus, we compared the concentrations in type 2 diabetic patients and in non-diabetic patients with coronary artery disease (CAD) angiographically documented. Plasma levels of Et-1 were determined in 34 type 2 diabetic patients with CAD (16 with stable angina, 6 with unstable angina, 12 with previous myocardial infarction) and in 19 nondiabetic patients with CAD (4 with stable angina, 5 with unstable angina, 10 with previous myocardial infarction). Fifteen diabetic patients without CAD and 9 healthy volunteers served as control subjects. In the type 2 diabetic patients, the mean Et-1 levels were 3.19 +/- 1.61 pmol/l in those with stable angina, 3.58 +/- 1.92 pmol/l in those with unstable angina, 4.24 +/- 2.53 pmol/l in those with myocardial infarction. These values were not significantly different one another, nor from the values obtained from type 2 diabetic controls (3.64 +/- 2.13 pmol/l). In the non-diabetic patients, the mean Et-1 levels were 3.92 +/- 0.73 pmol/l in those with stable angina, 4.35 +/- 1.67 pmol/l in those with unstable angina, 4.33 +/- 1.66 pmol/l in those with myocardial infarction. These values were not significantly different one another, but significantly higher than those obtained from healthy controls (2.07 +/- 0.67 pmol/l; P < 0.001). No significant differences were found in Et-1 levels between diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction. In contrast, a statistically significant difference was found in Et-1 levels between diabetic and non-diabetic control subjects (P < 0.05). In conclusion, similar raised concentrations of Et-1 in diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction do not support the hypothesis that higher levels of Et-1 in diabetic patients are responsible for the increased incidence of CAD in diabetes mellitus. However, the raised Et-1 levels found in diabetic patients in the absence of CAD strongly suggest that a generalised endothelial dysfunction, documented in our study by increased levels of Et-1, most probably precedes subsequent cardiovascular diseases.

[Hypertension at the threshold of the year 2000: classification, treatment, prevention]. / La malattia ipertensiva alle soglie del 2000. Classificazione, trattamento, prevenzione.

Despite the clear benefits of treating established hypertension, this approach alone will not prevent all of the blood pressure-related cardiovascular-renal disease in the community. Primary prevention of hypertension is a natural extension of hypertension treatment which provides opportunity to reduce costly cycle of managing hypertension and its complications. The purpose of this report is to guide practician physicians and health professionals in their care of hypertensive patients. In order to provide specific guidelines, a new classification schema of high blood pressure that includes systolic as well diastolic levels is proposed (source, Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure 1993). Furthermore, recommendations for follow-up based on initial set of blood pressure measurements, life-style modifications and pharmacologic therapy are proposed, suggesting a new treatment algorithm in which diuretics and beta-blockers are preferred as first-choice agents because their confirmed reduction in morbidity and mortality (unless they are contraindicated or unacceptable), but including an expanded list of agents that are suitable for initial monotherapy and guidelines for selecting and individualizing the antihypertensive drug regimen.

Plasma levels of atrial natriuretic peptide and hemodynamic function in cardiac disease.

Plasma concentrations of atrial natriuretic peptide were measured in eight patients with cardiac disease but normal resting right atrial pressure, during cardiac catheterization. No patient had clinical evidence of overt heart failure. An increase in peptide concentrations was observed between the aorta or the peripheral vein and the pulmonary artery. A linear relation was found between peripheral vein and pulmonary artery peptide concentration. Mean pulmonary artery and capillary wedge pressure also correlated with the peptide levels. No correlation was observed between mean right atrial pressure and peptide concentration. These findings demonstrate that atrial natriuretic peptide release, even in the absence of cardiac failure, seems at least partly regulated by left atrial pressure. Finally, peripheral levels reflect the central concentrations of atrial natriuretic peptide.

Effects of moderate low sodium/high potassium diet on essential hypertension: results of a comparative study.

It is generally accepted that a significant restriction in sodium intake can lower blood pressure in hypertensive patients and more recently it has also been suggested that a high potassium intake can exert an antihypertensive effect. We have therefore, conducted a double-blind, randomized, cross-over study to evaluate the antihypertensive efficacy of the combination of a modest dietary sodium restriction and a high potassium intake in hypertensive patients of mild and moderate degrees. During the modest sodium (100 mmol/day)/high potassium (130 mmol/day) diet the blood pressure was significantly reduced (-17/-6 mmHg) when compared to the normal diet (160 mmol Na/day and 80 mmol K/day). The blood pressure reduction did not interfere with hemodynamic and humoral responses to dynamic exercise. The modest reduction in sodium intake and increase in potassium content in the diet was well tolerated by the patients.

Effects of dynamic exercise and metabolic control on left ventricular performance in insulin-dependent diabetes mellitus.

In subclinical diabetic cardiomyopathy, previous reports did not positively correlate the altered cardiac performance with metabolic parameters. Fifteen insulin-dependent diabetic subjects, without any clinical or instrumental evidence of heart diseases, were studied. Signs of diabetic microangiopathy were absent. Systolic time intervals, metabolic and hormonal parameters (blood glucose, free fatty acids, blood lactate and plasma norepinephrine) were evaluated at rest and after dynamic exercise during poor (MAGE 6.36 +/- 0.72 mmol/l) and good (MAGE 3.46 +/- 0.66 mmol/l) metabolic control, obtained by means of insulin therapy. Rest values of systolic time intervals were normal during poor and good metabolic control. After exercise, pre-ejection period/left ventricular ejection time ratio increased mainly during poor control as a result of an increased pre-ejection period: conversely, a smaller increase in pre-ejection period/left ventricular ejection time ratio occurred during good metabolic control. The exercise induced free fatty acids utilization did not occur during poor control as it occurred during good control. The percentage of increments in blood lactate was virtually identical in ketotic and non-ketotic patients and in normal subjects. High norepinephrine plasma levels were observed both at rest and during dynamic exercise in poorly controlled diabetic patients. Conclusively, testing of systolic time intervals after exercise might be useful in the detection of preclinical diabetic cardiomyopathy. The decreased cardiac functional reserve observed during poor control might be related to an altered energetic fuel utilization.

Metabolism of ecdysteroids during the vitellogenesis of the tick Ornithodoros moubata (Ixodoidea, Argasidae): accumulation of apolar metabolites in the eggs.

The fate of injected [3H]ecdysone [( 3H]E) and 20-hydroxy-[3H]ecdysone [( 3H]20E) has been investigated in the female tick Ornithodoros moubata (Murray, 1877; sensu Walton, 1962). When injected into fed mated vitellogenic females, [3H]E is converted into [3H]20E and two apolar classes of metabolites, AP1 and AP2. Injected [3H]20E is directly converted into AP1 and AP2. AP2 is incorporated into the ovaries in a high proportion and at the end of the vitellogenic cycle represents about 25% of the total label recovered from the animal. The fate of labeled hormones injected into virgin females which perform an abortive vitellogenic cycle is quite similar. However, the ovaries incorporated less of the AP2 products. Ovaries of mated females cultured in vitro in the presence of [3H]E are able to produce [3H]20E and AP2. AP2 is incorporated, while [3H]20E is mainly found in the medium. Ovaries of virgin females presented a slower rate of transformation and of incorporation of the label. Labeled AP2 is recovered in freshly laid eggs and AP1 in the females after oviposition. AP1 and AP2 can produce [3H]20E, [3H]E, and other minor polar peaks when submitted to hydrolysis by esterase. It is concluded that the female O. moubata possesses a special enzymatic mechanism for transformation of ecdysteroids into apolar products and for selective incorporation of AP2 into the ovaries. These products are present in the freshly laid eggs and could play a role during embryogenesis.