Physical activity and amyloid-ß plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing.

Previous studies suggest physical activity improves cognition and lowers Alzheimer's disease (AD) risk. However, key AD pathogenic factors that are thought to be influenced by physical activity, particularly plasma amyloid-ß (Aß) and Aß brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aß and amyloid brain deposition are associated with physical activity levels, and whether these associations differed between carriers and non-carriers of the apolipoprotein E (APOE) ε4 allele. Five-hundred and forty six cognitively intact participants (aged 60-95 years) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) were included in these analyses. Habitual physical activity levels were measured using the International Physical Activity Questionnaire (IPAQ). Serum insulin, glucose, cholesterol and plasma Aß levels were measured in fasting blood samples. A subgroup (n=116) underwent (11)C-Pittsburgh compound B (PiB) positron emission tomography (PET) scanning to quantify brain amyloid load. Higher levels of physical activity were associated with higher high density lipoprotein (HDL) (P=0.037), and lower insulin (P<0.001), triglycerides (P=0.019) and Aß1-42/1-40 ratio (P=0.001). After stratification of the cohort based on APOE ε4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aß from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ε4 carriers. Lower plasma Aß1-42/1-40 and brain amyloid was observed in those reporting higher levels of physical activity, consistent with the hypothesis that physical activity may be involved in the modulation of pathogenic changes associated with AD.

Combined liver kidney transplantation: critical analysis of a single-center experience.

Combined liver kidney transplantation (LKT) can be successfully performed on patients with liver and renal failure; however, outcomes are inferior to liver transplantation alone (OLT). Our aim was to determine the indications for and outcome of LKT and whether patients with longer wait times required more frequent LKT versus OLT alone. We included 18/93 adults who underwent LKT from August 2007 to August 2010 for hepatitis C virus (HCV, n = 7), alcohol (n = 5), nonalcoholic steatohepatitis (n = 2), primary biliary sclerosis, polycystic kidney disease with liver involvement, hepatic adenomatosis, and ischemic hepatitis. Eleven were originally listed for LKT and 7 required listing for-kidney transplantation while awaiting OLT. Eight were on dialysis when first listed and 10 had a low glomerular filtration rate or known kidney disease. The mean calculated Model for End-Stage Liver Disease (MELD) score for LKT was 31.2 ± 3.54. Seven had hepatocellular carcinoma in explants. Two patients had acute cellular kidney rejection that responded to treatment. Recurrence of HCV was documented in 5 patients within 6 months of LKT; 2/5 received HCV therapy (interferon and ribavirin) without renal allograft rejection. One-year liver graft/patient survival was 94% after LKT. One patient died at 6 months post LKT due to severe HCV recurrence. Last mean serum creatinine level was 1.35 ± 0.28 mg/dL for LKT patients. LKT is a safe procedure with favorable outcomes even in patients with a high MELD score. Transplantation of patients with a high MELD score due to regional variations in organ allocation results in additional use of kidneys by OLT patients. Improved organ allocation algorithms in OLT would help to reduce combined transplants, sparing more kidneys.

Successful treatment of fibrosing cholestatic hepatitis after liver transplantation.

BACKGROUND: A minority of liver transplant (OLT) recipients with hepatitis C virus (HCV) develop fibrosing cholestatic hepatitis (FCH), a severe form of HCV recurrence associated with early graft failure and death. There are few reports of successful salvage strategies. In this retrospective study, we sought to determine the characteristics and outcomes for patients with FCH at our transplant center. METHODS: All cases of HCV-positive OLT recipients from July 2007 through July 2010 were reviewed. Patient demographics, donor characteristics, and the post-OLT clinical course were analyzed. Tacrolimus-based immunosuppression was used. FCH was treated by conversion to cyclosporine A (CsA) and aggressive treatment with pegylated interferon (IFN) alpha2A and ribavirin (RBV). Liver biopsies and HCV RNA were obtained frequently per protocol or for cause. RESULTS: The rate of FCH during the study period was 13.5% (5/37). Of the 5 patients with FCH (4 males, 4 Caucasian), mean age was 51 (± 4.8) years and the Model for End-Stage Liver Disease (MELD) score at listing was 26.6 (± 10). Three of the 5 received liver and kidney (L/K) transplants (60%); the rate of L/K transplant in non-FCH patients was 12.5%. HCV RNA levels ranged from 5 to 6.69 log IU/mL pre-OLT; none were on anti-HCV therapy at the time of OLT. Mean ischemic time was 385 (± 152) minutes; donor age was 34.4 (± 13.7) years. No CMV infections developed postoperatively. Time to histologic HCV recurrence was 2 (± 2.23) months (range, 1-6); FCH occurred at 2.2 (± 2.2) months. Patients were converted from tacrolimus to CsA and treated with IFN and RBV; 2 were changed to consensus IFN. HCV RNA increased post-OLT in all, but responded to therapy in 4 of 5. None of the L/K recipients experienced renal graft rejection during treatment. Four of 5 had clinical and histologic improvement; 1 progressed to cirrhosis with minimal inflammation. One-year patient survival after OLT in this group was 80%. Liver allograft rejection occurred in 60% at 4.7 (± 5.5) months and was treated by CsA and prednisone dosage adjustments. In this cohort of patients undergoing OLT for HCV, FCH occurred early after OLT but responded to aggressive management with conversion from tacrolimus to CsA and treatment with pegylated IFN or consensus IFN/RBV. There was a higher rate of combined L/K transplants in the FCH group compared with the non-FCH group. Liver allograft rejection occurred in 60% of cases, but responded to treatment in all; no renal graft rejection occurred in the 3 with L/K transplants while on IFN. One-year graft and patient survival was 80%. CONCLUSION: Better survival with FCH is possible with early initiation of IFN/RBV therapy with close monitoring of biopsies and viral load, and conversion from tacrolimus to CsA. Treatment can be performed even in L/K transplantation recipients, although it is associated with a higher incidence of treatable liver allograft rejection.

The effect of insulin and glucose on the plasma concentration of Alzheimer's amyloid precursor protein.

The deposition of beta amyloid is a critical event in the pathogenesis of Alzheimer's disease. This peptide is a metabolite of the amyloid precursor protein. Recent research suggests that there is a correlation between plasma insulin and glucose concentrations and memory performance in Alzheimer's disease sufferers. Additionally, in vitro evidence suggests that both insulin and glucose may affect the metabolism of amyloid precursor protein and therefore the production of beta amyloid--however, to our knowledge no in vivo data have yet been published. We investigated the effect of elevated plasma levels of glucose and insulin on the plasma concentration of amyloid precursor protein in non-Alzheimer's disease subjects. As would be expected following ingestion of a glucose drink, blood insulin and glucose levels significantly increased. Interestingly, however, plasma amyloid precursor protein concentration decreased. Whilst no correlation was observed between insulin or glucose levels and plasma amyloid precursor protein concentration, the decrease in plasma amyloid precursor protein concentration was affected by the apolipoprotein E genotype of the subject. Possession of an epsilon4 allele resulted in a reduced decrease in plasma amyloid precursor protein in response to glucose ingestion when compared to non-epsilon4 subjects. We conclude that glucose ingestion, and the subsequent elevation of plasma levels of glucose and insulin leads to a decrease in plasma amyloid precursor protein concentration. Further studies are required to determine the clinical significance of these physiological changes in plasma amyloid precursor protein and the implications for Alzheimer's disease pathogenesis.

Case of Staphylococcus schleiferi endocarditis and a simple scheme to identify clumping factor-positive staphylococci.

Staphylococcus schleiferi is a coagulase-negative staphylococcus infrequently reported as a human pathogen. We report a case of prosthetic valve endocarditis attributed to this organism, contrast it to another Staphylococcus species that gives similar clumping factor results (S. lugdunensis), and propose a simple, effective identification scheme for identification of clumping factor-positive staphylococci.

[Worker turnover because of spinal pathologies in the wards and outpatient clinics of the hospitals of Leno and Manerbo, Brescia]. / Il turn-over, per patologie del rachide, dei lavoratori nei reparti di degenza e negli ambulatori degli ospedali di Leno e Manerbio (BS).

A total of 306 employees of the hospitals of the Leno/Manerbio health area underwent clinical and anamnestic examination in order to ascertain the existence of degenerative diseases of the spine associated with "manual handling of loads" risk. The prevalences obtained for positive anamnestic threshold concerning the lumbosacral spine, the trend of total acute low back pain and of low back pain in the last year showed lower values compared to the entire national group and in any case lower or only slightly above the values for the reference group of non-exposed subjects. Therefore, in order to assess the real prevalences of disorders due to incorrect load handling in hospital environments, it is important to assess the presence of associated disorders of the spine also and especially in outpatients departments. In fact, unsuitable or unfit staff had recently been transferred from the wards to outpatients departments. 56 workers from outpatients departments underwent physical-anamnestic examination: 16 workers (4.5% of the entire group under study) from average-to-high risk wards were identified as suffering from degenerative disorders of the lumbosacral spine. Therefore the prevalence of unfit subjects from hospital wards, cancelling the effect of the turnover factor on outpatients departments, led to an almost twofold total frequency, which rose from 6.9% to 11.4%.

Early out-of-hospital lidocaine administration decreases the incidence of primary ventricular fibrillation in acute myocardial infarction.

This study was designed to assess the effectiveness of early prehospital intravenous administration of lidocaine in preventing primary ventricular fibrillation (PVF) in patients with suspected acute myocardial infarction (AMI). Sixty patients with suspected AMI, seen by the Mobile Coronary Care Unit (MCCU) of Florence, were randomly allocated at home to treatment with lidocaine (bolus i.v. of 1 mg/kg, followed by an infusion of 4 mg/min) or placebo (infusion of saline at a rate of 1 mL/min), respectively. The lidocaine group (27 patients) and the control group (33 patients) were not significantly different in age, clinical condition, or time of randomization. The diagnosis of AMI was confirmed in all 60 patients during the hospital stay. Ventricular fibrillation (VF) occurred in 5 patients in the control group in comparison to none in the lidocaine group (P < 0.05). Three patients experienced VF at home and were successfully resuscitated by an MCCU cardiologist. In another two patients, VF occurred during the first 4 hours after onset of symptoms. No major side effects were observed after the infusion of lidocaine. Our findings support the effectiveness of the prophylactic administration of lidocaine in preventing PVF in the prehospital phase of AMI and suggest that the drug can be safely administered in this setting by prehospital personnel.

Out-of-hospital symptomatic supraventricular arrhythmias. Epidemiological aspects derived from 10 years experience of the Florence Mobile Coronary Care Unit.

The epidemiologic features and the relative incidence of symptomatic supraventricular tachycardias in out-of-hospital settings are unknown. Rhythm disturbances account for 20% of the interventions performed by the Florence Mobile Coronary Care Unit (MCCU). Between November 1979 and December 1989, the MCCU rescued 1239 patients with recent onset (less than 24 hours) symptomatic supraventricular arrhythmias. 809 had atrial fibrillation, 376 paroxysmal supraventricular tachycardia (PSVT), 36 atrial flutter and 18 different atrial dysrhythmias. Women showed an overall predominance, more evident in patients with PSVT, and the incidence of the arrhythmias increased with age. Preexisting heart disease was more frequent in atrial fibrillation (41.1%) and atrial flutter (33.4%) in comparison to PSVT (27.6%). Similarly, a higher incidence of associated cardiovascular events (AMI, acute coronary insufficiency, pulmonary edema) was found in patients with atrial fibrillation and atrial flutter. Palpitations were the main complaint in each group, however, in atrial fibrillation and atrial flutter they were frequently associated with chest pain or dyspnea.

Thrombin generation after physical exercise.

Many investigators have studied the influence of physical exercise on hemostatic system and it is well accepted that exercise causes an activation of coagulation as indicated by a shortening of aPTT and by an increase in plasma factor VIII activity and levels. A controversial point remains whether this clotting activation leads to a significant thrombin generation and fibrin formation. The type of physical exercise performed and the methods used to study blood coagulation may be two major sources of discrepancies in different studies. In the last years sensitive and reliable methods became available to evaluate prothrombin activation and thrombin generation. Thus in this study we have investigated the influence of a well standardized treadmill stress test, controlled by the measurement of cardiorespiratory and metabolic parameters, on plasma concentration of different markers of clotting activation in healthy untrained young subjects. Blood samples were also withdrawn just before anaerobic threshold to investigate a possible role of metabolic acidosis in changes of clotting system.

Automated blood pressure determination during exercise test. Clinical evaluation of a new automated device.

The accuracy and reproducibility of a new automatic device (P) specially designed for noninvasive blood pressure monitoring during the exercise stress test were evaluated in 50 consecutive subjects (34 normotensives and 16 hypertensives). Automatic measurements were compared with those taken by a sphygmomanometer (RR). A good agreement between systolic pressure values obtained by the two methods was found (RR 159 +/- 30 mmHg, P 158 +/- 28 mmHg, mean difference = -1.53 +/- 13 mmHg, p = 0.166, ns). On the contrary the new device significantly underestimated diastolic pressure values (RR 89.3 +/- 13 mmHg; P 84 +/- 13 mmHg, mean difference -5.37 +/- 9.3, p < 0.001). In conclusion the new device seems able to measure systolic but underestimates diastolic blood pressure both in hypertensives and in normotensives during the effort test.

Role of a prehospital medical system in reducing heroin-related deaths.

OBJECTIVE: The mortality rate from heroin overdose in Italy between 1977 and 1987 increased significantly. However, in the same period, a significant increase was not observed in Tuscany, an administrative region in Italy. This study was performed to determine if the prehospital emergency medical system of Florence, the capital of Tuscany (the only one operating in Italy during the study period), affected this lower mortality rate. DESIGN: Retrospective study. SETTING: The Florence system consists of 17 mobile ICUs, each of which is staffed by a physician and three paramedics. These units are able to carry out advanced cardiopulmonary resuscitation with equipment transported to the scene of an emergency. PATIENTS: A total of 126 consecutive patients with heroin overdose, assisted by four mobile ICUs from January 1, 1984 through December 31, 1987. INTERVENTIONS: Common therapeutic protocol in the treatment of heroin overdose and of cardiac arrest. RESULTS: Fifty-two (41.3%) patients were in respiratory arrest, and seven (5.6%) patients were in cardiorespiratory arrest. The prehospital mortality rate was 1.6%, the inhospital mortality rate was 0.8%, and the overall mortality rate was 2.4%. During the period considered, the number of heroin overdose-related interventions increased significantly, as did the number of heroin overdoses complicated by respiratory arrest or by cardiorespiratory arrest, but the mortality rate remained low. CONCLUSION: We suggest that an emergency medical system can play an important role in reducing the mortality rate from heroin overdose.

Diagnostic accuracy of peak exercise echocardiography in coronary artery disease: comparison with thallium-201 myocardial scintigraphy.

To evaluate the accuracy of exercise two-dimensional echocardiography for the recognition of coronary artery disease, 53 patients (46 men and 7 women, age range 35 to 69 years) without either previous myocardial infarction or resting wall motion abnormalities, were studied. According to coronary angiography 26 had normal coronary arteries, 14 had one-vessel, seven had two-vessel, and six had three-vessel disease. After withdrawal of any therapy, all patients underwent a single exercise stress test with a stress table during which cine-loop digitized echocardiography was acquired and 74 MBq of thallium-201 (TI-201) were injected. Echocardiographic images were evaluated at rest and at peak exercise. Three-view planar scintigraphic images were collected immediately after exercise and 4 hours later. For the overall recognition of coronary artery disease, exercise electrocardiography had 77.8% sensitivity and 65.4% specificity; myocardial scintigraphy had 100% sensitivity and 92.3% specificity; and exercise echocardiography had 92.6% sensitivity and 96.2% specificity (both NS versus myocardial scintigraphy). Global accuracy was 71.7% for exercise electrocardiography, 94.3% for stress echocardiography, and 96.2% for myocardial scintigraphy. For the classification of the individual involved coronary arteries, the sensitivity of myocardial scintigraphy was 84.8% and that of exercise echocardiography was 63% (p less than 0.01); the related specificities were 98% and 98.2% respectively (NS). It may be concluded that exercise echocardiography is highly accurate for the recognition of coronary artery disease, whereas it appears less sensitive in the identification of the involved vessels, particularly in patients with multivessel disease.

[Changes in the wall motion of left ventricle in dipyridamole-induced ischemic cardiopathy studied by nuclear magnetic resonance. A comparison with myocardial scintigraphy with 99mTc MIBI]. / Alterazioni della motilità parietale del ventricolo sinistro nella cardiopatia ischemica indotte da dipiridamolo studiate con risonanza magnetica nucleare. Confronto con la scintigrafia miocardica mediante 99mTc MIBI.

To investigate whether magnetic resonance imaging (NMR) can detect alterations in LV contractility during myocardial ischemia, ten patients aged 32-72 with coronary artery disease underwent ECG gated NMR performed at 0.5 Tesla after intravenous infusion of high dose dipyridamole (DP) (0.7 mg/Kg) over 5 minutes. LV contraction in planes similar to echo short axis projection was imaged under condition, 3' and 15-20' after infusion of DP by fast multiphasic imaging (FMI), multiple angulated cine-NMR sequence with a temporal resolution of 50 m/sec. Entity and size of perfusion defects after DP were determined by Tc 99m MIBI myocardial scintigraphy. In all patients changes in LV contractility appeared at NMR in the same site of perfusion impairments revealed with MIBI. In 8 patients the alterations lasted even more than 20' after the first NMR scan. NMR provides the opportunity of performing long-lasting assessment of ventricular wall contractility and enables to exactly localize the site and extension of kinetic changes as well as their time of onset and time duration.

Anaerobic threshold in patients with exercise-induced myocardial ischemia.

The aim of the present study was to investigate the ventilatory anaerobic threshold in patients with exercise-induced myocardial ischemia. Ventilatory volumes and gas exchanges were measured during treadmill stress testing in 36 patients (11 with previous myocardial infarction) with electrocardiographic criteria of myocardial ischemia during the test and in 23 healthy, untrained control subjects of equivalent age. The anaerobic threshold was detected in 32 of 36 patients (89%) and in 22 of 23 control subjects (96%). The anaerobic threshold was significantly lower in patients than in control subjects (13.5 +/- 1.9 versus 19.7 +/- 1.7 ml/kg per minute VO2, p less than 0.001). In the 21 patients without previous myocardial infarction, the anaerobic threshold was also significantly lower than in the control subjects (13.9 +/- 1.6 versus 19.7 +/- 1.7 ml/kg per minute VO2, p less than 0.001). Among the 21 patients without previous myocardial infarction, the 12 with a low ischemic threshold, which occurred during the first three steps of the modified Bruce protocol, had an anaerobic threshold significantly lower than the other nine patients (13.1 +/- 1.5 versus 14.9 +/- 1.0 ml/kg per minute VO2, p less than 0.01). However, even in the patients with a moderate to high ischemic threshold, the anaerobic threshold was significantly lower than in the control subjects (p less than 0.001). These data show that the anaerobic threshold can be measured in the great majority of patients with exercise-induced myocardial ischemia. The low anaerobic threshold level indicates a relevant functional impairment in these patients.

[The mobile coronary unit of Florence: an evaluation of 10 years of prehospital cardiac care]. / Unità coronarica mobile di Firenze: valutazione di dieci anni di cura cardiaca preospedaliera.

In order to reduce the high mortality from ischemic heart disease, a mobile coronary care unit manned by a cardiologist has been operating in Florence since 1979. From 1980 to 1989 there were 13,029 interventions, 8,718 (66.9%) of which were cardiac emergencies. 1,718 (19.7%) patients showed acute myocardial infarction while in 2,274 angina was diagnosed (26.1%). Acute pulmonary edema and paroxysmal supraventricular tachyarrhythmias accounted, respectively, for 6.2% and 18.3% of total cardiac emergencies; moreover there were 753 (5.8%) attempted resuscitations in sudden cardiorespiratory arrest from cardiac causes. In acute myocardial infarction, the median time between the onset of symptoms and mobile coronary care unit arrival was 85 minutes, and 69.9% of patients were reached within 3 hours from the onset of symptoms. Ventricular fibrillation, ventricular tachycardia and asystole were observed respectively in 80 (4.6%), 42 (2.4%) and 50 (2.9%) patients. Success rate of emergency treatment was 81.3% for ventricular fibrillation, 88.1% for ventricular tachycardia and 18% for asystole. Prehospital mortality was 4.06%. The ECG picture of the 753 patients found in cardiac arrest showed sustained ventricular tachycardia in 12 (1.6%), ventricular fibrillation in 198 (26.3%), bradyarrhythmia in 28 (3.7%), and asystole in 431 (57.2%). Cardiopulmonary resuscitation was successfully performed in 230 patients (30.5%). Finally, more than 50% of the patients with angina, 20% of the patients with acute pulmonary edema, and 70% of the patients with paroxysmal supraventricular tachyarrhythmia were adequately treated at home and needed no hospitalization. The ten years experience of Florence Mobile Coronary Care Unit suggests that a community wide emergency cardiac care system can significantly reduce the pre-hospital mortality and the time delays preceding thrombolysis and intensive care in acute myocardial infarction. Moreover, the cardiac "sudden death" can often be successfully treated. Most other cardiac emergencies may be adequately treated at home and unnecessary hospitalizations can be avoided.

Evaluation of a mobile coronary care unit protocol in patients with acute onset chest pain.

This study was designed to assess the accuracy of a diagnostic protocol of the mobile coronary care unit (MCCU) of Florence for acute chest discomfort. During 1986, 706 patients with chest pain were seen by the MCCU. Of these, 324 of 376 (95.2%) of those hospitalized and 247 of 324 (76.2%) of the nonhospitalized patients were entered in the study. The MCCU diagnosis of acute myocardial infarction (AMI) was confirmed in 120 patients (80.3%). A false positive diagnosis of AMI was made in 27 patients (6.9%), while in 37 patients AMI was not diagnosed at the first MCCU clinical examination (false negative). The sensitivity in the diagnosis of AMI was 80.5%, the specificity 91.8%, and the diagnostic accuracy 89.1%. In the recognition of acute coronary syndromes (AMI + unstable angina), sensitivity and specificity were, respectively, 94.0% and 94.4%. The protocol of the Florence MCCU provides high accuracy in the diagnosis of AMI and acute coronary insufficiency; close adherence to the protocol can decrease the number and the costs of undue hospital admissions while protecting the safety of patients.

Neuropsychological outcome of survivors of out-of-hospital cardiac arrest.

Thirty patients resuscitated from out-of-hospital cardiac arrest (15 with and 15 without postanoxic coma on admission) underwent a clinical examination and neuropsychological testing. In order to assess quality of life, they were compared to two matched control groups; 15 patients with previous myocardial infarction and 15 healthy subjects. None of the survivors showed severe neurologic impairment, and all had returned to self-sufficient physical activity. However, the behavior rating scale scores were significantly worse in patients with postanoxic coma. The processing ability linked to memory was significantly worse in the postanoxic coma group. Mood disorders were also observed in this group, but they did not have pathological significance. The remarkably low incidence of neurologic and psychological sequelae in these resuscitated patients, particularly in those with early clinical evidence of severe cerebral damage, is an encouraging result that supports the therapeutic systems development and efforts in the management of out-of-hospital cardiac arrest.