Biomedical subjects

A A Mangoni

Publications and source records attributed to A A Mangoni.

At least 19 recordsLinked to original sources

PubMed2006

Hypertension and sensorimotor peripheral neuropathy in type 2 diabetes.

BACKGROUND: The mechanisms responsible for the onset of sensorimotor peripheral diabetic neuropathy (SMPN) remain largely unknown. To address this issue, we studied the relationship between traditional cardiovascular risk factors, parameters of metabolic control, and the presence of SMPN in patients with type 2 diabetes of relatively short duration. METHODS: Blood pressure, glycated hemoglobin, lipid profile, and the presence of micro- and macrovascular complications were assessed and monitored in 31 consecutive ambulatory patients with type 2 diabetes (age 60.7 +/- 7.5 years, mean +/- SD) within 10 years of diagnosis (mean diabetes duration 6.0 +/- 2.3 years). RESULTS: Clinical and neurophysiological features of SMPN were present in 10 patients (SMPN+, 32%). There were no significant differences in age, gender distribution, diabetes duration, body mass index, metabolic control, and serum cholesterol between SMPN- and SMPN+ patients. However, the prevalence of hypertension (i.e. blood pressure >/=140/90 mm Hg) was higher in SMPN+ patients (10/10 vs. 13/21, chi(2 =) 5.13, p = 0.025). Regression analysis showed that, after correcting for age, gender, duration of diabetes, glycated hemoglobin, and cholesterol, the presence of hypertension was independently associated with SMPN (R(2) = 0.17, p = 0.023). CONCLUSIONS: There is a strong association between hypertension and SMPN in type 2 diabetic patients with relatively short duration of disease. This relationship is independent of other risk factors.

Age of Onset↗

PubMed2006

The implications of a growing evidence base for drug use in elderly patients. Part 1. Statins for primary and secondary cardiovascular prevention.

Although elderly patients represent a rapidly growing population often requiring multiple drug treatment, the evidence of effectiveness is limited for many interventions and therapies in this age group. Only during the last 30 years has a requirement to incorporate evidence into the treatment of older subjects become part of the pre- and postmarketing regulatory process in Europe and the United States. Recently, elderly patients have been shown to benefit comparably from several treatments. These studies have supported the validity of an increasingly interventional approach to disorders common in late life. However, an important issue is the applicability of the growing body of clinical trials to 'real life' patients. This is particularly true in very old (i.e. >80 years) patients and those with significant comorbidities. We review the current evidence and controversies related to the effectiveness and safety of several therapeutic strategies in cardiovascular disease (i.e. statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-adrenoceptor blockers, and thrombolytic agents) and bone health (i.e. vitamin D and bisphosphonates).

Adult↗

PubMed2006

The implications of a growing evidence base for drug use in elderly patients Part 2. ACE inhibitors and angiotensin receptor blockers in heart failure and high cardiovascular risk patients.

Traditionally, angiotensin converting enzyme (ACE) inhibitors have been used for the management of patients with congestive cardiac failure. Studies performed over the last decade have demonstrated that (1) angiotensin receptor blockers (ARBs) are as effective as ACE inhibitors in reducing morbidity and mortality in cardiac failure; and (2) inhibition of the renin-angiotensin system provides beneficial effects in patients at high cardiovascular risk without cardiac failure. This review focuses on the applicability of the results of the main trials with ACE inhibitors and ARBs to the elderly population.

Age Factors↗

PubMed2006

The implications of a growing evidence base for drug use in elderly patients. Part 3. Beta-adrenoceptor blockers in heart failure and thrombolytics in acute myocardial infarction.

Beta-adrenoceptor blockers and thrombolytic agents are of established value in the pharmacological management of heart failure and ST-elevation myocardial infarction, respectively. However, there is uncertainty as to whether these therapeutic strategies can be safely and effectively adopted in elderly patients with comorbidities, particularly in old-old individuals. This review focuses on these trials and the age-related efficacy and safety of these drugs.

Adrenergic beta-Antagonists↗

PubMed2006

The implications of a growing evidence base for drug use in elderly patients. Part 4. Vitamin D and bisphosphonates for fractures and osteoporosis.

Fractures are common in elderly subjects, disabling and occasionally fatal. Their incidence increases exponentially with age, with the commonest affected sites being the wrist, vertebrae, hip and humerus. Of these, hip fractures are the most relevant in terms of morbidity and financial cost. The increase in fracture rate with age is believed to result predominantly from age-related increases in the incidence of osteoporosis and falls. This article reviews the evidence for the use of vitamin D and bisphosphonates for the prevention of bone fractures and osteoporosis in elderly patients.

Accidental Falls↗

PubMed2006

Effect of methionine loading on pulse wave analysis in elderly volunteers.

OBJECTIVE: To test the hypothesis that an acute increase in plasma homocysteine produced by methionine is associated with an acute increase in pulse wave velocity. DESIGN: A double blind, cross over, placebo controlled design was used and pulse wave velocity, plasma homocysteine, total cholesterol: high density lipoprotein ratio, plasma triglyceride, oxidised low density lipoprotein cholesterol concentrations, apolipoproteins A1 and B, and C reactive protein were measured between 12.5 and 20 hours after methionine loading or placebo. RESULTS: Between 12.5 and 20 hours after exposure to a methionine loading test, arterial pulse wave velocity showed no significant difference compared with placebo. At 12 hours after exposure to the methionine loading test, in the presence of a controlled diet, triglyceride concentration significantly increased by 32.6% (p<0.02), cholesterol: high density lipoprotein ratio increased significantly by 22.5% (p<0.05) compared with placebo. Simultaneously, systolic blood pressure increased significantly by 4.9% (p<0.02). CONCLUSION: In elderly volunteers, acute hyperhomocysteinaemia induced by methionine loading resulted in no overall significant delayed reduction in peripheral arterial distensibility. A significant deterioration in the lipid profile and increased blood pressure was seen during acute hyperhomocysteinaemia.

Aged↗

PubMed2006

Predictors of impaired blood pressure homeostasis during acute and sustained orthostasis in patients with type 2 diabetes.

AIM: Sympathetic failure with acute postural hypotension is a common feature of advanced autonomic neuropathy in type 2 diabetes. It is unknown, however, whether: a) the presence of sympathetic autonomic neuropathy is also a powerful predictor of postural blood pressure changes during sustained orthostasis and b) other factors affecting baroreceptor and neuro-hormonal control might play a role. METHODS: Systolic blood pressure (SBP) was measured during supine rest and after 2, 5, and 20 min of active orthostasis in 45 males with type 2 diabetes (age 56.4+/-8.2 years, mean+/-SD) and different degrees of autonomic neuropathy (absence of neuropathy, n=26, parasympathetic neuropathy, n=9, and sympathetic neuropathy, n=10). Eight healthy subjects (50.1+/-11.6 years) served as controls. A multiple backward regression analysis was performed to identify independent predictors of SBP changes during orthostasis. The regression model included presence/absence of sympathetic autonomic neuropathy, age, diabetes duration, presence/absence of hypertension, baseline SBP and neuro-hormonal parameters (plasma adrenaline, noradrenaline, plasma renin activity, and aldosterone). RESULTS: Sympathetic autonomic neuropathy (P=0.005), baseline SBP (P=0.001), and adrenaline (P=0.003) independently predicted SBP changes after 2 min (R2=0.64); sympathetic autonomic neuropathy (P<0.001), baseline adrenaline (P=0.008), and plasma renin activity (P=0.006) predicted SBP changes after 5 min (R2=0.58); whereas sympathetic autonomic neuropathy (P<0.001) and baseline SBP (P<0.001) predicted SBP changes after 20 min orthostasis (R2=0.65). CONCLUSIONS: The presence of sympathetic autonomic neuropathy and higher supine SBP values remain strong and independent predictors of SBP fall not only during the acute transition from supine to standing position but also during sustained orthostasis in type 2 diabetes. Lower baseline plasma adrenaline concentrations and plasma renin activity are also involved, though to a lesser extent, in the genesis of this haemodynamic response.

Blood Pressure↗

PubMed2005

Profound weight loss associated with reboxetine use in a 44-year-old woman.

We report a case of significant weight loss experienced by a 44-year-old Caucasian woman treated with reboxetine. She was treated with this drug at 12 mg daily for a total duration of 11 months. During the corresponding period her body mass index (BMI) decreased from a baseline of 21.4 kg m(-2) to a low of 16.8 kg m(-2). Withdrawal of the drug led to a full recovery of her BMI. The strongest evidence linking reboxetine to this woman's weight loss laid in the fact that the re-introduction of the drug subsequently caused a similar negative impact in her BMI.

Adrenergic Uptake Inhibitors↗

PubMed2005

Pulse pressure is independently associated with sensorimotor peripheral neuropathy in patients with type 2 diabetes.

OBJECTIVES: The mechanisms responsible for the onset and progression of sensorimotor peripheral neuropathy (SMPN) in type 2 diabetes remain largely unknown. Although a link between hypertension and SMPN has been observed, it is not clear which blood pressure (BP) component (i.e. systolic, SBP; diastolic, DBP; or pulse pressure, PP) is primarily involved. We sought to determine the relationship between BP components and parameters of nerve function in type 2 diabetes. DESIGN: Cross-sectional study. SETTING: Academic medical centre. SUBJECTS: A total of 55 consecutive ambulatory patients with type 2 diabetes (age 62.6 +/-8.0 years, mean +/- SD). INTERVENTIONS: Measurement of clinic BP and 10 neurophysiological parameters: motor nerve conduction velocity (NCV; median, ulnar, posterior tibial and peroneal nerve), sensory amplitude (AMP) and latency (LAT; median, ulnar and sural nerve). RESULTS: Univariate analysis showed that age, diabetes duration, SBP and PP were negatively correlated with nerve function. Regression analysis showed that, after correcting for age, duration of diabetes, glycated haemoglobin, body mass index, microalbuminuria and SBP, PP was independently and negatively associated with NCV (median, P =0.011; ulnar, P = 0.001; peroneal, P = 0.006 and posterior tibial, P = 0.005) and signal AMP (ulnar, P = 0.027; sural, P = 0.055), and positively associated with signal LAT (median, P = 0.083; sural, P = 0.021). SBP was negatively associated with signal AMP (median, P = 0.012) and positively associated with LAT (ulnar, P = 0.018). By contrast, DBP failed to show any significant correlation with nerve function. CONCLUSIONS: The PP is strongly associated with neurophysiological parameters of nerve function in patients with type 2 diabetes. This relationship is independent of traditional risk factors and other BP components.

Age Factors↗

PubMed2004

Stroke, dementia, and drug delivery.

Stroke and dementia represent a major health burden for elderly subjects as they are associated with significant morbidity and mortality. The rates of stroke and dementia are progressively increasing due to the ageing population in most westernized countries. Therefore, both these conditions represent a major therapeutic target. However, the therapeutic options available for the management of stroke and dementia remain largely unsatisfactory, the main reason being the difficulty in transferring the results obtained in animal and in vitro studies to the clinical setting. This review focuses on the recent advances in pathophysiology and treatment of these conditions and future directions for research. Moreover, the technique of functional magnetic resonance imaging is discussed in detail as a tool to assess the effects of therapeutic agents on the central nervous system and monitor the progression of diseases. Finally, an overview of the issue of drug delivery into the central nervous system is presented.

Anticholesteremic Agents↗

PubMed2004

Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications.

Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiological stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.

Aging↗

PubMed2004

Optimization of drug prescribing.

The hazards of prescribing many drugs, including side-effects, drug interactions, and difficulties of compliance, have long been recognized as particular problems when prescribing for elderly people. The need for appropriate and rational prescribing for elderly patients has been prioritized in the National Service Framework for Older People. This review addresses the research evidence on epidemiology of prescribing in elderly patients, methods of measuring the quality, and the role of the prescriber and the multidisciplinary team in the day-to-day optimization of drug therapy.

Aged↗

PubMed2003

The cardiovascular system.

The ageing process is associated with important changes in the responses of the cardiovascular system to pharmacological stimuli. They are not limited to the arterial system, involved in the modulation of cardiac afterload and vascular resistance, but they also involve the low-resistance capacitance venous system and the heart. The main changes include loss of large artery compliance, dysfunction of some of the systems modulating resistance vessel tone, increased activity of the sympathetic nervous system, and reduced haemodynamic responses to inotropic agents. This review focuses on the effects of ageing on arterial and venous reactivity to drugs and hormones, the autonomic nervous system, and the cardiovascular responses to inotropic agents. Some of the age-related changes might be at least partially reversible. This may have important therapeutic implications.

Aging↗

PubMed2003

Relative preservation of the renin-angiotensin-aldosterone system response to active orthostatism in type 2 diabetic patients with autonomic neuropathy and postural hypotension.

OBJECTIVE: The pathophysiological mechanisms involved in the progression of autonomic neuropathy (AN) and development of postural hypotension (PH) in type 2 diabetes (T2D) are largely unknown. The aim of this study was to address this issue by investigating the neurohormonal responses during active orthostatism (O) in T2D patients with and without PH. METHODS: Plasma noradrenaline (NA, pmol/L), adrenaline (A, pmol/L), plasma renin activity (PRA, angiotensin I, nmol/L/h) and aldosterone (ALD, pmol/L) were measured in the supine position (baseline) and after 2, 5, and 20 min O in 10 healthy subjects (C), 9 T2D patients without AN (D), 14 T2D patients with AN and without PH (DAN), and 7 T2D patients with AN and PH (DAN-PH). RESULTS: NA concentrations were significantly increased in the C. D and DAN groups during O. In the DAN-PH group, NA increased less markedly with no significant changes at 20 min O (+ 354 +/- 89 pmol/L at 2 min, p < 0.05; + 756 +/- 171 at 5 min, p < 0.05; + 656 +/- 295 at 20 min, p = NS). Absolute NA increments in the DAN-PH group were significantly lower than those in the C, D and DAN groups at 2 and 20 min. Concentrations of A increased significantly in the C and D groups whereas no significant changes were observed in the DAN (+ 27 +/- 27 pmol/L at 2 min, p = NS: + 22 +/- 22 at 5 min, p = NS; + 76 +/- 33 at 20 min, p = NS) and DAN-PH group (+ 16 +/- 11 pmol/L at 2 min, p = NS: + 71 +/- 27 at 5 min, p = NS; + 76 +/- 22 at 20 min, p = NS). Absolute A increments in the DAN and DAN-PH groups were significantly lower than those in controls at 2 and 20 min. By contrast, PRA and ALD increased significantly in all four groups. Absolute PRA increments were similar across the four groups, whereas ALD increments in the D, DAN and DAN-PH groups were significantly lower than those in the C group. CONCLUSIONS: In the DAN-PH group, the renin-angiotensin-aldosterone system response to O was relatively preserved compared with A and NA responses. The impairment of NA response was limited to the DAN-PH group, whereas the reduced A response was a feature of DAN regardless of PH.

Aldosterone↗

PubMed2003

An unusual case of pneumonia.

A previously healthy 37-year-old man was admitted with a two-month history of increasing shortness of breath and high temperature. A chest X-ray demonstrated bibasal shadowing and small bilateral pleural effusions; arterial blood gases demonstrated low pO2. Despite intravenous antibiotics no significant improvement was observed. A high-resolution chest computed tomography showed diffuse ground-glass opacification with segmental and subsegmental airways opacification, indicating fine fibrosis. Subsequently, open lung biopsy showed diffuse alveolar damage and a histopathological diagnosis of acute interstitial pneumonia (Hamman-Rich syndrome) was made. Antibiotics were stopped and high intravenous doses of steroids were given with a dramatic improvement in the patient's breathing and radiographic findings. The pathophysiological mechanisms of acute interstitial pneumonia and current therapeutic options are discussed.

Adult↗

PubMed2003

High rate of neoplasia and other co-morbid conditions in type-2 diabetic patients with longer duration of disease and poor metabolic control.

AIM: The aim of the study was to assess the rate of neuroendocrine malignancies in the gastrointestinal tract, other malignancies and mitotic processes, in type-2 diabetic patients. In particular, we tested the hypothesis that a poor metabolic control is associated with a higher rate of neoplasms and other co-morbid conditions, such as hypertension and peripheral neuropathy. METHODS: Forty-one consecutive asymptomatic type-2 diabetic outpatients were followed for 8 years and clustered in 2 groups, according to disease duration, insulin need, and dose of oral antidiabetic agents. Physical examination, blood pressure measurements, and neurophysiologic studies were serially performed during the follow-up. In each subject, a general biochemistry was performed, aspecific and specific antigens (alpha-fetoprotein, carcinoembrionic-antigen and prostate specific antigen PSA and F-PSA) levels were measured, and invasive and non-invasive procedures were carried out, when necessary, to detect a neoplastic process. RESULTS: The rate of malignancies and mitotic processes was significantly higher in patients with longer duration of disease and poor diabetes control (72% vs 13%, p=0.02). Hypertension (83% vs 54%) and peripheral neuropathy (67% vs 21%) were also more common in this group. CONCLUSION: These data, although obtained in a relatively small population, highlight the importance of closely monitoring type-2 diabetic patients with poor diabetes control as this might be associated with the presence of malignancy or other co-morbid conditions. This may be particularly true when the poor glycemic control is characterised by a sudden onset or significant worsening despite streghtening of antidiabetic therapy.

Adult↗

PubMed2002

Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial.

OBJECTIVE: Cigarette smoking is associated with increased plasma homocysteine concentrations, endothelial dysfunction and arterial stiffening. Homocysteine per se induces endothelial dysfunction and arterial stiffening and might account, at least partly, for the vascular abnormalities observed in smokers. We sought to determine whether folic acid supplementation, by reducing plasma homocysteine concentrations, enhanced endothelial function and reduced arterial stiffness in smokers. DESIGN: Double-blind, randomized controlled, parallel-group, trial. SETTING: Academic medical centre. SUBJECTS: A consecutive sample of 24 healthy cigarette smokers (age 37.8 +/- 2.5 years, mean +/- SEM). INTERVENTION: Subjects were randomly assigned to 4-week folic acid 5 mg day-1 or placebo. MAIN OUTCOME MEASURES: The following were measured before and after treatment: (i) peripheral vasoreactivity (forearm arterial blood flow, FABF) during intra-arterial administration of endothelium-dependent (acetylcholine 1.5, 4.5 and 15 microg min-1) and endothelium-independent (sodium nitroprusside 1, 2 and 4 microg min-1) vasodilators; (ii) carotid-femoral pulse-wave velocity (PWV); (iii) blood pressure (BP). RESULTS: Folic acid reduced homocysteine concentrations (10.8 +/- 0.6 vs. 8.2 +/- 0.5 micromol L-1, P < 0.001) and enhanced endothelium-dependent vasodilatation during each acetylcholine infusion rate (ratio between the FABF in the infused and control arm during increasing infusion rates at baseline 1.09 +/- 0.03 vs. 1.41 +/- 0.09 after treatment, P < 0.01; 1.39 +/- 0.07 vs. 1.83 +/- 0.12, P < 0.01; 1.65 +/- 0.16 vs. 2.72 +/- 0.36, P < 0.05) whilst endothelium-independent vasodilatation was unaffected. A significant fall in BP was also observed (mean BP 88 +/- 2 vs. 83 +/- 1 mmHg, P < 0.01). By contrast, PWV did not significantly change (8.4 +/- 0.3 vs. 7.8 +/- 0.4 m s-1). No significant changes in plasma homocysteine concentrations, FABF, BP, and PWV were observed in the placebo group. A multiple regression analysis showed that changes in folic acid plasma concentrations independently predicted both FABF changes during maximal acetylcholine-mediated vasodilatation (P < 0.01) and BP changes (P = 0.01). CONCLUSIONS: Short-term folic acid supplementation significantly enhanced endothelial function and reduced BP in young chronic smokers. These effects were largely independent from the homocysteine lowering effects. Thus, a simple, nontoxic, and relatively inexpensive vitamin intervention might be useful in primary cardiovascular prevention in this high-risk group.

Adult↗

PubMed2001

Outcome following isolated tricuspid valve replacement.

OBJECTIVES: The clinical outcome of isolated tricuspid valve replacement is not well defined because this procedure is usually performed concomitantly with other valve surgery. METHODS: We retrospectively studied the short and long-term outcome of 15 consecutive patients (six men and nine women, aged 61+/-3 years) undergoing isolated tricuspid valve replacement from 1984 to 1996. The cause of valve dysfunction was rheumatic heart disease in 12 patients, healed endocarditis in two patients, and sarcoidosis in one patient. The tricuspid valve was stenotic in one patient, regurgitant in eight patients, and both stenotic and regurgitant in six patients. A St. Jude Medical prosthesis was placed in eight patients, Carpentier-Edwards in five patients, and Björk-Shiley and Starr-Edwards in one patient each. RESULTS: The median survival was only 1.2 years. Three patients (20%) died < or =30 days after the surgery or before discharge, and six other patients (40%) died within 3 years of surgery. Anasarca was the only predictor of short-term mortality (P=0.03), while the predictors of long-term mortality were anemia (P=0.01), rheumatic heart disease (P=0.04), previous stroke (P=0.04), and previous mitral valve surgery (P=0.04). CONCLUSIONS: Isolated tricuspid valve replacement is characterized by a poor short and long-term outcome.

Adult↗