The role of skin biopsy in differentiating small-fiber neuropathy from ganglionopathy.

BACKGROUND AND PURPOSE: We aimed to test the clinical utility of the leg:thigh intraepidermal nerve-fiber (IENF) density ratio as a parameter to discriminate between length-dependent small-fiber neuropathy (SFN) and small-fiber sensory ganglionopathy (SFSG) in subjects with signs and symptoms of small-fiber pathology. METHODS: We retrospectively evaluated thigh and leg IENF density in 314 subjects with small-fiber pathology (173 with distal symmetrical length-dependent SFN and 141 with non-length-dependent SFSG). A group of 288 healthy subjects was included as a control group. The leg:thigh IENF density ratio was calculated for all subjects. We used receiver operating characteristic curve analyses to assess the ability of this parameter to discriminate between length-dependent SFN and SFSG, and the decision curve analysis to estimate its net clinical benefit. RESULTS: In patients with neuropathy, the mean IENF density was 14.8 ± 6.8/mm at the thigh (14.0 ± 6.9/mm in length-dependent SFN and 15.9 ± 6.7/mm in patients with SFSG) and 7.5 ± 4.5/mm at the distal leg (5.4 ± 3.2/mm in patients with length-dependent SFN and 10.1 ± 4.6/mm in patients with SFSG). The leg:thigh IENF density ratio was significantly (P < 0.01) lower in patients with length-dependent SFN (0.44 ± 0.23) compared with patients with SFSG (0.68 ± 0.28). The area under the curve of the receiver operating characteristic analysis to discriminate between patients with length-dependent SFN and SFSG was 0.79. The decision curve analysis demonstrated the clinical utility of this parameter. CONCLUSIONS: The leg:thigh IENF ratio represents a valuable tool in the differential diagnosis between SFSG and length-dependent SFN.

A multi-center, multinational age- and gender-adjusted normative dataset for immunofluorescent intraepidermal nerve fiber density at the distal leg.

BACKGROUND AND PURPOSE: Quantification of intraepidermal nerve fibers (IENFs) in skin biopsies is now the tool of choice to diagnose small fiber neuropathies. An adequate normative dataset, necessary to assess normality cutoffs, is available for brightfield microscopy but not for immunofluorescence. METHODS: Intraepidermal nerve fiber density data in distal leg skin samples processed with immunofluorescence were collected from 528 healthy individuals from four experienced laboratories worldwide. In all laboratories skin samples were collected, processed and analyzed according to standard procedures. Quantile regression analysis was employed to tailor the fit of the 5° percentile as the normal cutoff value and to test and measure the effect of age, gender, body mass index, race, biopsy site (lateral distal lower leg or medial posterior mid-calf) and participating laboratory as possible influential variables. RESULTS: Age, gender and biopsy site showed an independent linear correlation with IENF density. For each decade the 5° quantile IENF cutoff showed a 0.54 fibers/mm decrease, whilst females exhibited a 1.0 fiber/mm cutoff greater than males. Compared to the lateral distal lower leg, biopsies from the calf showed a 3.4 fibers/mm lower 5° percentile cutoff, documenting a variation linked by site. CONCLUSIONS: An age- and gender-adjusted normative dataset for IENF density at the lateral distal lower leg obtained with indirect immunofluorescence is presented for the first time by sharing data from four experienced laboratories worldwide. This dataset can be used as reference for laboratories processing skin biopsies with this technique.

UCP1 -3826 AG+GG genotypes, adiponectin, and leptin/adiponectin ratio in severe obesity.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are well-recognized complications of obesity. This study was designed to evaluate the role of the UCP1 -3826 A>G polymorphism, adiponectin levels, leptin/adiponectin ratio (L/A), and main biochemical parameters in 102 unrelated severely obese adults [61 females and 41 males, median body mass index (BMI) = 47.8 kg/m2] with NAFLD, with (MS+) or without MS (MS-) from Southern Italy. SUBJECT AND METHODS: The UCP1 polymorphism was tested by the TaqMan method, main biochemical parameters by routinary methods, adiponectin, and leptin serum levels by enzyme-linked immunosorbent assay. MS was diagnosed according to the American Heart Association criteria, liver steatosis was detected by ultrasound. RESULTS: MS was present in 53% male and 66% female obese patients. Only total cholesterol (p=0.04 males and p=0.002 females) and L/A ratio (p=0.03 males) differed between MS+ and MS- obese patients. At multivariate analysis, severe liver steatosis was significantly associated with: UCP1 (AG+GG) genotypes [odds ratio-confidence interval (OR-CI): 4.25; 1.12-16.13], MS (OR-CI: 8.47; 1.78-40.25), low adiponectin levels (OR-CI: 0.92; 0.87-0.98), high alanine aminotransferase levels (OR-CI: 1.03; 1.00-1.06), age (ORCI: 1.08; 1.00-1.15), and male gender (OR-CI: 10.78; 1.61- 71.96). CONCLUSION: In addition to traditional factors, total cholesterol and L/A ratio appear to contribute to MS characterization in severe obesity. Furthermore, the UCP1 (AG+GG) genotypes and low adiponectin levels could predispose to a more severe liver steatosis independently of MS presence. Based on our data, polymorphic UCP1 (AG+GG) obese patients with low adiponectin levels appear to be high-risk subjects for worsening of liver steatosis, a NAFLD, possibly requiring a second-step evaluation by liver biopsy.

Vascular risk factors in mild cognitive impairment subtypes. Findings from the ReGAl project.

BACKGROUND AND AIM: To investigate the role of vascular risk factors in different subtypes of mild cognitive impairment (MCI) in a multicentric, clinic-based, cross-sectional study. METHODS: Two-hundred and seven subjects with MCI were included in the study: 33 with single non-memory MCI (snmMCI), 42 with multiple-domain amnestic MCI (mdMCI-a) and 132 with amnestic MCI (aMCI). Several clinical vascular risk factors and magnetic resonance imaging (MRI) brain lesions were evaluated. RESULTS: snmMCI showed a higher frequency of ischaemic heart disease and of transient ischaemic attack (TIA)/stroke, a higher Hachinski ischaemic score and a higher frequency of white-matter lesions on MRI compared to aMCI. Subjects with mdMCI-a showed clinical characteristics similar to aMCI, except for a higher frequency of a history of TIA/stroke. CONCLUSION: Our findings suggest that snmMCI may be considered a vascular cognitive disorder.

Polymorphism p.402Y>H in the complement factor H protein is a risk factor for age related macular degeneration in an Italian population.

AIMS: To evaluate the complement factor H (CFH) p.402Y>H polymorphism as a risk factor in age related macular degeneration (AMD) in an Italian population. METHODS: 104 unrelated Italian AMD patients and 131 unrelated controls were screened for the CFH polymorphism p.402Y>H (c.1277 T>C), which has been associated with AMD. Retinography was obtained for patients and controls; the AMD diagnosis was confirmed by fluorescein angiograms. The c.1277 T>C polymorphism was genotyped with the TaqMan real time polymerase chain reaction single nucleotide polymorphism assay. RESULTS: The frequency of c.1277C allele was higher in AMD patients than in controls (57.2% v 39.3%; p<0.001). The odds ratio (OR; logistic regression analysis) for AMD was 3.9 (95% confidence interval (CI): 1.9 to 8.2) for CC homozygotes. The CC genotype conferred a higher risk for sporadic (OR 4.6; CI: 2.0 to 10.5) than for familial AMD (OR 2.9; CI: 1.0 to 8.4). Genotypes were not related to either age at AMD diagnosis or to AMD phenotype. However, geographic atrophy and choroidal neovascularisation were more frequent in sporadic than in familial AMD (p = 0.027). Overall, the percentage of population attributable risk for the CC genotype was 28% (95% CI:18% to 33%). CONCLUSION: The association between the p.402Y>H (c.1277T>C) polymorphism and AMD applies to the Italian population and the CC genotype is more frequent in sporadic than in familial AMD cases.

Effects of aging on asynchronous left ventricular regional function and global ventricular filling in normal human subjects.

In many patients with coronary artery disease or hypertrophic cardiomyopathy, reduced left ventricular rapid diastolic filling is related to asynchronous left ventricular regional diastolic function. Because left ventricular filling also declines with aging in normal subjects, in this study the influence of regional ventricular diastolic asynchrony on global ventricular filling as a function of age was investigated in 66 normal volunteers aged 19 to 77 years (mean 42) by radionuclide angiography. No subject had systemic hypertension or left ventricular hypertrophy. Indexes of left ventricular systolic function at rest did not vary with age, but rapid diastolic filling significantly declined with age: peak filling rate decreased (r = 0.69), time to peak filling rate increased (r = 0.53) and magnitude of rapid filling (% of left ventricular end-diastolic volume) decreased (r = 0.76) with aging. Left ventricular synchrony was assessed from regional volume curves derived by dividing the global ventricular region of interest into four quadrants. Indexes of systolic synchrony were unaffected by age, but regional variation in time to peak filling rate, an index of diastolic asynchrony, increased with aging (r = 0.51, p less than 0.001). Moreover, variation in time to peak filling rate correlated with global peak filling rate and magnitude of rapid filling (r = 0.48 and 0.54, p less than 0.001 for both). Multivariate analysis indicated that these effects were independent of age-related changes in blood pressure. Thus, aging alters left ventricular diastolic function, with reduced rate and extent of the rapid filling phase related to increased regional diastolic asynchrony.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of histamine on coronary hemodynamics in humans: role of H1 and H2 receptors.

To evaluate whether histamine exerts a direct effect on coronary hemodynamics in humans, and to investigate the role played by H1 and H2 receptors in this response, intracoronary saline solution or histamine (4 micrograms) was administered in 10 patients with normal coronary arteries during diagnostic cardiac catheterization. Histamine injection was repeated after intravenous cimetidine (400 mg) and diphenhydramine (10 mg). The electrocardiogram, arterial pressure and thermodilution coronary blood flow were continuously monitored during and for 40 seconds after each injection. Immediately after histamine injection there was a significant increase in coronary blood flow (65 +/- 6%) and a decrease in coronary vascular resistance (-40 +/- 3%) (both p less than 0.001), with minor changes in the RR interval and the mean arterial pressure. H2 receptor blockade with cimetidine did not affect these changes, while H1 receptor blockade with diphenhydramine significantly reduced the histamine-induced increase in coronary blood flow and the decrease in coronary vascular resistance (26 +/- 6%, p less than 0.005 and -18 +/- 5%, p less than 0.001, respectively). Twenty to 30 seconds after histamine injection, a significant decrease in mean arterial pressure (-17 +/- 2%, p less than 0.001) and in the RR interval (-4 +/- 1%, p less than 0.01) was observed. These changes persisted after H2 receptor blockade with cimetidine, but were completely abolished after H1 receptor blockade with diphenhydramine. In each case coronary and systemic hemodynamics returned to normal within 40 seconds of the injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional left ventricular asynchrony and impaired global left ventricular filling in hypertrophic cardiomyopathy: effect of verapamil.

Left ventricular relaxation and filling are impaired in many patients with hypertrophic cardiomyopathy. To investigate the influence of regional heterogeneity on these global abnormalities, 48 patients with hypertrophic cardiomyopathy and sinus rhythm were studied by radionuclide angiography before and after 1 to 2 weeks of verapamil therapy (320 to 640 mg/day, median 480). Left ventricular regional function was assessed by subdividing the ventricular region of interest into 20 sectors and into four quadrants from which regional time-activity curves were derived. Diastolic asynchrony was measured as the regional variation in timing between minimal volume and peak filling rate, and heterogeneity in the magnitude of rapid diastolic filling was measured as the regional variation in percent contribution of atrial systole to end-diastolic volume. Compared with 28 normal subjects, the patients with hypertrophic cardiomyopathy had greater regional variation in both timing (35 +/- 24 versus 12 +/- 6 ms, p less than 0.001) and magnitude (10 +/- 6 versus 7 +/- 4%, p less than 0.02) of rapid filling. Verapamil reduced the regional variation in timing (to 21 +/- 16 ms, p less than 0.001) and magnitude (to 7 +/- 3%, p less than 0.001) of rapid filling. These regional changes, indicating more uniform regional diastolic performance after verapamil, were associated with improved global diastolic filling: global rapid filling increased in both rate and magnitude and time to peak filling rate decreased. These findings indicate that the beneficial effect of verapamil on left ventricular diastolic function in hypertrophic cardiomyopathy may be mediated by reduction in regional asynchrony.

Pretreatment with verapamil in patients with persistent or chronic atrial fibrillation who underwent electrical cardioversion.

OBJECTIVES: To evaluate, in a prospective and randomized fashion, the efficacy of a pretreatment with verapamil (V) in reducing recurrences of atrial fibrillation (AF) after electrical cardioversion (C). BACKGROUND: The increased vulnerability for AF recurrence is probably due to AF-induced changes in the electrophysiologic properties of the atria. This electrical remodeling seems to be due to intracellular calcium overload. METHODS: One hundred seven patients with persistent or chronic AF underwent external and/or internal C. All patients received oral propafenone (P) (900 mg/day) three days before and during the entire period of follow-up (three months). In the first group, patients received only the P. In the second group, in adjunct to P, oral V (240 mg/day) was initiated three days before C and continued during the follow-up. Finally, in the third group, oral V was administered three days before and continued only for three days after electrical C. RESULTS: During the three months of follow-up, 23 patients (23.7%) had AF recurrence. Mantel-Haenszel cumulative chi-square reached a significant level only when comparing AF free survival curves of group I versus group II and group III (chi-square = 5.2 and 4, respectively; p < 0.05). Significantly, 15 (65.2%) AF relapses occurred during the first week after cardioversion with a higher incidence in group I (10/33 patients, 30.3%) than group II (2/34 patients, 5.9%; p = 0.01) and group III (3/30 patients, 10%; p = 0.04). CONCLUSIONS: Six days of oral V administration centered on the C day, combined with P, significantly reduce the incidence of early recurrences of AF compared with P alone.

Response to flecainide infusion predicts long-term success of hybrid pharmacologic and ablation therapy in patients with atrial fibrillation.

OBJECTIVES: We tested the hypothesis that the response to flecainide infusion can identify patients with atrial fibrillation (AF) in whom the hybrid pharmacologic and ablation therapy reduces the recurrences of AF. BACKGROUND: Infusion of class IC anti-arrhythmic drugs may promote transformation of AF into atrial flutter. Catheter ablation of atrial flutter has been demonstrated to be highly effective in preventing recurrences of atrial flutter. METHODS: Seventy-one consecutive patients with paroxysmal or chronic AF, in whom flecainide infusion (2 mg/kg body weight, intravenously) determined the transformation of AF into common atrial flutter (positive response), were randomized to receive one of the following treatments: oral pharmacologic treatment with flecainide (group A, n = 23); the hybrid treatment (catheter ablation of the inferior vena cava-tricuspid annulus isthmus, plus oral flecainide) (group B, n = 24); or catheter ablation of the isthmus only (group C, n = 24). Thirty-seven patients with a negative response to flecainide, who chose to be submitted to the hybrid treatment, were selected as the control group (group D). RESULTS: During a mean follow-up period of 24 +/- 7.2 months, the recurrences of AF and atrial flutter in group B (42%) were significantly lower than those in group A (78%, p < 0.001), group C (92%, p < 0.001) and group D (92%, p < 0.001). CONCLUSIONS: The creation of a complete bi-directional conduction block at the inferior vena cava-tricuspid annulus isthmus, plus flecainide administration, reduces the recurrences of both AF and atrial flutter in patients with class IC atrial flutter. Moreover, the early response to flecainide is safe and reliable in identifying patients who may benefit from this therapy.

Upper gastrointestinal symptoms and therapies in elderly out-patients, users of non-selective NSAIDs or coxibs.

BACKGROUND: The association between coxib or non-steroidal anti-inflammatory drug use with gastrointestinal symptoms and drug prescriptions in ambulatory elderly patients is not well defined. AIM: To evaluate the association between non-steroidal anti-inflammatory drug NSAID and coxib use with gastrointestinal symptoms and therapies in elderly subjects managed by their general practitioner. MATERIALS: The study was carried out by 133 general practitioners in Italy. By using a structured interview, sex, age, physical function, current medications, new drug prescriptions and upper gastrointestinal symptoms were registered from all elderly subjects who were referred to their general practitioners during a 2-week period. The numbers of hospitalizations, gastrointestinal bleeding events and gastrointestinal diagnostic procedures occurring during the last 6-month period were recorded. RESULTS: Included in this study were 5515 elderly subjects. The overall prevalence of drug use was 92%. Musculo-skeletal drugs were taken by 15% of patients; NSAIDs were taken by 6%, and coxibs by 3% of patients. A significantly higher prevalence of upper gastrointestinal symptoms was observed in elderly NSAID users compared with coxib users and non-users of musculo-skeletal drugs (44% vs. 33% vs. 32% respectively, P = 0.001). The prescriptions of drugs for acid-related disorders were significantly higher in patients who were concomitantly taking NSAID rather than coxibs (13% vs. 6%, P < 0.01). The prescriptions of drugs for acid-related disorders were significantly associated with the presence of upper gastrointestinal symptoms (OR = 1.7, 95% CI = 1.6-1.9), previous gastrointestinal disorders (OR = 1.1, 95% CI = 1.0-1.3) and NSAID use (OR = 1.5, 95% CI = 1.0-2.2), but no coxib use. CONCLUSION: In this elderly population, upper gastrointestinal symptoms and prescriptions for gastroenterological drugs were higher in non-steroidal anti-inflammatory drug users than coxib users and non-users of musculo-skeletal drugs.

Normalization of Functional Independence Measure variation improves assessment of stroke rehabilitation outcome.

BACKGROUND: Assessment of rehabilitation outcome is based on measuring the change in Functional Independence Measure (FIMTM) score between the start and end of rehabilitation. However, the raw FIMTM score gain is subject to a ceiling effect. Proposed solutions to this problem have incongruities that limit their use. AIM: The aim of this study was to determine the factors that influence functional outcome in stroke rehabilitation, exploring the possibility of developing an outcome index free of the ceiling effect and of the incongruities revealed by the proposed solutions. DESIGN: Retrospective study of the electronic clinical records of patients admitted to a rehabilitation unit over a period of 5 years. SETTING: Rehabilitation unit. POPULATION: A total of 224 patients admitted for first post-stroke rehabilitation of either ischaemic or hemorrhagic etiology. METHODS: Rehabilitation outcome was evaluated based on changes in both raw and "normalized" FIMTM motor and cognitive scores observed between hospital admission and discharge. Normalized differences are in the range 0-1 and may be considered an estimate of the actually attained fraction of the maximum expected recovery, while the modified algebraic formula (+1 to both numerator and denominator) is intended to correct the incongruities observed in available solutions. Seventeen prognostic factors were selected as possible effect modifiers of the outcome. A multivariable model-building strategy, based on fractional polynomials, was adopted to select the significant factors, and the stability of the results. RESULTS: The procedure adopted to normalize both FIMTM outcomes resolves the ceiling effect and corrects the incongruities noted with available solutions. The level of disability at admission is confirmed as the strongest prognostic factor associated with both cognitive and motor outcomes. The onset-admission interval negatively influence motor recovery, bat not cognitive one. CONCLUSION: There is strong evidence to support the proposal that it is advantageous to measure functional recovery by means of the normalized change in FIMTM score. Following a rehabilitation programme, functional recovery should be evaluated separately for motor and cognitive domains. Rehabilitation program should begin as soon as possible. CLINICAL REHABILITATION IMPACT: Improved assessment of rehabilitation outcome leads to increased achievement of a favourable treatment outcome.

Comparison of the safety and efficacy of delapril with enalapril in patients with congestive heart failure.

To evaluate the safety and efficacy of delapril versus enalapril in patients with congestive heart failure (CHF), New York Heart Association (NYHA) class II and III, 198 patients were enrolled in a study in 13 centers involving a double-blind parallel group design. After completing a 2-week run-in period on placebo, patients were randomized to receive delapril 7.5 mg twice daily or enalapril 2.5 mg twice daily for 2 weeks. The dose was then doubled for the remaining 6 weeks. In this phase, 1 patient in each group experienced orthostatic hypotension; the dose was then reduced to the initial dose for study completion. A total of 195 patients received active treatment (96 delapril, 99 enalapril). After 8 weeks' treatment, bicycle ergometry demonstrated a significant increase in exercise duration (p < 0.01) and workload (p < 0.01). Echo Doppler investigations showed a significant reduction (p < 0.01) in left ventricular end-systolic volume associated with a significant increase (p < 0.01) in ejection fraction and cardiac output. No clinically significant changes in blood pressure, heart rate, electrocardiogram, or biochemical and hematologic tests were found. There were no significant differences between treatment groups. Three patients in each group experienced adverse reactions requiring withdrawal of 1 patient in each group. Delapril 15 mg twice daily, like enalapril 5 mg twice daily, was effective in improving signs and symptoms of CHF and was well tolerated.

Assessment of regional left ventricular function by sector analysis: a method for objective evaluation of radionuclide blood pool studies.

Regional wall motion abnormalities are most often detected visually, and hence subjectively, in gated blood pool studies of the heart. Therefore, an automated method was developed to objectively assess regional left ventricular (LV) function. The method was tested in 26 normal volunteers and 29 patients with angiographically proved coronary artery disease. Fifteen patients with coronary artery disease had a normal LV ejection fraction (EF) at rest, and all had an abnormal EF response with exercise; 23 had visual regional wall motion abnormalities with rest or exercise. The left ventricle was divided into 28 sectors that radiated from the LV center of gravity, with 1 region at the LV center. A time-activity curve was generated for each sector and the EF and Fourier phase were computed from each curve. Rest and exercise sector EF versus sector number plots were superimposed and the area difference between these 2 curves was taken as an index of regional contraction. Similarly, an estimator of sector phase differences, obtained from the plot of phase versus sector number, was taken as an index of wall motion asynchrony. Analysis of the reliability of these 2 indexes suggests that this automated technique has at least the same efficiency as subjective evaluation of gated blood pool studies, but possesses the advantage of objectivity. The technique may also be useful in localizing regional defects and, perhaps, in detecting mild abnormalities not readily perceived visually.

The effect of coronary artery bypass grafting on left ventricular systolic function at rest: evidence for preoperative subclinical myocardial ischemia.

Successful coronary artery bypass grafting (CABG) improves exercise-induced left ventricular (LV) dysfunction in patients with coronary artery disease (CAD), but its potential for improving resting LV function remains controversial. To assess the influence of CABG on LV function at rest, 31 CAD patients without previous myocardial infarction were studied before and 6 months after CABG by radionuclide angiography after all cardiac medicines were withdrawn. No patient had angina or ischemic electrocardiographic changes at rest. In 27 patients with patent bypass grafts, CABG significantly increased LV ejection fraction during exercise (47 +/- 11% before to 63 +/- 9% after operation, p less than 0.001), indicating reduction in exercise-induced LV ischemia. Moreover, LV ejection fraction at rest also increased (55 +/- 9 to 60 +/- 8%, p less than 0.001), with 20 of 27 patients manifesting an increase compared with preoperative values. Eleven of these 20 patients had apparently normal LV function at rest (ejection fraction and regional wall motion) before CABG. LV regional ejection fraction was computed by dividing the LV region of interest into 20 sectors. Regional analysis indicated that improved ejection fraction at rest after CABG occurred in regions developing ischemia during exercise before CABG. In 4 patients with occluded grafts, the ejection fraction at rest was unchanged by CABG globally (59 +/- 8 to 58 +/- 9%, difference not significant) and regionally. Thus, LV global and regional function at rest improved after successful CABG, even in patients with normal global LV ejection fraction and no visually detectable wall motion abnormality before surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Portal vein pulsatility ratio provides a measure of right heart function in chronic heart failure.

Portal vein flow was recorded by color Doppler sonography in 31 patients with chronic heart failure and 18 control subjects. Compared with patients showing a forward flow (Group A), those with reversed portal vein flow (Group B) had higher prevalence of tricuspid regurgitation (75% vs. 43%), hepatic congestion (100% vs. 30%) and ascites (50% vs. 18%), and showed higher right atrial pressure (25.3 +/- 3.01 mmHg vs. 11.8 +/- 5.75 mmHg, p < 0.01). In controls, portal vein pulsatility ratio was 0.66 +/- 0.08, in Group A it was 0.46 +/- 0.28 (p < 0.01), in Group B -0.60 +/- 0.19 (p < 0.01). Portal vein pulsatility ratio negatively correlated with right atrial pressure (r = -0.87; p < 0.01). In Group A, hepatic congestion, ascites and tricuspid regurgitation were associated with a higher portal vein pulsatility. This study indicates that portal vein pulsatility ratio reflects the level of impairment of the right heart.

Congestive heart failure in the elderly.

Several aspects of congestive heart failure are discussed in the light of international literature and of recent findings of our group. The annual incidence of heart failure in elderly subjects, aged >or=75y, is 13 to 50/1000, while it is 1.6/1000 in people aged 45-54 y. The prevalence of heart failure is about 3% in subjects aged 45-64% in subjects aged more than 65 y and 10% in subjects aged more than 75 y. These data are confirmed by our population based study in elderly subjects. The etiology of congestive heart failure is similar in elderly and middle-aged patients. However, several anatomo-functional, hormonal and autonomic nervous system changes, typical of congestive heart failure, occur during physiologic ageing processes also. These findings may explain the dramatic evolution of congestive heart failure in elderly patients. Moreover, some features of the elderly - e.g. comorbidity, atypical clinical presentations, loss of autonomy, increased iatrogen risk should be considered. No specific drugs exist for the pharmacologic treatment of heart failure in the elderly, so that the geriatric specificity in the treatment of heart failure can be recognized in the art of drug choice and dosage, to obtain the best results with the least side effects. The multiple etiology of congestive heart failure, the comorbidity, the loss of autonomy and the deterioration of cognitive functions suggest the need for multidimensional approach and continuative intervention in elderly patients with heart disease, and in particular with congestive heart failure. Further studies on disease- and age-related changes are necessary to develop new and more potent strategies to secure 'successful ageing'.

Clinical determinants of long-term mortality in elderly patients with heart disease.

To determine which of the many clinical parameters routinely collected influence mortality in patients with low left ventricular ejection fraction (LVEF) (< 45% at radionuclide ventriculography), 128 elderly patients (mean age 79 +/- 3 years) with various heart diseases were prospectively followed for 3 years. Twenty-eight-percent had coronary heart disease, 16% hypertensive heart disease, 7% valvular heart disease. The remaining 62 patients (48%) made up a group comprising patients with primitive cardiomyopathy, cor pulmonary with no evidence of coronary heart disease, valvular disease or hypertensive heart disease. Thirty-four-percent of all patients were classified as having congestive heart failure (CHF). Age, sex and 37 clinical variables were analyzed using a Cox proportional model. Forty-four patients died, 36 (82%) of sudden cardiac death. Ten characteristics at study entry predicted an increased mortality risk: S3 gallop, number of clinical signs >or= 3, LVEF or= III, dyspnea, digoxin treatment, rales, number of symptoms >or= 4, asthenia, associated pulmonary disease. Long-term survival of very elderly patients with low ejection fraction is related to the functional capacity, the severity of symptoms and the number of clinical signs. Moreover a LVEF

Quantification of pilomotor nerves: a new tool to evaluate autonomic involvement in diabetes.

OBJECTIVES: Quantification of the complex, autonomic networks in the skin is difficult. Although sporadic attempts focusing mainly on sudomotor plexus have been reported, an easy and reliable method of quantification has not yet been made available. We developed a method to quantify pilomotor nerve fibers (PNFs), which, compared to sudomotor nerves, have a less complex pattern. We used this procedure on a population of normal and diabetic subjects, and propose it as a new tool to study cutaneous autonomic nerves. METHODS: Skin biopsies were performed from thigh and distal leg in 20 diabetic patients and 20 age- and sex-matched controls. Samples were processed applying indirect immunofluorescence and using pan-neuronal and selective markers for cholinergic and noradrenergic fibers. Pilomotor nerve fiber density was blindly calculated on single 2-µm optical sections selected from confocal z-stacks. Interobserver and intraobserver reliability was evaluated. Results were compared with values obtained by 2 other methods that explored PNFs more extensively. Pilomotor nerve fibers density was compared to epidermal nerve fiber (ENF) density, to pilocarpine-activated sweat gland density, and to the severity of neuropathy as assessed by the modified total neuropathy score. RESULTS: A significant loss of PNFs was found in diabetic subjects' thigh and leg. PNFs density did not correlate with ENF density, disease duration, or total neuropathy score. Noradrenergic PNFs correlated instead with sweating impairment. CONCLUSIONS: A reliable assessment of PNF density is possible. When studying cutaneous innervation, PNF quantification should be done to gain information on autonomic nerves in addition to somatic nerves.

Influence of comorbidity and cognitive status on instrumental activities of daily living in amnestic mild cognitive impairment: results from the ReGAl project.

OBJECTIVES: To investigate whether amnestic mild cognitive impairment (aMCI) is characterised by restriction in instrumental activities of daily living (IADL). Further, to examine the role of comorbidity and cognitive performance on IADL changes in aMCI subjects. METHODS: The study included 132 subjects with aMCI and 249 subjects with no cognitive impairment (NCI), consecutively enrolled as outpatients in a multicentric Italian clinical-based study, the ReGAl Project. All subjects underwent a comprehensive evaluation including clinical examination, laboratory screening, neuroimaging and cognitive and behavioral assessments. Functional status was evaluated by the Lawton's Instrumental Activities of Daily Living (IADL) scale. Comorbidity was evaluated by the Cumulative Illness Rating Scale (CIRS). Cognitive evaluation included tests assessing episodic memory, language, attention/executive functioning and praxis, as well as the the Mini-Mental State Examination (MMSE) as a measure of global cognition. RESULTS: Subjects with aMCI had higher IADL changes than NCI. Among IADL items, aMCI subjects showed a significant impairment in shopping, taking drugs, and handling economy; however also NCI had minor IADL changes regarding cooking, washing and cleaning. IADL restriction in aMCI subjects was significantly associated with cognitive performance, mainly related to executive functioning, but not with comorbidity. On the contrary, in NCI sensory impairment accounts for slight IADL changes. CONCLUSION: In aMCI subjects a mild degree of cognitive deterioration has a stronger impact on IADL than somatic comorbidity. Current diagnostic criteria for MCI should include a mild impairment in IADL.