Riccardo Livi

A neural network expert system for diagnosing and treating hypertension

Hypernet (Hypertension Neural Expert Therapist), a neural network expert system for diagnosing and treating hypertension, is described. After a brief look at artificial neural networks, the authors describe the structure of the three modules that make up Hypernet, starting with the specific problem each network is intended to solve and explaining how the network is expected to operate. The tools developed for implementing the system are a compiler for a simple descriptive language that enables the authors to define, train, and test networks; a graphic editor that translates the network drawn by the user into the proper statements; and a set of programs for interactively generating the examples. The data used as examples, the learning phase, and the results of tests for evaluating the performance of each network are described. and conclusions about overall system results are presented.<<ETX>>

Systemic amyloidosis: a challenge for the rheumatologist

Amyloidosis comprises a group of diseases characterized by the extracellular deposition of insoluble fibrillar proteins. This mechanism generates different clinical syndromes depending on the site and extent of organ involvement. Amyloidosis is classified into categories of systemic and localized disease. Systemic amyloidosis is further subdivided into a hereditary familial form (for example, ATTR amyloidosis), a reactive form (AA amyloidosis), dialysis-related (Aβ2M) amyloidosis and immunoglobulin light chain (AL) amyloidosis. Treatment can be symptomatic, directed at the affected organ, or can be directed at reducing the production of the abnormal proteins with different strategies. Despite advances in treatment, the prognosis is still poor and depends on the underlying disease as well as the type and degree of dysfunction in involved organs. Early diagnosis is essential because patients with advanced disease are generally unable to undergo intensive therapy. Patients with systemic amyloidosis often present to a rheumatologist not only because the disease can include musculoskeletal and articular symptoms but also because it can be associated with chronic rheumatic diseases. This Review discusses the clinical features of amyloidosis and its rheumatic manifestations. The various types of amyloidosis, as well their prognosis and treatment, are also presented.

Exercise Doppler Echocardiography Identifies Preclinic Asymptomatic Pulmonary Hypertension in Systemic Sclerosis

Abstract:  In systemic sclerosis (SSc), the involvement of the interstitium or vascular system of the lung may lead to pulmonary arterial hypertension (PAH). PAH is often asymptomatic or oligosymptomatic in early SSc and, when it becomes symptomatic, pulmonary vascular system is already damaged. Exercise echocardiography (ex‐echo), measuring pulmonary artery pressure (PAP) during exercise and allowing to differentiate physiologic from altered PAP responses, may identify subclinical PAH. Our aims were (a) to evaluate by ex‐echo the change of PAP in patients with SSc without lung involvement; and (b) to correlate PAP during exercise (ex‐PAP) values to clinical and biohumoral parameters of PAH. Twenty‐seven patients with limited SSc (lSSc) without interstitial lung involvement were studied. Patients underwent rest and exercise two‐dimensional and Doppler echocardiography by supine cycloergometer. Systolic PAP was calculated using the maximum systolic velocity of the tricuspid regurgitant jet at rest and during exercise values of systolic PAP exceeding 40 mmHg at ex‐echo were considered as abnormal, and biohumoral markers potentially related to PAH were assessed. Eighteen of 27 SSc patients presented an ex‐PAP >40 mmHg, while in 9 of 27 patients ex‐PAP values remained <40 mmHg (48.8 ± 4.5 mmHg versus 36.2 ± 3.1 mmHg; P < 0.001). Other echocardiographic and ergometric parameters, clinical tests, and biohumoral markers were not different in the two groups. Ex‐PAP significantly correlated with D‐dimer (P= 0.0125; r2= 0.2029). Ex‐echo identifies a cluster of SSc patients with subclinical PAH that may develop PAH. This group should be followed up and may be considered for specific therapies to prevent disease evolution.

Melatonin is a safe and effective treatment for chronic pulmonary and extrapulmonary sarcoidosis

Abstract:   Chronic sarcoidosis (CS) is often unresponsive to usual treatments. Melatonin, an immunoregulatory drug, was employed in CS patients in whom usual treatments were ineffective or induced severe side effects. Melatonin was given for 2 yr (20 mg/day in the first year, 10 mg/day in the second year) to 18 CS patients. Pulmonary function tests, chest X rays, pulmonary computed tomography, Ga67 scintigraphy and angiotensin‐converting enzyme (ACE) were assayed at baseline and in the follow‐up. Normalization of ACE, improvement of pulmonary parameters and resolution of skin involvement were found in the patients given melatonin. After 24 months of melatonin therapy, hylar adenopathy completely resolved in eight patients and parenchymal lesions were markedly improved in all patients; in the five patients with reduced diffusion capacity of the lung for carbon monoxide, the values normalized after 6 months of therapy and remained stable until month 24. After 24 months, Ga67 pulmonary and extra‐pulmonary uptake was totally normalized in seven patients and, at month 12 months, ACE was normalized in six patients in which the values were high at the baseline. Skin lesions, present in three patients, completely disappeared at month 24 months. No side effects were experienced and no disease relapse was observed during melatonin treatment. Melatonin may be an effective and safe therapy for CS when other treatments fail or cause side effects.

Reduced circulating levels of angiotensin-(1–7) in systemic sclerosis: a new pathway in the dysregulation of endothelial-dependent vascular tone control

Objective: Systemic sclerosis (SSc) impairs endothelium-dependent vasodilatation. Among angiotensin I (Ang I)-derived compounds, vasoconstrictor angiotensin II (Ang II) and vasodilator angiotensin-(1–7) (Ang-(1–7)), cleaved from ACE and neutral endopeptidase (NEP) 24.11, respectively, play an important role in vascular tone regulation. Ang-(1–7) may act independently or by activating other vasodilating molecules, such as nitric oxide (NO) or prostaglandin I2 (PGI2). Our aim was to assess, in patients with SSc, circulating levels of Ang I, Ang II and Ang-(1–7), with their metabolising enzymes ACE and NEP, and levels of NO and PGI2, and to correlate them to the main characteristics of SSc. Methods: Levels of Ang I, Ang II, Ang-(1–7), NEP, ACE, NO and PGI2 were measured in 32 patients with SSc, who were also assessed for humoral and clinical characteristics, and 55 controls. Results: Plasma Ang I, Ang II and Ang-(1–7) levels were lower in patients with SSc than in controls (p<0.001in all cases). When Ang II and Ang-(1–7) levels were expressed as a function of the available Ang I, lower Ang-(1–7) levels in patients with SSc than in controls were confirmed (p<0.001), while no difference was found for Ang II levels. In patients with SSc, the Ang II/Ang-(1–7) ratio indicated a prevalence of Ang II over Ang-(1–7), while in controls Ang-(1–7) was prevalent (p<0.001). Levels of ACE, NEP, NO and PGI2 were lower in patients with SSc than in controls (p<0.05 in all cases). Conclusion: In patients with SSc, prevalence of the vasoconstricting Ang II over the vasodilator Ang-(1–7) suggests a dysfunction of the angiotensin-derived cascade that may contribute to dysregulation of vascular tone.

Lack of activation of renal functional reserve predicts the risk of significant renal involvement in systemic sclerosis

Objective To evaluate if defective activation of renal functional reserve (RFR) in systemic sclerosis (SSc) without clinical signs of renal involvement predicts the risk of developing clinically relevant renal damage. Methods Twenty-eight normotensive SSc patients with normal renal function and no urinary abnormalities were submitted to an intravenous amino acid load to activate RFR. Nineteen patients (six with diffuse cutaneous SSc (dcSSc)) had an RFR activation defect, while nine (two with dcSSc) showed normal RFR. All patients were followed up for 5 years, with periodic evaluation of renal function, urinary protein excretion and systemic blood pressure (BP). Results At admission, patients with normal RFR had lower BP than those with abnormal RFR; no age, disease duration or creatinine clearance (CCr) differences were found. Five years later, patients with abnormal RFR showed, with respect to basal values, a significantly higher CCr reduction than patients with normal RFR (mean percent decrease 15.4±9.5 vs 2.6±3.8, p<0.001). Among patients with abnormal RFR, 13 (68.4%) showed a CCr reduction of ≥2 ml/min/year, with a final CCr of ≤70 ml/min in eight cases; two patients developed microalbuminuria and 10 grade 1 or 2 systemic hypertension. Significant CCr reduction rates were found in eight patients with high BP and in five patients who remained normotensive. No patient with normal RFR had proteinuria or high BP during follow-up. Conclusions Lack of RFR activation is an early sign of renal involvement in SSc, and is a harbinger of an increased risk of developing renal insufficiency and systemic hypertension.

Simultaneous and sequential same-arm measurements in the validation studies of automated blood pressure measuring devices

The oscillometric ambulatory blood pressure recorder Daypress 500 was validated according to the British Hypertension Society protocol. Both sequential and simultaneous measurements were used. Multiple regression analysis demonstrated a significant influence of subject pulse pressure and arm circumference on device-observer systolic pressure differences. Differences between observer consecutive readings were inversely related to heart rate. Device and observer blood pressure readings were closer at simultaneous than at sequential measurements. However, both kinds of measurement led to the same final evaluation (A for diastolic and B for systolic blood pressure), provided that the appropriate grading criteria were applied for each method.

Age effects upon the harmonic structure of human blood pressure in clinical health

Ambulatory blood pressure monitoring of 180 clinically healthy adults of both genders is used to investigate and compare ultradian aspects of systolic and diastolic blood pressure as a function of age. Three age categories are considered: 20-40, 40-60, and over 60 years of age. results from least-squares spectra of each data series are further examined by analysis of variance. Gender and age effects are found to characterize the waveform of human blood pressure. These effects can be quantified by spectral analysis and may represent gauges of aging.<<ETX>>

Instrumentation for Human Blood Pressure Rhythm Assessment by Self-Measurement

Herein, we wish to document the need for instrumentation for autorhythmometry, notably of blood pressure (BP). Autorhythmometry has been introduced by us in schools, in the home and in the clinic. Despite obvious limitations of the existing instrumentation, the merits of autorhythmometry pertain to (early) diagnosis, (optimal) treatment and, first and foremost, to prevention, as illustrated by the following results.

Incidence and characteristics of asymptomatic distal deep vein thrombosis unexpectedly found at admission in an Internal Medicine setting.

INTRODUCTION Lower limb deep vein thrombosis (DVT) is the most frequent clinical manifestation of venous thromboembolism (VTE) and can involve proximal or distal veins. Distal DVT (dDVT) is often asymptomatic and data about its incidence and prognosis are scanty, especially in high risk medical inpatients. Therefore, no consensus exists on the value of detecting and treating dDVTs. Aim of study was to evaluate incidence and characteristics of asymptomatic isolated dDVT at admission in an Internal Medicine department. MATERIALS AND METHODS Consecutive patients hospitalized for acute medical illnesses, in whom VTE was not the admission diagnosis, underwent Doppler Ultrasonography. For all patients with dDVT standard treatment with therapeutic doses of low molecular weight heparin or fondaparinux was proposed. Follow-up visits were scheduled at 1, 6 and 12weeks. RESULTS One-hundred-fifty-four patients were enrolled. In 4.5% a proximal DVT and in 16.2% an asymptomatic dDVT were found. Female sex, elevated age and renal and electrolyte abnormalities were significantly associated to dDVT (p=0.014, p=0.009 and p=0.046, respectively). Only low degree of mobility (LDM) was independently associated to dDVT [OR 7.97 (95%CI 2.42-26.27), p=0.001)]. A high mortality rate, not for VTE-related causes, was found, especially in the first week, among dDVT patients. CONCLUSIONS We found a high incidence of clinically silent dDVTs. LDM evaluation could be useful to select patients at high risk in whom to perform a search for dDVT.