[Echocardiographic evaluation of coronary flow reserve in patients with essential hypertension]. / Studio ecocardiografico della riserva di flusso coronarico in pazienti con ipertensione arteriosa essenziale.

BACKGROUND: In patients with essential arterial hypertension (EAH) the left heart ventricular hypertrophy (LVH) causes structural and functional alterations of the coronary vessels that can alter the coronary blood flow reserve. The aim of this study is to evaluate in hypertensive patients with or without LVH versus normotensive subjects, the blood flow and the coronary vasodilatation capability and the coronary blood flow reserve in basal conditions and during dipiridamole i.v. infusion. METHODS: Eighty patients have been selected by ECG, echo color Doppler, transesophageal echocardiography: 50 were hypertensive patients with and without LVH, from mild to moderate to severe and 30 were normotensive subjects. The enrolled patients underwent a first transesophageal echocardiography, before and during infusion of 0.86 mg/kg of dipiridamole in growing doses, 0.56 in four minutes followed after three minutes by 0.30 mg/kg. The observation lasted 18 months, and no patients left the study. RESULTS: The coronary resistances in hypertensive patients were significintally reduced during dipiridamole infusion, maintaining their level higher compared to the normal controls. The reduced coronary vasodilatation capability in hypertensive subjects could be due to an increase of the basal vessel tone and/or a reduced compliance of the coronary resistances. The coronary blood flow reserve is significantly reduced in all hypertensive studied, included those without LVH. It is suggested that this is secondary to increase of the coronary blood flow and tone. CONCLUSIONS: In conclusion essential arterial hypertension is the cause of early anatomical and functional coronary alterations leading hypertensive subjects to risk for coronary events before LVH.

Bioavailability and antioxidant activity of some food supplements in men and women using the D-Roms test as a marker of oxidative stress.

Most antioxidants show contradictory behaviors because in the biological environment, for unpredictable reasons, they can become prooxidants. Recently, a new simple method to monitor oxidative stress in serum was developed. This test detects the derivatives of reactive oxygen metabolites (D-Roms). Hydroperoxides are converted into radicals that oxidize N,N-diethyl-para-phenylendiamine and that can be detected through spectrophotometric procedures as U.CARR. (Carratelli units). One U.CARR. corresponds to 0.8 mg/L hydrogen peroxide. In normal subjects U.CARR. values range from 250 to 300. Values outside this range indicate a modification of the prooxidant/antioxidant ratio. On the basis of this method, we tested three different formulas of antioxidants (F1, F2, F3) in 14 apparently healthy volunteers (11 men and 3 women). Formula 1 was composed of 5 mg zinc, 48 microg selenium, 400 microg vitamin A (as retinol acetate), 50 microg beta-carotene, 15 mg vitamin E (as dl-alpha-tocopheryl acetate) and 10 mg L-cysteine. Formula 2 was composed of 30 mg bioflavonoids from citrus, 30 mg vitamin C (as L-ascorbic acid), 10 mg coenzyme Q(10) and 1 mg vitamin B-6 (as pyridoxine hydrochloride). Formula 3 was composed of Formula 1 plus Formula 2. Each formula was prepared in dry capsules (formulation D1, D2, D3) or in a fluid form (formulation P1, P2, P3). Each formulation was administered for 1 wk in a crossover design. A 15% deviation of U.CARR. levels was chosen as the cut-off value for a significant change in oxidative stress. Formulas F1 and F3 reduced mean U.CARR. levels in most of the treated subjects (t test, P < 0.05), whereas F2 was not active. Fluid formulations were more active than dry formulations (chi(2) test, P < 0.05). In some cases, a slight increase in oxidative stress was detected. These minimal increases were not related to any particular antioxidant formula. In one subject only, the administration of the dry formulation (D1), increased oxidative stress to a level that reached the cut-off value. In conclusion, when antioxidants are taken in combination at low dosages they reduce oxidative stress, and little relevant prooxidant activity is detectable.

[Behaviour of free radicals in Alzheimer's disease]. / Comportamento dei radicali liberi nella malattia di Alzheimer.

BACKGROUND: The objective of this study is to evaluate the oxidative stress status in patients affected by Alzheimer's disease, considering the role played by the free radicals in the progression and determination of this disease. METHODS: We have studied 13 patients aged between 65 and 84 years and diagnosed with Alzheimer's disease on the basis of Brain CT scan or MRI results, PTEA (uditive mapped slow potential waves), EEG analysis, evaluation questionnaire (MMSE, ADAS), free radicals levels. RESULTS: This study proved the presence of an oxidative stress status in all patients studied, showing an interaction between the disease and oxidative status. A reduction of the free radicals levels after therapy with determinable anti radicals has also been observed. CONCLUSIONS: The existence between Alzheimer's disease and oxidative stress has already been demonstrated. This study is a contribution to this orientation. Further studies are suggested on the preventive effects, but particularly to demonstrate if the use of antioxidants may be able to decrease or stop the evolution of this disease.

[Treatment of chronic arterial occlusive disease of the lower limbs with propionyl-1-carnitine in elderly patients]. / Trattamento con L-propionilcarnitina dell'arteriopatia obliterante degli arti inferiori in pazienti anziani.

BACKGROUND: Atherosclerosis is the most common pathology affecting the arterial system in elderly patients and arterial occlusive disease of the lower limbs represents one of the most severe complications. Intermittent claudication is the clinical expression of the ischemia underlying this arterial disease. Patients suffering from this complication present altered homeostasis of carnitine that results, by means of various mechanisms, in an alteration of the oxidative processes and damages the oxidative phosphorylation of the skeletal muscle. The effects of treatment with propionyl-l-carnitine (PLC) in a group of elderly patients with intermittent claudication (IC) are studied. METHODS: 39 elderly patients with IC were enrolled in an open study. The diagnosis was made using arterial colour ultrasonography of the lower limbs and patients were asked to perform the treadmill test. All patients received 300 mg i.v. PLC a day for 2 weeks and 1 g twice a day per os for 18 weeks. Patients presenting heart, respiratory or other problems restricting physical exercise were excluded from the study. RESULTS: After 5 months of treatment an improvement was obtained in the distance after which IC appeared (from 213+/-8 m to 357+/-13 m) and the maximum distance covered (from 307+/-12 m to 549+/-23 m). CONCLUSIONS: The results of this study allowed us to evaluate the efficacy of this drug on the severely disabling pain affecting the quality of life of patients, thus enabling the maximum distance covered by these patients to be increased. Moreover, the drug was well tolerated (only two patients reported slight collateral effects ascribed to the drug) and safe to use. It represents a valid conservative, non-surgical treatment which can be administered to all patients with intermittent claudication.

Treatment of arterial hypertension in the elderly with diltiazem vs ramipril.

BACKGROUND: Around 40% of the elderly population suffer from arterial hypertension. An effective antihypertensive treatment is therefore required. Calcium antagonists are used to treat hypertension because, owing to their mechanism of action, they can provoke systemic, as well as coronary vasodilatation. In this study the authors aimed to evaluate the activity and tolerability of diltiazem compared to ramipril in a group of elderly patients suffering from essential arterial hypertension. METHODS: A controlled single-blind study was performed in which patients were randomly assigned to one of two groups, A and B, consisting of 25 patients each, treated respectively with 300 mg sustained-release diltiazem or 5 mg ramipril in a single daily dose. The study lasted 6 months and evaluated systolic and diastolic pressure and heart rate. RESULTS: The evolution was positive in all patients in Group A and most patients in Group B, with the normalisation of both systolic and diastolic values. Heart rate showed a more persistent fall in Group A, but this was expected owing to the mechanism of action of diltiazem. No patient in Group A had to suspend treatment, whereas one patient in Group B had to interrupt therapy following the onset of a persistent cough. CONCLUSIONS: Both treatments resulted in similar changes in systolic and diastolic arterial blood pressure. In the light of these results, it can be affirmed that, at an oral dose of 300 mg/day, sustained-release diltiazem was found to be effective and well tolerated in the treatment of mild to moderate essential arterial hypertension in the aged.

Altered retinoic acid sensitivity and temporal expression of Hox genes in polycomb-M33-deficient mice.

The Polycomb group genes are required for the correct expression of the homeotic complex genes and segment specification during Drosophila embryogenesis and larval development. In mouse, inactivation studies of several Polycomb group genes indicate that they are also involved in Hox gene regulation. We have used our previously generated M33 mutants to study the function of M33, the mouse homologue of the Polycomb gene of Drosophila. In this paper, we show that in the absence of M33, the window of Hoxd4 retinoic acid (RA) responsiveness is opened earlier and that Hoxd11 gene expression is activated earlier in development This indicates that M33 antagonizes the RA pathway and has a function in the establishment of the early temporal sequence of activation of Hox genes. Despite the early activation, A-P boundaries are correct in later stages, indicating a separate control mechanism for early aspects of Hox regulation. This raises a number of interesting issues with respect to the roles of both Pc-G proteins and Hox regulatory mechanisms. We propose that a function of the M33 protein is to control the accessibility of retinoic acid response elements in the vicinity of Hox genes regulatory regions by direct or indirect mechanisms or both. This could provide a means for preventing ectopic transactivation early in development and be part of the molecular basis for temporal colinearity of Hox gene expression.

Helicobacter pylori eradication in elderly patients.

BACKGROUND: The elderly population is rising constantly in industrialised countries. Accord-ing to ISTAT, within the next 15 years the number of over-80-year-olds in Italy will top 2.6 million. In the elderly, the incidence of peptic ulcer tends to increase with age. An important etiological role has recently been attributed to helicobacter pylori (HP) which has been identified as a risk factor for the various forms of gastric cancer. METHODS: The study was carried out in 57 patients (45 with HP+ duodenal ulcer and 12 with HP+ gastric ulcer). Diagnosis was made on the basis of endoscopic tests, histological tests and urea breath test. Patients were treated orally with clarithromycin 500 mg twice a day for 14 days), amoxycillin (1 g twice a day for 14 days) and omeprazole (20 mg once a day for 30 days). RESULTS: The results showed an eradication of HP in 89% of duodenal ulcer patients and 83.3% of peptic ulcer patients. CONCLUSIONS: The treatment protocol used in this study achieved percentages of eradication that are comparable to those reported by other authors using different protocols; the percentages were sufficiently high for the protocol to be regarded as efficacious and well tolerated by patients. In fact, the scarce incidence of undesirable effects and excellent patient compliance are of particular interest in view of the fact that elderly patients have a higher risk of side-effects.

[Treatment of postmenopausal osteoporosis with etidronate]. / Trattamento dell'osteoporosi post-menopausale con etidronato.

BACKGROUND: Osteoporosis is a widespread social disease as it is considered to be the most common pathology affecting bone metabolism in the elderly. A group of patients suffering from post-menopausal osteoporosis have been treated with etidronate. METHODS: This controlled study was performed on 32 post-menopausal women aged between 53 and 66 suffering from post-menopausal osteoporosis, treated at the Department of Geriatrics of the University of Catania where patients mainly come from Sicily and Southern Italy. The diagnosis was made after clinical examination and humoral tests as well as computerised total body bone densitometry. Patients were treated according to an intermittent cyclic scheme which consisted in the administration of 400 mg etidronate per day for 14 days and 500 mg calcium carbonate per day for the following 76 days. This treatment had to be repeated for one year. Patients in the placebo group were not treated. RESULTS: The results of the study showed a significant increase of total body bone mineral density +5.6% (p = 0.009), with a considerable improvement of clinical symptoms. No significant variation was detected in the control group. CONCLUSIONS: On the basis of the results obtained, the conclusion is drawn that the intermittent cyclic treatment with etidronate is effective, well tolerated and with good compliance. Moreover, this drug proved to have no side effects.

A simple test to monitor oxidative stress.

BACKGROUND: The role of oxygen free radicals is considered important in the development of cardiovascular disease. However, until recently determination of free radicals plasma levels and the effect of antioxidant therapy on these levels has been difficult. The aim of the study was to determine the oxidative stress and the effect of the antioxidant compound AR(D) Stenovit on this stress in normal subjects and patients with intermittent claudication after oral administration for one week. METHODS: A portable, free radicals (FRs) determination system (D-Roms test, Diacron, Grosseto, Italy) was used. This test is based on the ability of transition metals to catalyse in the presence of peroxides with formation of FRs which are trapped by an alchilamine. The alchilamine reacts forming a coloured radical detectable at 505 nm. The reagents utilised are the cromogen (R1, an alchilamine) and a pH 4.8 buffer (R2). Ten microl of hemolysis-free serum are to 1 ml of R2 and to 10 microl of R1. The sample is mixed, incubated (1 min; 37 degrees C) and read for optical density. After another minute, the sample is read again. The average delta A/min is multiplied by a K factor and calculated using serum with defined value. RESULTS: In normal subjects the mean (+/-SD) levels of free radicals were 312+/-49 U.CARR (Carratelli units) before treatment and 218+/-33 U.CARR after treatment (p<0.05). A decrease of at least 10% was detected in every subject. In patients with peripheral vascular disease the mean (+/-SD) levels of free radicals were 404+/-42 U.CARR before treatment and 278+/-33 U.CARR after treatment (p<0.02). A decrease of at least 15% was detected in every patient (medium value 31%). CONCLUSIONS: The D-Roms test provides a simple, inexpensive and practical method to identify subjects with a high level of oxidative stress and to demonstrate the effect of treatment. The compound AR(D) Stenovit is effective in reducing circulating free radicals. Its action on the progression of atherosclerotic disease should be assessed in future studies.

Helicobacter pylori-positive functional dyspepsia in elderly patients: comparison of two treatments.

The association of Helicobacter pylori and functional dyspepsia is not well defined. The role of H. pylori on dyspeptic symptoms is still controversial. The aim of this study is to confirm the efficacy of H. pylori eradication by two different commonly used treatment regimens, as well as to examine the improvement of the dyspeptic symptoms by eradicating H. pylori. H. pylori functional dyspepsia is prevalent in people over 60 years old. In this age group we treated 126 patients with bismuth plus metronidazole and amoxicillin (group A, 67 patients) versus omeprazole plus amoxicillin (group B, 59 patients). Results were statistically analyzed utilizing the Wilcoxon signed-rank test, McNemer test and chi-square test; P < 0.05 was considered significant. Two months after the end of therapy we observed an eradication rate of 66.1% in group A vs 64.3% in group B. All treated patients showed improvement in symptomatology. Although there was no significant difference between patients in whom H. pylori was or was not eradicated within the respective groups, when examining all H. pylori-positive patients versus H. pylori-negative posttreatment patients, there was a significant reduction (P < 0.05) in all four symptoms of functional dyspepsia measured. In conclusion, we suggest that patients treated with H. pylori-eradicating therapeutic regimens have an improvement in functional dyspepsia symptoms. We shall prefer the dual therapy as compared to the triple therapy. We believe that eradicating treatment to eradicate H. pylori in the elderly patients with H. pylori-related functional dyspepsia will reduce health care costs by reducing the number of subsequent visits.

Different types of interferon for the therapy of HCV chronic active hepatitis in the elderly patient.

HCV correlated hepatitis is a pathology on the increase, and it is especially affecting patients above 60 years old. The only treatment for this disease is therapy with different types of interferon. The authors take into examination three of their previous studies on treatment of HCV correlated chronic hepatitis in the elderly using different types of interferon: recombinant interferon alpha, interferon beta, and lymphoblastoid interferon, in order to evaluate which one, among the three, should be the best for the treatment of this pathology in the elderly. The data show that recombinant interferon alpha is preferable since the remission percentage is higher (75%), compared to beta (53.8%) and lymphoblastoid interferon (60%). As far as the relevant side-effects in elderly patients are concerned, beta-interferon therapy is almost with no side-effects. Even in cases where there could be a possible higher exposure to side-effects linked to the use of recombinant interferon alpha, still, the risk/benefit ratio suggests that this particular drug should be used for treating this pathology in elderly patients.

[Spectral analysis of EEG signals in Alzheimer's disease]. / Analisi spettrale dei segnali EEG nella malattia di Alzheimer.

UNLABELLED: Alzheimer's disease (AD) represents the most frequent cause of senile dementia in Western countries. The disease has a slow onset and gradual progress. Over the past few years considerable importance has been attributed to the diagnostic techniques of brain imaging able to highlight morphological and functional images. EEG mapping is one of the most widely used methods. METHODS: The authors evaluated the characteristics of EEG mapping in relation to frequency and amplitude in a group of elderly patients with AD and in a group of healthy elderly control subjects. The former group consisted of 10 patients with AD aged between 65 and 83 years old. The control group included 10 healthy subjects who were matched for age and sex. RESULTS: The spectral analysis of EEG signals relating to frequency and amplitude showed a slowing down of underlying activity in AD patients, with a frequency between 1 and 4 c/sec, amplitudes below 5 microW and no arrest reaction. In healthy subjects spectral analysis showed a signal percentage colocated at a frequency of between 8 and 13 c/sec in relation to frequency. CONCLUSIONS: In view of these results, the authors recommend the use of EEG mapping to complete the diagnosis of Alzheimer's disease in the aged.

[Study of mapped slow auditory evoked potentials in Alzheimer's disease]. / Studio dei potenziali evocati lenti mappati uditivi nella malattia di Alzheimer.

BACKGROUND: Alzheimer's disease affects around 500,000 persons in Italy and its diagnosis remains essentially clinical. Our aim was to contribute to the diagnosis of Alzheimer's disease by mapping auditory evoked potentials (AEP). Evoked potentials represent the electric response of the CNS to an external stimulus and can be represented as a sequence of waves. Brain mapping allows a chromotopogram to be compiled showing chromatic maps. METHODS: A group of 12 patients were studied aged between 68 and 84 years old who were referred to our attention at the Department of Geriatrics and Gerontology at Catania University and the A.O. Cannizzaro, Geriatrics Unit. All patients completed an assessment form (MM-SE, ADAS) and underwent brain NMR and AEP. RESULTS: These tests enabled us to identify two types of patients (Group A and Group B) based on the responses shown. The overall evaluation of results revealed that patients with Alzheimer-type dementia present an anomalous cortical neurogenic response to mapped AEP, and that patients in Group A showed anomalous wave morphology, latency and localisation and asymmetric impregnation. The data gathered in this study did not confirm any specific characteristics of AEP given that similar anomalies are found in metabolic dysfunction syndromes and demyelination pathologies. CONCLUSIONS: However, while it does not constitute a specific technique for screening against Alzheimer's disease, the mapping of AEP may contribute to the diagnosis of this disease.

Treatment of arterial hypertension in the elderly using enalapril.

BACKGROUND: Arterial pressure increases with age and is the most common chronic disease in the elderly, men and women alike. At present arterial hypertension is considered a social disease as it poses great health, economic and social problems. METHODS: A group of 50 patients of both sexes, between 66 and 83 years of age, suffering from essential arterial hypertension and treated with Enalapril administered at doses varying from 10 to 20 mg/day, for a period of 18 months, has been studied. RESULTS AND CONCLUSIONS: The results of this study showed that blood pressure values of almost all the patients treated normalised and left ventricular hypertrophy decreased in all patients with this complication.

Advantages and disadvantages in the therapy with different types of interferon for chronic hepatitis C in the elderly patient.

BACKGROUND: HCV-related hepatitis is a pathology on the increase, and it is especially affecting patients above 60 years old. The only treatment for this disease is therapy with different types of interferon. In this paper the authors compare two of their experiences relative to the treatment of HCV-related chronic hepatitis in the elderly using two types of interferon: recombinant interferon alpha and interferon beta, in order to evaluate their efficacy and side effects. METHODS: The authors studied and compared two groups of elderly patients from Sicily and Calabria receiving medical care in the department of Geriatrics of the University of Catania. The first group consisted of 20 patients with an age ranging between 60 and 69 years, treated with recombinant interferon alpha; the second group consisted of 26 patients aged between 60 and 75 years treated with interferon beta. RESULTS: After an evaluation of the results, the authors argue that recombinant interferon alpha is preferable since the remission percentage is higher (75%). However, the interferon beta therapy proves to be almost without side-effects. CONCLUSIONS: Finally, the authors conclude that even in cases where there could be a possible higher exposure to side-effects linked to the use of recombinant interferon alpha, still, the risk/benefit ratio suggests that recombinant interferon alpha 2b should be used for the treatment of hepatitis in elderly patients, in the light of the results obtained.

About a case of familial adenomatous polyposis.

The authors present a case of FAP, familial adenomatous polyposis. This condition comprises 3 different syndromes characterized by the development of numerous polyps in the colon. Other different expressions of the same genetic anomaly are: familial adenomatous polyposis coli, Gardner's syndrome and Turcot's syndrome. The main risk for these pathologies consists in the frequent cancer outcome, which usually occurs between the 4th and the 5th decade of life and, however, after about 12 years from the first diagnosis. The patient came to the authors' observation in the surgery room of the department of geriatrics, in the university of Catania, where patients from South Italy and Sicily are treated. He had a severe anemic condition and poor general health. At the time of the diagnosis the patient, 56 years old, was subjected to endoscopic investigations which showed extensive polyposis of the entire colon and of the stomach, later on typified as ''Familial polyposis''. He was then subjected to total colectomy and gastric polypectomy. Besides, the patient and his direct family members (4 children and 2 sisters) were also genetically screened. The results proved that the patient and 3 of his children presented a genetic mutation located in connection with one of the two alleles of the APC gene. The potentially cancerous evolution makes it necessary to perform a genetic screening of all direct relatives of patients affected by FAP in order to both uncover the genetic anomaly responsible for this pathology and to prevent cancer, which is the natural outcome of this disease.

Treatment of chronic hepatitis C with lymphoblastoid interferon alpha in elderly patients.

One hundred patients with severe Chronic C Hepatitis, > 60 years of age and a life expectancy > 10 yrs were randomised to receive a course of lymphoblastoid a-IFN or a non specific support therapy as control. Patients randomised to IFN (no. 50) were treated with 3MU i.m. every two days for 2 months and then with 6MU i.m. every second two days for additional 10 months. All patients were followed-up for 12 months at the end of treatment. At the end of treatment, 30/50 patients in the IFN group showed a complete remission with normalisation of ALT and AST values (60%). Partial remission occurred in 11 patients (22%) whose transaminase values improved but did not normalise. No response was seen in 9 cases (18%) who showed similar pre- and post- treatment transaminase levels. On the contrary, normalisation of ALT-AST was observed in just two patients assigned to the non-specific therapy, whereas pre- and post-treatment values were similar in the remaining 48 patients. In patients receiving IFN a marked histological improvement was observed at the end of therapy in 22 responders (73.3%) and in 6 partial or non responders (30%) treated with IFN. No histological improvement was observed in control patients. At the end of the 12-month follow-up (24 months from the beginning of the study), 12 responders relapsed (40%) showing levels of transaminase which returned to the pre-treatment values within the second month from the IFN discontinuation. Therefore 18 out of 50 patients (36%) showed a long-term response to lymphoblastoid interferon. Lymphoblastoid a-IFN is an effective and safe therapy in elderly patients whose life expectancy justify its use and generates responses which are similar to those observed in younger subjects.

Clinical evaluation of the efficacy of pivagabine in the treatment of mood and adjustment disorders.

Depression and distress have in common hypercortisolism, a high turn-over of cerebral monoamines and a wide clinical variability. Results of a clinical open trial with pivagabine (4-[(2,2-dimethyl-1-oxopropyl) amino]butanoic acid, CAS 69542-93-4, Tonerg) on 22 young patients affected by dysthymic disorders and on 38 older patients affected by adjustment disorders following different stressors (mourning, retirement and recovery in institutions of assistance) are reported. Oral treatment with 1800 mg pivagabine lasting 30 days showed in both groups a significant improvement of the psychic state with variations from 50 to 80% of the criteria reported in the Hamilton Rating Scale for Depression (HDRS) and for anxiety (HARS) and in the Self-rating Anxiety Scale (SAS). Good tolerance of the drug and the complete absence of serious side effects considerably contributed to the clinical success.

Preliminary results of beta-interferon treatment in the elderly.

The authors studied 26 patients presenting with chronic hepatitis C who were diagnosed by clinical and histological tests. Thirteen patients were treated with beta-interferon (3 x 10(6) IM for 2 months and consecutive 6 x 10(6) IM for 10 months) every second evening, while the remaining 13 received aspecific treatment. Our results revealed normalization of transaminase accompanied by marked improvement of their clinical and histological pictures in 54 percent of the patients on beta-interferon. All the patients treated with beta-interferon were followed up for a 12-month drug-free period, after which the disease reappeared in 57 percent of the responders.

[Treatment with an aldose reductase inhibitor in peripheral neuropathy in elderly diabetic patients]. / Trattamento con un inibitore dell'aldoso reduttasi nella neuropatia periferica in pazienti diabetici anziani.

Diabetic neuropathy (DN) is one of the most frequent and severe long-term complications in elderly diabetes. Most scientists believe that onset of chronic complications in diabetics is due to prolonged glycometabolic imbalance. Recently aldose reductase inhibitors (ARI) have been used in the treatment of DN. We studied 100 elderly subjects affected by diabetes mellitus who were treated with tolrestat, an ARI, for a year and a control group who received a placebo. All subjects underwent the following examinations at the start of treatment and then at 8, 24, 42 and 52 weeks: 1. electromyography of the lower and upper limbs', 2. biotensiometric evaluation of the vibratory perception threshold (VPT), 3. glycosylated hemoglobin, 4. hourly glycemic profile, azotemia, creatininemia, hemochrome, cholesterol, triglycerides, bilirubin, electrolytes, protidogram, urine. The patients on tolrestat showed: increased nerve conduction velocity (mean values 2.3 m/sec) of the ulnar nerve; increased nerve conduction velocity (mean values 3.9 m/sec) of the peroneal nerve; reduced VPT at the right and left first toe (mean values 5 and 7 volts respectively); reduced VPT at the right and left malleoli (mean values 10 and 8 volts respectively). The authors recommend prompt, long term ARI treatment be initiated before the onset of evident signs of neuropathy in elderly subjects.