Effectiveness of frequency-modulated electromagnetic neural stimulation in the treatment of painful diabetic neuropathy.

AIMS/HYPOTHESIS: The largely unsatisfactory results reported for the pharmacological treatment of diabetic neuropathy has spurred the search for alternative therapies. The aim of this study was to evaluate the efficacy of frequency-modulated electromagnetic neural stimulation (FREMS) as a novel treatment for painful diabetic neuropathy. METHODS: Patients (n=31) with painful neuropathy associated with decreased nerve conduction velocity (<40 m/s) and increased vibration perception threshold (>25 V) were enrolled in a randomised, double-blind, crossover study designed to compare the effects of FREMS with those of placebo. Each patient received two series of ten treatments of either FREMS or placebo in random sequence, with each series lasting no more than 3 weeks. The primary efficacy end point was the change in pain measured by a visual analogue scale (VAS). RESULTS: FREMS induced a significant reduction in daytime and night-time VAS pain score (all p<0.02). Furthermore, FREMS induced a significant increase in sensory tactile perception, as assessed by monofilament; a decrease in foot vibration perception threshold, as measured by a biothesiometer; and an increase in motor nerve conduction velocity (all p<0.01). No significant changes were observed after placebo. Comparison of measurements at the 4-month follow-up with those at baseline revealed that a significant benefit persisted for all measures that showed an improvement at the end of treatment, with an additional improvement in quality of life evaluated by the Short Form-36 questionnaire (all p<0.05). No significant side effects were recorded during the study. CONCLUSIONS/INTERPRETATION: FREMS is a safe and effective therapy for neuropathic pain in patients with diabetes and is able to modify some parameters of peripheral nerve function.

Sleep-disordered breathing in nonobese diabetic subjects with autonomic neuropathy.

To assess the occurrence and nature of sleep-disordered breathing (SDB) in 26 adult, nonobese diabetics (18 with autonomic neuropathy (DAN+) (age 45 (41-50) yrs; body mass index (BMI) 24.1 (22-26) kg x m(-2)) and eight without autonomic neuropathy (DAN-) (age 45 (35-55) yrs; BMI 24.8 (23-26) kg x m(-2))) overnight full sleep studies and measurements of central and peripheral carbon dioxide (CO2) chemosensitivity were performed. DAN+ were divided in two subgroups, according to the presence (DAN+PH+; n=10) or absence (DAN+PH-; n=8) of postural hypotension. Ten normal subjects were studied as controls (age 42 (36-48) yrs; BMI 24.4 (23-25) kg x m(-2)). In contrast to DAN- and controls, who did not show SDB, five DAN+ (four DAN+PH- and one DAN+PH+) had an apnoea/hypopnoea index > or = 10 and four DAN+ (two DAN+PH- and two DAN+PH+) had an apnoea index > or = 5. All the events were obstructive, occurring mainly during rapid eye movement (REM) sleep. Ten DAN+ exhibited a mean lowest oxygen saturation < 90% during REM sleep. No periodic breathing or central sleep apnoeas were found in DAN+PH+, although they had an enhanced central chemoresponsiveness to CO2. Both DAN+ subgroups showed a marked reduction in peripheral CO2 chemosensitivity. In conclusion, adult nonobese diabetics with autonomic neuropathy, independent of the severity of their dysautonomy, have obstructive sleep apnoea/hypopnoea with a frequency > 30%. A decrease in peripheral carbon dioxide chemosensitivity prevents adult nonobese diabetics with autonomic neuropathy and postural hypotension from experiencing posthyperventilatory central sleep apnoea, despite an increased hypercapnic central drive.

[Epidemiology of ischemic cardiopathy in Tuscany]. / Epidemiologia della cardiopatia ischemica in Toscana.

In Italy, parallel to the reduction of mortality due to myocardial infarction over the last 20 years there has been an increase in the overall number of ischemic cardiac patients. The reason for this is that the decline in incidence has been outweighed by an increase both in the number of "survivors" of acute events and in the mean age of the population. In Tuscany in 1997 the principal cause of death, for both sexes, was cardiovascular disease (39.2% of total deaths in males, 23.7% in females). Considering the specific pathologies, in males the principal cause of death was ischemic heart disease (13.5%), while in females it was cerebrovascular disease (17.4%). For the different age-groups, both in males and females cardiovascular disease was the principal cause of death only in the > 74 year age-group, which accounts for by far the greatest number of deaths and thus conditions the statistics, making cardiovascular disease the major cause of death in general. In the period 1987-1998 a progressive reduction in the mortality due to cardiovascular disease and myocardial infarction was observed in both sexes: a comparison of Tuscany with Italy as a whole in 1994 showed lower mortality rates in Tuscany across all the subgroups. Finally, the annual rates of incidence and mortality concerning myocardial infarction in 1998 are analyzed by age-group and, standardized for 100,000 inhabitants, for each of the local healthcare zones in Tuscany.

[Pulmonary hypertension in patients with left ventricular dysfunction studied with contrast-enhanced Doppler echocardiography: relations with diastolic parameters and prognostic implications]. / Studio dell'ipertensione polmonare in pazienti con disfunzione ventricolare sinistra mediante eco-Doppler con contrasto: rapporti con i parametri diastolici e implicazioni prognostiche.

In patients with left ventricular dysfunction, the prognostic value of both pulmonary hypertension and mitral flow patterns has been recognized. However, the effect of the association of different degrees of pulmonary hypertension on prognosis and the corresponding left ventricular diastolic dysfunction is not clear. Accordingly, we considered the impact on survival of a categorization based on the relationship between pulmonary artery pressure and left ventricular diastolic dysfunction, as assessed by mitral and pulmonary venous flow analyses. Transthoracic Doppler echocardiography was carried out in 92 patients with ejection fraction < 45%, pulmonary artery systolic pressure > 25 mmHg and sinus rhythm. Tricuspid regurgitant velocity and Doppler parameters derived from transmitral and pulmonary venous flows were evaluated. In the case of inadequate baseline tracings, weak or poor Doppler signals were enhanced by intravenous injection of a galactose-based contrast agent (Levovist 8 ml suspension at a concentration of 400 mg/ml). To select those whose pulmonary hypertension was either proportional or unproportional to left side filling pressures, patients were divided as follows: Group 1 (n = 69) with low discrepancies and Group 2 (n = 23) with marked discrepancies between Doppler estimates of pulmonary artery systolic pressure and left side filling abnormalities. The patients of each group were also classified according to their mitral flow pattern: abnormal relaxation, pseudonormal and restrictive. Mean pulmonary artery systolic pressure was 49 +/- 16 mmHg in the total population, 43 +/- 11 mmHg in Group 1 and 68 +/- 14 mmHg in Group 2 (p < 0.0001). Several mitral and pulmonary venous flow variables significantly correlated with pulmonary artery systolic pressure in the total population and in the study groups. The best correlations were observed in Group 1 as regards the ratio of reverse-to-forward atrial wave duration (r = 0.83), E wave deceleration rate (r = 0.81), E wave deceleration time (r = -0.81) and the systolic fraction of pulmonary venous flow peak velocities (r = -0.75). In Group 1, the lower heart failure-free survival rate at 10 months was observed in patients with restrictive pattern (68%) as opposed to those with pseudonormal (94%) and abnormal relaxation patterns (97%). The overall heart failure-free survival rate in Group 2 was 86%. In conclusion, the classification according to the relationship between pulmonary hypertension and the alterations of left chamber filling may contribute to the prognostic stratification of patients with left ventricular dysfunction. The patients with pulmonary hypertension proportional to the increase in left chamber filling pressures and restrictive pattern exhibited the worst prognosis.

[Supraventricular tachyarrhythmia of recent onset in the absence of documented cardiac pathology: different therapeutic approaches]. / Tachiaritmie sopraventricolari di recente insorgenza in assenza di patologia cardiaca documentata: differenti approcci terapeutici.

The number of supraventricular tachyarrhythmias recently arisen among patients admitted to the Coronary Care Unit in Piombino, and the results of therapeutical interventions, have been estimated by analysing, retrospectively, the cases pertinent to the period February '84- October '87. Out of 1451 hospitalized patients, the supraventricular tachyarrhythmias were 145; 85 of them (46 F and 39 M, average age 63 +/- 14) with an assured cardiopathy and 60 of them (34 F and 26 M, average age 58 +/- 13) with no assured cardiopathy. The employed drugs, as a first choice, were verapamil, amiodarone or flecainide on the ground of study protocols in order to value their compared effectiveness. When amiodarone was not employed, as a first choice, in conformity with a specific protocol, it was utilized as a second choice after verapamil or flecainide. A DC shock was carried out in the case of pharmacological failure. Among the patients with an assured cardiopathy, the pharmacologically cardioversed ones turn out 55.3%; the spontaneously ones 9.4%; the ones treated by DC shock 14.1%; the non cardioversed ones 21.2%. Among the patients with no assured cardiopathy, the pharmacologically cardioversed ones turn out 78.3%; the spontaneously ones 5%; the treated by DC shock ones 11.7%; the non-cardioversed ones 5%. Therefore, the supraventricular tachyarrhythmias of recent onset make up nearly 10% of the hospitalizations into a Coronary Care Unit; the percentage of cardioversions in a sinusal rhythm with a pharmacological treatment reaches 95% in those patients with no assured cardiopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Exercise tolerance in angina patients 3 and 24 hours after administration of a new delayed-action preparation of metoprolol]. / Tolleranza allo sforzo fisico, in anginosi, a 3 e 24 ore dalla somministrazione di una nuova formulazione "retard" di metoprololo.

To assess the duration of improved exercise tolerance by metoprolol given in a new sustained-release formulation, 40 in-patients affected by stable exercise-induced angina pectoris received single-blind placebo in day 1 and thereafter, in double-blind cross-over once daily administration, metoprolol RETARD 100 mg and 200 mg in days 3 and 5. Symptom-limited cycloergometric exercise tests were performed at 3 and 24 hours after placebo and after each of the two doses of metoprolol RETARD. Duration of exercise, maximal workload and total work performed did significantly increase at 3 and 24 hours after metoprolol RETARD 100 mg (P less than 0.01) and 200 mg (P less than 0.01), without any significant difference between the two doses. Peak systolic arterial pressure and heart rate were lowered by metoprolol RETARD 200 mg at 3 (P less than 0.01) and 24 (P less than 0.01) hours, whereas only the peak heart rate at 3 hours was lowered (P less than 0.05) by the 100 mg dose. It is concluded that in patients with stable exercise-induced angina pectoris, metoprolol RETARD 200 mg appears to be able to increase exercise tolerance and to reduce exercise-induced myocardial oxygen consumption throughout 24 hours period. This may justify a once daily dosing schedule of the 200 mg dose, aimed at improving patient compliance.