Autism spectrum disorder and paediatric dentistry: A narrative overview of intervention strategy and introduction of an innovative technological intervention method.

AIM: When treating patients with Autism Spectrum Disorder (ASD) the doctor-patient relationship can be very challenging. The dentist is often forced to work under general anaesthesia or conscious sedation. Children with ASD are patients with an increased risk of caries due to poor oral hygiene, a cariogenic diet and the use of xerostomal drugs. In this work therapeutic strategies used to treat this kind of patients are evaluated and a new method to treat children with ASD is presented in order to increase awareness about this condition in the dental field. METHODS: The Atlas Center (a non-profit organisation in Peurgia, Italy) has developed a software, called paINTeraction, that allows these special children to immerse themselves in a virtual reality with the help of an operator. Through this system the child can explore the dental office (and all its sounds and noises) before the real dental visit, thus connecting to the dental professional, achieving greater compliance and reducing anxiety. CONCLUSION: paINTeraction, with the use of digital technology tools, may be particularly well suited to introduce patients to the therapeutic environment, particularly in the dental setting.

Model based study on monitoring ketone bodies to improve safety in intensive insulin therapy.

AIM: The present study explores new signals (capillary 3betahydroxybutyrate - 3betaOHB) for improving the safety of a closed loop insulin infusion system (external wearable artificial pancreas). METHODS: Data collected during a clinical trial on diabetic subjects including a period of insulin deprivation were interpreted through mathematical models to simulate the effect of monitoring ketone bodies (capillary 3betaOHB, KB) compared to blood glucose in subjects on Continuous Subcutaneous Insulin Infusion (CSII) treatment. RESULTS: The estimation of model coefficients satisfactorily fits experimental data. The evaluation of dynamic changes of capillary 3betaOHB levels showed a more rapid response than blood glucose. CONCLUSIONS: The effect of the combination of monitoring of glucose and ketone bodies can consistently improve the safety and efficacy of the use of a closed loop system for glycemic control in dangerous situations like ketoacidosis. If a subcutaneous glucose-ketone bodies sensor were to become available in the near future it would be a key component of an external artificial pancreas.

Early detection of insulin deprivation in continuous subcutaneous insulin infusion-treated patients with type 1 diabetes.

BACKGROUND: This study was performed to define the clinical relevance of early changes of capillary 3beta-hydroxybutyrate (3betaOHB), for detection of metabolic deterioration before occurrence of overt diabetic ketoacidosis following interruption of continuous subcutaneous insulin infusion (CSII). METHODS: An open clinical trial was performed with eight patients with type 1 diabetes on CSII therapy. After an overnight fast, at 8 a.m. (T0) CSII was interrupted for 4 h. At noon (T240) CSII was re-established, and at 4 p.m. (T480) the study was ended. Blood glucose (BG) and capillary and plasma 3betaOHB were measured at 30-min intervals, plasma insulin at 60-min intervals, and urinary ketones at 120-min intervals. RESULTS: After CSII interruption mean BG increased from 149.8+/-54.4 mg/dL at T0 to 224.8+/-56.2 mg/dL at T240 (P<0.05), and mean capillary 3betaOHB increased from 0.1+/-0.1 mmol/L at T0 to 0.9+/-0.6 mmol/L at T240 (P<0.001). The rate of increase of capillary 3betaOHB was faster and significantly more relevant than that of BG (P<0.05). The restoration of CSII produced a significant reduction of mean BG and capillary 3betaOHB (T480, 119.5+/-24 mg/dL and 0.2+/-0.2 mmol/L, respectively; P<0.05 for both vs. T240). The recovery of capillary 3betaOHB was significantly faster than that of BG (P=0.03). CONCLUSIONS: The dynamic evaluation of changes of capillary 3betaOHB levels can represent a useful support to home BG monitoring in the event of CSII interruption, providing faster information on early metabolic deterioration due to insulin deprivation and allowing preventative action for avoiding the evolution towards overt diabetic ketoacidosis. After reintroduction of insulin infusion the monitoring of the faster recovery of 3betaOHB relative to BG can provide useful information for the prevention of late hypoglycemia due to insulin overinfusion.

Comparison of verapamil versus felodipine on heart rate variability in hypertensive patients.

OBJECTIVE: We evaluated the effect of two calcium channel blockers, verapamil and felodipine, on heart rate variability in hypertensive patients. DESIGN: Time and frequency domain measures of heart rate variability were obtained from 24 h Holter recording in 25 previously untreated hypertensive patients without left ventricular hypertrophy, before and after 3 months of verapamil slow-release treatment (240 mg once daily) or felodipine extended-release treatment (10 mg once daily). RESULTS: Blood pressure values decreased with both drugs. Measures of heart rate variability, comparable at baseline in the two groups, were unchanged after felodipine. After verapamil, the average RR interval, the square root of the mean of the squared differences between all adjacent normal RR intervals (r-MSSD) and the percentage of differences between all adjacent normal RR intervals > 50 ms (pNN50), measures of vagal modulation of heart rate, increased (from 735 +/- 67 to 827 +/- 84 ms, P < 0.001; from 30 +/- 10 to 44 +/- 15 ms, P < 0.001; and from 3 +/- 2 to 7 +/- 6%, P < 0.01, respectively) and were higher than after felodipine. The coefficient of variation, a measure that compensates for heart rate effects, increased only after verapamil (from 5.8 +/- 1.3% to 6.6 +/- 1.0%; P < 0.05). High frequency power and its coefficient of component variance, both representing the vagal modulation of heart rate, increased after verapamil (from 5.33 +/- 0.29 to 5.80 +/- 0.27 In units, P < 0.001 and from 1.9 +/- 0.3 to 2.2 +/- 0.25%; P < 0.05). Finally, the low to high frequency power ratio, an indicator of sympathovagal balance, with a high value suggesting a sympathetic predominance, decreased after verapamil (from 2.16 +/- 0.41 to 1.36 +/- 0.35; P < 0.001), confirming the improvement in vagal modulation of heart rate. CONCLUSION: In hypertensive patients, despite a comparable anti-hypertensive effect, verapamil, but not felodipine, has favourable effect on cardiac autonomic control.

Twenty-four-hour blood pressure monitoring during treatment with extended-release felodipine versus slow-release nifedipine in elderly patients with mild to moderate hypertension: a randomized, double-blind, cross-over study.

OBJECTIVE: This double-blind, placebo-controlled randomized study was designed to compare the antihypertensive effect and tolerability of extended-release felodipine and slow-release nifedipine retard in elderly hypertensive patients. METHODS: Thirty patients of both sexes (mean age 71 years) with mild to moderate essential hypertension were recruited from our hypertension outpatient clinic. After a 2-week placebo period, felodipine extended-release (felodipine ER), 10 mg once daily, nifedipine slow-release retard (nifedipine SR), 20 mg twice daily or placebo were administered to each patient for 2 weeks according to a 3 x 3 latin-square design. At the end of each treatment period, the patients underwent 24-h noninvasive blood pressure monitoring. RESULTS: All of the patients completed the trial and no serious adverse experience was reported. In comparison with placebo, felodipine and nifedipine decreased mean 24-h diastolic blood pressure by 6.7 and 4.3 mmHg, respectively, with no significant difference between the two drugs. Mean 24-h systolic blood pressure also decreased after felodipine and nifedipine, with no difference between the two drugs. Both drugs reduced blood pressure variability, lowering the 24-h mean standard deviation of mean hourly blood pressure values. The trough:peak ratio for felodipine was 80% for systolic and 75% for diastolic blood pressure. CONCLUSION: Felodipine ER once daily lowers blood pressure in elderly hypertensives and is as effective as nifedipine SR twice daily. The high trough:peak ratio suggests that the dose and the between-dose interval of felodipine provides adequate therapeutic coverage.

Quinapril versus lisinopril in the treatment of essential hypertension in elderly patients with low blood renin. / Quinapril verso lisinopril nel trattamento dell'ipertensione essenziale in pazienti anziani con bassa reninemia. Nota di terapia.

The aim of the study was to evaluate efficacy and tolerability of quinapril 20 mg once-a-day versus lisinopril 20 mg, in the treatment of old patients suffering from essential mild or moderate hypertension and presenting low levels of plasmarenin. It was a cross-over study with open treatments randomly assigned. Ten patients were treated, 6 females and 4 males, with average age of 67.1 years +/- 7.1. Two wash-out periods with placebo were scheduled, each lasting one week before the onset of active therapy; each treatment period lasted 21 days. Blood pressure controls (including the 24 hours monitoring) were done at basal time, after seven days and at the end of each treatment. Results show the efficacy and the safety of both the drugs and a more effective and constant control of hypertension by Quinapril was confirmed.

Influence of left ventricular hypertrophy on heart period variability in patients with essential hypertension.

OBJECTIVE: To evaluate whether left ventricular hypertrophy in hypertensive patients is associated with a greater impairment of sympathovagal balance assessed by means of heart period variability. DESIGN AND METHODS: Forty hypertensive patients, 20 with echocardiographic evidence of left ventricular hypertrophy and 20 without, and 20 control subjects, were subjected to 24 h blood pressure monitoring and Holter recording on 2 consecutive days. Power spectrum analyses of heart period variability were performed utilizing the fast Fourier transform algorithm. RESULTS: No difference was detectable in 24 h, daytime and night-time blood pressure values between hypertensive patients with and without left ventricular hypertrophy. Low- and high-frequency powers were higher in controls than in hypertensives; in particular, low-frequency power showed a progressive decrease through control subjects and hypertensives without and with left ventricular hypertrophy. Furthermore, significant negative correlations were found between left ventricular mass index and low- and high-frequency power. No difference was detectable in ultra-low- and very low-frequency power. During daytime low- and high-frequency power were higher in controls than in hypertensives; during night-time, low- and high-frequency power increased significantly in all groups and low-frequency power was still higher in control subjects. CONCLUSIONS: Considering that, when analysed over 24 h Holter recording, low- and high-frequency power both reflected the parasympathetic modulation of heart rate, the present results demonstrate a parasympathetic withdrawal in hypertension; this sympathovagal imbalance is greater in patients with cardiac hypertrophy and is related to the increase in left ventricular mass.

Effects of age and hypertension on adrenoceptor-sensitivity evaluated with CD25 and QT/QS2.

BACKGROUND: We studied the effects of age and hypertension on responses to chronotropic dose (CD25) and standing-induced changes in the ratio of electrical systole (QT) to electromechanical systole (QS2) in order to identify their role on beta adrenoceptor sensitivity and to verify the value of QT/QS2 ratio as a noninvasive parameter of beta-adrenoceptor sensitivity. METHODS: We enrolled 33 normal subjects and 37 hypertensive patients (WHO stage I and II) (age range 21-82 years). RESULTS: CD25 was significantly age-related in normotensive and hypertensive subjects, whereas standing-induced QT/QS2 changes were age-related in normotensive subjects only When we divided subjects into three age groups, beta-adrenoceptor sensitivity was found to be lower in hypertensives than normotensives in the two groups under age 60, but was not affected in those over age 60. This suggests that hypertension influences beta-adrenoceptor sensitivity in younger subjects, but not in elderly patients, whose beta-adrenoceptor sensitivity is already reduced. CONCLUSIONS: CD25 does not predict standing-induced QT/QS2 ratio changes; therefore, during autonomic stimulation, QT/QS2 ratio seems not to be significantly related to beta adrenergic sensitivity.

[Efficacy and tolerance of aniracetam in elderly patients with primary or secondary mental deterioration]. / Efficacia e tollerabilità dell'aniracetam in pazienti anziani affetti da deterioramento mentale primitivo e secondario.

The study was carried out on 60 patients (mean age 69.9 +/- 10.3 years) suffering from slight-moderate brain pathology primary or secondary to vascular forms. Patients were treated with 1500 mg/day per os of Aniracetam or placebo. Drug efficiency evaluation was performed utilizing the following psychometric tests: Blessed Scale, figures repetition test, Benton test, Corsi test, Rey test, Pieron test, phrases construction test, verbal fluency test. They were carried out during basal visit after two and four month treatment. In Aniracetam treated group the score showed a significant improving during the first and second control. In placebo treated group no change statistically considerable happened in any test. Aniracetam has proved to be a useful drug in slight-moderate brain decay treatment of the elderly.

[Influence of age on the short- and medium-term prognosis in patients with acute myocardial infarct]. / Influenza dell'età sulla prognosi a breve e medio termine nei pazienti con infarto acuto del miocardio.

Elderly patients with acute myocardial infarction (AMI) have a higher subsequent mortality than younger ones, yet the reasons for this adverse prognosis are poorly understood. We compared the clinical course and the prognosis of 163 patients aged 40 to 69 years with 112 patients older than 70 years. During hospitalization period 15.9% of younger and 37.5% of older patients died; at 1 year follow-up the cardiac mortality rate was 8.7% in younger and 12.9% in older patients. In elderly patients a greater prevalence of female gender, diabetes mellitus, anterior myocardial infarction, atrial fibrillation and a greater incidence of heart failure and shock were observed. Multivariate stepwise analysis identified shock and heart rate greater than or equal to 90 bpm at the time of admission as the most important prognostic variables for in-hospital mortality in both groups; heart failure (Killip class II and III) was significant in younger patients, while non Q wave myocardial infarction correlated with a better prognosis in elderly. In elderly patients who survived AMI, predischarge Holter monitoring showed higher frequency and complexity of ventricular arrhythmias, and radionuclide angiography lower left ventricular ejection fraction (E.F.) values. In these patients no difference was found in E.F. values despite myocardial infarction sites. At 1 year follow-up E.F. less than 40% and ventricular arrhythmias (3-4 Moss grading system) were significantly related to prognosis in younger patients, while E.F. less than 40% and clinical signs of heart failure in elderly. Therefore, low E.F. and heart failure account for a worse prognosis in elderly patients, while ventricular arrhythmias in younger ones. The results of this study support aggressive management even in elderly patients following AMI to preserve left ventricular function. In elderly patients a large use of antiarrhythmic drugs is not recommended because of low prognostic value of ventricular arrhythmias.

[The clinico-instrumental evaluation of the efficacy of picotamide in treating chronic obstructive arteriopathies of the lower extremities]. / Valutazione clinico-strumentale della efficacia della picotamide nel trattamento delle arteriopatie croniche ostruttive degli arti inferiori.

In 25 patients (19 males and 6 females) suffering from chronic arteriopathy of lower extremities at Fontaine stage II, the clinical efficacy of picotamide was investigated in double blind, cross over placebo-controlled study. Patients were assigned randomly to the treatment with placebo or picotamide (900 mg/die) for three months and, after 15 days of wash-out, to the treatment with picotamide or placebo for the same period. Painfree walking distance and ankle/arm systolic pressure ratio improved significantly only during picotamide treatment. Laboratory monitoring revealed a significant decrease in platelet aggregation and an increase of fibrinogen degradation products only during picotamide treatment. Three patients during picotamide treatment referred transient gastrointestinal discomfort (nausea, vomiting and diarrhoea); however in no case the treatment was suspended because of the appearance of these symptoms. These results indicate that picotamide is an effective drug in the management of chronic arteriopathy of lower extremities.

[The effects of slow-release verapamil in relation to plasma concentration in aged hypertensives. A study with continuous monitoring of arterial pressure and electrocardiogram]. / Effetti del verapamil slow release negli ipertesi anziani in rapporto alle concentrazioni plasmatiche. Studio mediante monitoraggio continuo della pressione arteriosa e dell'elettrocardiogramma.

Twenty-four hour ambulatory blood pressure and electrocardiographic monitoring (Oxford method) was carried out in baseline conditions and after 15 days of therapy with a once a day administration of 240 mg verapamil slow-release in 11 elderly hypertensive patients. The 24 hour electrocardiographic monitoring (but not the blood pressure monitoring) was also carried out after 30 days of therapy. High-pressure liquid chromatography plasma concentrations of verapamil and its metabolite norverapamil were compared with the blood pressure and electrocardiographic responses. Systolic and diastolic blood pressure were significantly reduced after 15 days of therapy without circadian rhythm modification; mean heart rate was reduced after 15 and 30 days and the P-Q interval prolonged. Peak verapamil and norverapamil plasma concentrations were observed 8 hours after administration; at the 25th hour, the concentrations were respectively 60.9% and 68.3% of peak value (139.5 +/- 95.4 ng/ml and 126.4 +/- 60.9 ng/ml). Plasma levels of verapamil and norverapamil significantly correlated with heart-rate decrease. No correlation was observed between drug concentrations and systolic and diastolic blood pressure. A first-degree atrioventricular block was observed in 3 patients during therapy. Supraventricular premature contractions showed a decrease after 15 and 30 days of therapy. Thus, once a day administration of verapamil slow release is an effective anti-hypertensive medication in elderly hypertensive patients. Caution should be exercised in patients with P-Q interval prolongation and sinus bradycardia.

Differences in blood pressure profile between young and elderly hypertensive patients.

We studied 40 subjects, 20 under 60 yrs old (10 normotensive and 10 hypertensive) and 20 over 60 yrs old (10 normotensive and 10 hypertensive). Each patient underwent a 24-hour ambulatory blood pressure monitoring (8:00 a.m. to 8:00 a.m.), by a noninvasive method using an ICR 5300 apparatus. Systolic blood pressure was significantly higher on random measurement and during the daytime in the older patients. Although comparison of the other parameters did not reveal significant differences, we noted a tendency to higher systolic values among the older group, and higher diastolic values in the younger one. The variability of the values was slightly higher, although not significantly, among the older patients. In both groups random systolic measurements, and in the younger group diastolic values as well, were significantly higher than mean 24 hour values. The incidence of abnormal systolic BP values ranged from 18.8% to 100% (mean 60.2% +/- 28.9) in younger hypertensives, and from 54% to 100% (mean 76.5% +/- 14.4) in older patients. The incidence of abnormal diastolic BP values ranged from 64.5% to 100% (mean 80.4% +/- 15.6) in younger patients and from 47.2% to 96% (mean 67.8% +/- 15.8) in older patients. The correlation between mean systolic and diastolic values recorded from 8:00 to 10:00 a.m., and mean 24-hour values was significant in young hypertensives, while in the older group there was a significant correlation only for diastolic BP. The lack of significance for systolic values is probably due to a greater variability in systolic pressure in elderly subjects during the morning.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation at midterm of the clinico-instrumental efficacy and tolerance of picotamide in patients with obliterative arteriopathy of the lower limbs]. / Valutazione a medio termine dell'efficacia clinico-strumentale e della tollerabilità della picotamide in pazienti affetti da arteriopatia obliterante degli arti inferiori.

After a 4-week wash-out period, picotamide was administered to 25 patients affected by chronic arteriopathy of the lower limbs (scale 2 according to Fontaine) at a dose of 900 mg/die for 90 days, and then at a dose of 600 mg/die for a further 90 days, in order to assess its efficacy according to the following parameters: duration of gait, residual pressure index (RPI) resting the ankles, hematochemicals, electrocardiogram. At the end of the study a statistically significant increase was observed in the duration of gait and RPI at the ankles and, of the hematochemical parameters, in an increase in fibrogenic degradation products. Adverse reactions were only observed in 3 patients and regressed spontaneously. In conclusion, picotamide was found to be efficacious in patients affected by chronic obliterating arteriopathy of the lower limbs with the possibility of reducing the dose after 3 months of therapy.

[Cardiotoxicity of local anesthetics: dynamic electrocardiogram study]. / Cardioteossicita degli anestetici locali: studio mediante elettrocardiogramma dinamico.

Twenty-two cardiopathic patients (mean age 54.4 +/- 9.9 years) underwent dynamic electrocardiography during tooth extraction under local anesthesia (mepivacaine hydrochloride 2% plus adrenalin 1:200.000). Heart rate (p less than 0.001), systolic and diastolic blood pressure (p less than 0.001) significantly increased during tooth extraction returning to values near to basal level in the recovery period. No patients showed significant changes in ST segment. One patient with chronic atrial fibrillation presented an increase in ventricular rate (180 beats/min) and appearance of premature ventricular beats, spontaneously regressed. In conclusion, in cardiopathic patients dental operations by local anesthesia with vessel constriction it is possible, provided estimated clinical conditions of patients.

Effects of aging and beta-adrenergic-blockade on standing-induced QT/QS2 changes.

In order to evaluate whether the changes in the electrical systole/electromechanical systole ratio (QT/QS2) may reflect the effects of beta-adrenergic stimulation on the heart, we studied the variations of this ratio induced by active standing. We studied 45 healthy volunteers aged 15 to 82 years, subdivided into three groups; Group 1 (mean age 22 +/- 4 years), Group 2 (mean age 44 +/- 6 years), and Group 3 (mean age 74 +/- 6 years). Fifteen subjects repeated the test after propranolol administration (0.1 mg/kg iv). Resting QT/QS2 ratio increased slightly, but not significantly, with age. Upright position significantly increased QT/QS2 ratio in all groups. Changes in heart rate (r = -.43), electromechanical systole (r = .55) and QT/QS2 were significantly correlated with age. Propranolol prevented the increase in QT/QS2 ratio induced by active standing. Therefore, QT/QS2 changes induced by standing are correlated with age and are inhibited or reduced by beta-blockade. QT/QS2 changes can be used to monitor adrenergic activity, even if their value is limited by the overlapping responses of the individual cases.

Regional coronary hemodynamic effects of diltiazem in man.

We evaluated the changes in regional coronary hemodynamics induced by diltiazem, 0.25 mg/kg intravenously, in nine patients with 75% to 90% diameter stenosis of the left anterior descending coronary artery (LAD) (group 1) and in 10 patients with 100% occlusion of the LAD and collaterals to the distal LAD (group 2). Although diltiazem induced similar changes in systemic hemodynamics in the two groups, a decrease in anterior coronary vascular resistance (ACVR) and an increase in great cardiac vein flow (GCVF) were observed after administration of diltiazem in all patients in group 1 but in only 6 of 10 patients in group 2 (subgroup 2B). ACVR increased and GCVF decreased after administration of diltiazem in 4 of 10 patients in group 2 (subgroup 2A). Clinico-angiographic characteristics, origin of collaterals, and diltiazem-induced changes in systemic hemodynamics were similar in subgroups 2A and 2B. Thus diltiazem increases coronary flow distal to a stenotic coronary artery but can decrease regional coronary flow and increase regional coronary resistance in a minority of patients with an occluded coronary artery supplied by collaterals, probably through a steal mechanism.

Role of increased cholinergic activity in reperfusion induced ventricular arrhythmias.

The effect of increased cholinergic activity on reperfusion induced ventricular arrhythmias was studied in alpha chloralose anaesthetised dogs by administering neostigmine during a 25 min occlusion of the anterior left descending coronary artery. The dogs were divided into five groups, each of 10 animals: the control group received only saline solution; group 1 neostigmine 0.03 mg.kg-1 iv at 20 min of coronary occlusion (that is, 5 min before reperfusion); group 2 atropine 0.4 mg.kg-1 iv at 10 min of coronary occlusion and neostigmine 0.03 mg.kg-1 iv at 20 min; and group 3 neostigmine 0.03 mg.kg-1 iv at 20 min of coronary occlusion and at the same time underwent atrial pacing at the same rate as that of the sinus node just before neostigmine administration. In group 4 heart rate was slowed (junctional rhythm) by destroying the sinus node at 20 min of coronary occlusion. The results obtained showed that ventricular tachycardia and fibrillation, which occur at the beginning of reperfusion, were significantly less frequent in group 1 (p less than 0.001) and in group 4 (p less than 0.001). The protective action of neostigmine was abolished by previous administration of atropine (group 2) and modified by preventing the decrease in the heart rate by atrial pacing (group 3). In group 3 ventricular tachycardia was more frequent but the incidence of ventricular fibrillation was reduced significantly compared with the control and atropine groups. Thus cholinergic activity has a protective role in reperfusion arrhythmias by decreasing the heart rate before release of the coronary occlusion and therefore reduces the incidence of ventricular fibrillation.