Cranial ultrasound is a reliable first step imaging in children with suspected craniosynostosis.

PURPOSE: Skull radiography (SR) and Computed Tomography (CT) are still proposed as the first-line imaging choice for the diagnosis of craniosynostosis (CS) in children with abnormal head shape, but both techniques expose infants to ionizing radiation. Several studies shown that ultrasound may play an important role in the diagnosis of craniosynostosis. The aim of our study is to assess the diagnostic accuracy of cranial ultrasound scan (CUS) and confirm if it is a reliable first step imaging evaluation for the diagnosis of craniosynostosis in newborn. METHOD: A cohort of 196 infants (122/74 males/females), with a mean age of 4 months, clinically suspected to have abnormal closure of cranial sutures, were firstly examined by CUS and then referred to neuroradiologists to perform volumetric CT scan if the suspicion of stenosis was ecographically confirmed; otherwise, a routine follow-up and physical treatment was performed, to observe the evolution of the head shape. RESULTS: Of the 196 children studied by CUS, only two had inconclusive studies due to age limitation (>12 months). Thirty children were diagnosed with cranial synostosis at CUS and verified by CT; all the CUS results were confirmed, except two cases, that were revealed as false positives in the starting phase of the study. Twelve patients with very prominent head deformity and negative CUS underwent CT, which confirmed the CUS results in all of them; one case of closure of both temporal sutures, not studied by CUS, was documented by CT. All the 148 children with poor clinical suspicion and negative CUS underwent just a prolonged clinical follow-up. In all of them, a progressive normalization of head shape was observed, and the craniosynostosis was excluded on a clinical base. CONCLUSIONS: CUS is a highly specific and sensitive imaging technique. In referral centers, expert hands can use it as a reliable first-step screening for infants younger than 1 year, suspected to have a craniosynostosis, thus avoiding unnecessary exposure to ionizing radiation. The "golden age" to obtain the best CUS results is under 6 months of life. Because the method is operator-dependent and there is a learning curve, a case centralization is advisable.

A multicenter observational study on the management of hyperglycemia in patients with acute coronary syndrome.

AIM: To assess the prevalence, risk and management of hyperglycemia in patients with acute coronary syndrome (ACS). DESIGN: a multicenter prospective observational study of a representative sample of patients with ACS consecutively admitted to intensive cardiac care units (ICCU). SETTING: 31 out of 61 ICCUs in Lombardy, the most heavily populated Italian region. From May 2009 to April 2010 1260 patients (69.4% male; mean age 68 ± 13 years) were included in the study: 301 (23.9%) were known diabetic patients (D) and 265 (21.0%) had hyperglycemia (H) (blood glucose >180 mg/dL) at hospital admission, 174 with a history of diabetes (D+H+) and 91 without (D-H+). On the first day after admission intravenous insulin infusion was prescribed to 72 D+H+ (41.4%) and 10 D-H+ (11.0%), according to different protocols. Approximately one third of D+H+ patients (59) and one fifth (17) of D-H+ maintained mean blood glucose higher than 180 mg/dL during the first day in the ICCU. Patients with diabetes or hyperglycemia had a higher incidence of major adverse cardiovascular events or death in hospital. However, at multivariable analysis neither diabetes nor blood glucose at admission was associated with a poor prognosis whereas mean blood glucose on the first day was an independent negative prognostic predictor (OR 1.010, 95% CI 1.002-1.018, p = 0.016). CONCLUSION: Hyperglycemia is frequent in patients with ACS and is independently associated with a poor in-hospital prognosis if it persists in first day. Unfortunately, however, this condition is still poorly treated, with far from optimal blood glucose control.

Adolescents and young adults with type 1 diabetes display a high prevalence of endothelial dysfunction.

AIM: Little is known about endothelial function in adolescents with type 1 diabetes, and we evaluated endothelial dysfunction, using reactive hyperaemia peripheral arterial tonometry (RH-PAT). METHODS: This prospective, observational, 1-year study focused on 73 adolescents with type 1 diabetes, using multiple daily injections or continuous subcutaneous insulin infusion. The subjects were assessed using RH-PAT, body mass index, blood pressure, fasting lipid profile, glycated haemoglobin, insulin requirements and hours of physical exercise per week. RESULTS: Endothelial dysfunction was observed in 56 patients (76.7%), with lower mean RH-PAT scores (1.26 ± 0.22 versus 2.24 ± 0.48, p < 0.0001) and higher glycated haemoglobin values at baseline (8.27 ± 1.24% versus 7.37 ± 0.54%, p = 0.006) and as a mean of the whole period since diagnosis (8.25 ± 1.22% versus 7.72 ± 0.82%, p = 0.034). A higher percentage of patients with endothelial dysfunction showed abnormal cardiac autonomic tests (p = 0.02) and were more sedentary, exercising <4 hours a week, than patients with normal endothelial function. After follow-up in 64/73 patients, we observed endothelial dysfunction in 81.8% of patients, despite a modest improvement in glycated haemoglobin. CONCLUSION: Adolescents with type 1 diabetes displayed evidence of endothelial dysfunction. Good metabolic control (glycated haemoglobin ≤7.5%, 58 mmol/mol) and regular physical activity of at least 4 h a week might be protective.

Echocardiography in clinical practice: the burden of arterial hypertension. A multicenter Italian survey.

Little information is available about the burden of hypertension on echo-lab activity in current practice. The aim of the present nation-wide survey in outpatient echo-labs was to investigate the prevalence rates of (1) echo examinations performed for the evaluation of hypertensive cardiac damage; (2) reports providing quantitative data on left ventricular (LV) structure and geometry; (3) LV hypertrophy (LVH) in hypertensives referred to echo labs. The study was carried out in 14 outpatient echo-labs across Italy. Prescriptions written by general practitioners were used to identify the indications for the examinations. Estimates of LVH were derived from original echo reports or were calculated from LV primary measures, when available, with Devereux's formula in a post-analysis. Echo examination was performed in 2449 subjects (1245 men and 1204 women); hypertension was the indication for echo in 745 (30.4%) cases. In this subgroup, LV mass (LVM), LVM indexed to body surface area, LVM indexed to height(2.7) and relative wall thickness ratio were reported in 58, 59, 54 and 52%, respectively. LVH was present in 53% of untreated hypertensives and, among treated patients, in 45 and 65% of those with and without blood pressure control, respectively. Our findings show that (1) hypertension accounts for approximately one-third of echo examinations performed in clinical practice; (2) a large fraction of echo reports do not provide quantitative data on LVM and LV geometry, (3) LVH is highly prevalent in hypertensives referred to echo labs for assessment of cardiac damage.

Extracardiac organ damage in essential hypertensives with left ventricular concentric remodelling.

Clinical and prognostic values of left ventricular concentric remodelling (LVCR) are based on definition of this cardiac phenotype according to outdated guidelines indications. Thus, we analysed the association of extracardiac organ damage (OD) and LVCR (relative wall thickness >42) as defined by updated diagnostic criteria. Subclinical OD was searched in 1906 patients treated and untreated in essential hypertensives with normal echocardiographic LVMI as defined by two sets of gender-specific criteria based on LV mass (LVM) indexed to body surface area (125 g m(-2) in men and 110 g m(-2) in women) and height(2.7) (49 g m(-2.7) in men and 45 g m(-2.7) in women). Overall, 568 patients (29.8%), fulfilled the criteria for LVCR. Prevalence rates of carotid plaque, carotid intima-media (IM) thickening, grade II retinopathy and microalbuminuria (MA) were significantly higher in patients with LVCR compared with those with normal geometry (53, 24, 22, 10% versus 38, 15, 15, 7%, respectively, P<0.01, at least). Furthermore, an independent association between LVCR and continuous variables of OD such as carotid IM thickness (P<0.0001) and MA (P=0.004) was confirmed by a multivariate analysis. Our results indicate that LVCR identified by updated, less conservative, diagnostic criteria, is strongly associated with subclinical vascular and renal alterations of adverse prognostic significance. These findings support the view that LVCR should be searched for and regarded as a marker of target OD with an additional value for cardiovascular risk stratification in patients with normal LVM.

Indexation of left ventricular mass to body surface area and height to allometric power of 2.7: is the difference limited to obese hypertensives?

Whether left ventricular mass (LVM) should be normalized to different indexes in relation to body size is still debated. We sought to evaluate the prevalence of left ventricular hypertrophy (LVH) defined by different indexation criteria in a cohort of hypertensive subjects categorized according to body mass index (BMI). A total of 2213 essential hypertensive subjects included in the Evaluation of Target Organ Damage in Hypertension (ETODH) were divided in three groups according to BMI thresholds (<25, 25-29.9 and >or=30 kg m(-2)). All patients underwent extensive investigations including quantitative echocardiography. LVH was defined as an LVM index equal to or higher than (1) 125 g m(-2) in men and 110 g m(-2) in women, (2) 51 g m(-2.7) in men and 47 g m(-2.7) in women. Overall, 687 out of 2213 patients (31.0%) were found to have LVH when LVM was indexed to body surface area (BSA) and 1030 (46.5%) when indexed to height(2.7). A total of 845 patients (38.2%) had normal BMI, 954 patients (43.1%) were overweight and 414 (18.7%) were obese. Prevalence rates of LVH in the three groups were 25.1, 31.6, 41.2% by indexation to BSA and 29.9, 50.5, 71.8% by indexation to height(2.7), respectively. LVM indexed to BSA markedly underestimates LVH prevalence in obese as well as overweight hypertensive patients. To avoid a systematic misclassification of cardiovascular risk, LVM should be routinely indexed to height(2.7) in overweight and obese patients representing a large percentage of the hypertensive population.

Metabolic syndrome and biventricular hypertrophy in essential hypertension.

The metabolic syndrome (MS) is associated with structural and functional alterations of the left ventricle (LV); no evidence is available on the impact of the MS on the right ventricle (RV). To assess whether MS, as defined by the ATP III report, is associated with biventricular hypertrophy, a total of 286 hypertensive subjects (mean age 58.7+/-12.2 years) attending our outpatient clinic underwent the following procedures: (1) physical examination and standard clinic blood pressure (BP) measurement; (2) routine laboratory investigations; (3) M-mode, two-dimensional and Doppler echocardiography. LV hypertrophy (LVH) was defined by LM mass index>or=51/47 g m(-2.7) in men and women, respectively. Right-sided chambers were measured in parasternal long axis at the outflow tract and subcostal view; RV hypertrophy (RVH) was defined by anterior RV wall thickness>or=6.0/5.5 mm in men and women, respectively. Filling velocities of both ventricles were assessed by pulsed Doppler echocardiography. Structural cardiac alterations were more pronounced in hypertensive men and women with MS than in their non-MS counterparts and involved both ventricles as shown by the differences in continuous variables as well as in prevalence rates of LVH (58 and 48% vs 28 and 30%, respectively, P<0.01) and RVH (48 and 54% vs 25 and 35%, respectively, P<0.01). Both LV and RV filling in MS hypertensives were more dependent on the atrial systole. Our study shows that in human hypertension, structural and functional cardiac changes induced by MS are not limited to the LV but also involve the right one.

Prevalence and correlates of multiple organ damage in referred treated hypertensives: data from the ETODH study.

This study, carried out in a large cohort of treated essential hypertensives attending an out-patient hospital hypertension clinic, extends previous observations by showing that a clustering of two or three markers of organ damage (OD) has a higher prevalence than a single organ involvement. These findings call for a systematic evaluation of cardiac and extracardiac OD in treated hypertensive patients referred to a specialist setting.

Ambulatory heart rate and target organ damage in never-treated essential hypertensives.

Limited evidence is available about the relationship between ambulatory heart rate (HR) and target organ damage (TOD) in uncomplicated hypertension. We sought to investigate the association between ambulatory HR and subclinical cardiac, vascular and renal markers of TOD in never-treated essential hypertensives. A total of 580 subjects with recently diagnosed (

Different effects of acute administration of aminophylline and nitroglycerin on exercise capacity in patients with syndrome X.

To investigate the effects of the acute administration of aminophylline and nitroglycerin on effort ischemia, 20 patients with syndrome X underwent 3 bicycle exercise tests after sublingual nitroglycerin (0.3 mg) and after 90 minutes of oral administration of aminophylline (400 mg). Compared with the basal test, only aminophylline induced a significant increase in the time to ischemic threshold and to angina; these findings support the potential therapeutic role of this adenosine receptor blocking agents and suggest a possible role of "steal phenomenon" in the pathogenesis of effort angina in patients with syndrome X.

Usefulness of changes in exercise tolerance induced by nitroglycerin in identifying patients with syndrome X.

Two exercise tests, one under basal conditions and one after sublingual nitroglycerin (NTG), were performed in 39 patients with stable angina pectoris--16 with critical coronary stenoses and 23 with normal coronary arteries (syndrome X). Under basal conditions, times at ischemic threshold, at peak exercise, and at complete ECG recovery were similar in the two groups. Peak ST depression was significantly higher in patients with coronary artery disease (CAD). In a similar proportion of patients, ST-segment depression developed earlier or at a low heart rate. Patterns of heart rate, blood pressure, and rate-pressure product during exercise and recovery were also similar. After NTG an increase in the ischemic threshold was observed in a significantly higher proportion of patients with CAD (93.8% vs 39.1%). Furthermore, a subgroup of patients with syndrome X showed a worsening of exercise performance. This suggests that NTG does not directly affect small coronary vessels. Our results confirm that no relevant differences exist in exercise responses between patients with CAD and those with syndrome X under basal conditions. NTG-induced changes in this response could be useful in identifying patients with normal coronary arteries. Moreover, this test could be used as a guide to therapeutic approaches.

[Role of endoscopy in the diagnosis and follow-up of bleeding lesions of the colon]. / Ruolo dell'endoscopia nella diagnostica e nel follow-up delle lesioni sanguinanti del colon.

Considering the results of the centre of colonoscopy we can draw some considerations about the irreplaceable role of endoscopy in the diagnosis of bleeding colonic lesions and about its greater security in comparison with the traditional radiologic exam, about its possibilities to be sometimes resolutive even for the therapy and about its great importance in the follow-up of patients treated for lesions of this kind.

Paradoxical effect of long-term treatment of nifedipine on total ischemic load in patients with stable angina pectoris.

In 50 patients with stable effort angina the effect of three drugs, metoprolol, nifedipine, and diltiazem was assessed by analyzing exercise stress test response and ambulatory ECG recordings. Both metoprolol and diltiazem caused a significant increase in time to ischemic threshold during exercise and a significant decrease of maximum ST-segment depression (during exercise and ambulatory ECG monitoring) and in the average number of daily ischemic episodes. Only metoprolol significantly reduced heart rate and rate-pressure product at the ischemic threshold during exercise. In the group of patients treated with nifedipine no significant improvement was observed in exercise tolerance or in number of ischemic episodes/24 h. Moreover, the subset of nonresponders in the two methods was larger than in the other two groups. In some of these patients a clearcut worsening of total ischemic load was observed, despite the control of symptoms. This adverse effect might be attributed to the different consequences of the vasodilatory effect of nifedipine on blood flow through stenosed vessels.

[Potentiating effect of a supine position on ischemia induced by exercise]. / Effetto potenziante della posizione supina sull'ischemia indotta dall'esercizio.

Though sitting bicycle and treadmill are the commonest devices used in exercise stress testing, supine ergometric test shows some advantages, especially in research investigations. The latter allows better ECG and blood pressure recordings during exercise. Recently, a greater frequency of ST-segment depression has been reported with supine vs upright exercise, but some doubt as to the ischemic significance of this result has been raised. Thus, we compare the ECG and hemodynamic pattern during upright and supine bicycle exercise in 50 subjects with chest pain, without prior myocardial infarction: 31 had documented coronary artery disease (CAD) and 19 had normal coronary vessels. In a subgroup (22 CAD patients and all subjects without CAD) a measurement of myocardial perfusion was performed during exercise using thallium-201 radionuclide ventriculography. Initial work-load and the further graded increases were identical for both postures. The frequency of ST-segment depression was higher during supine exercise (84% vs 74%). The increase in sensitivity (+7% vs CAD) was wider if a more direct measurement of myocardial ischemia was adopted as gold standard (+13% vs TI-201 responses) and was not associated with a decreased specificity (Tab. II). In the supine position the threshold of exercise-induced ST-segment depression was significantly lower. Chest pain appeared more frequently and at a lower work-load. Accentuation and precocity of exercise-induced ischemia in the supine-position could be attributed to an increased imbalance between supply and demand of MVO2 at equivalent work-load, heart rate changes, systolic blood pressure and double product were significantly higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and pharmacodynamics of propafenone during acute and chronic administration.

The pharmacokinetics of propafenone and 5-OH-propafenone and their relationship with the antiarrhythmic action and side effects have been studied in 10 patients with stable, frequent, premature ventricular beats (224-928 premature ventricular complexes/h). Observations were made after a single dose of propafenone 300 mg p.o., and after 1 and 3 months (only 5 out of 10 patients) of therapy with 300 mg t.d.s. After 1 month of treatment the plasma elimination half-life of propafenone (6.7 h) was almost twice as long as after a single dose (3.5 h), and the area under the plasma propafenone concentration-time curve (7620 ng.ml-1.h) was significantly larger than after single dose (3522 ng.ml-1.h); this was also true for the metabolite. The ratio of the AUCs of 5-OH-propafenone and propafenone decreased from the single dose (0.63) to 1 month (0.32). These variables remained stable up to 3 months. Eight patients had greater than or equal to 75% reduction of premature ventricular complexes after 3 days of therapy, and in 7 they were completely suppressed; the response was maintained over 1 to 3 months. Side effects were minor and in no case had the drug to be withdrawn or the dose reduced. Thus, the kinetics of propafenone were time-dependent. Its active metabolite did not accumulate greatly during chronic treatment. The lasting antiarrhythmic effect observed in some patients suggests a b.d.s. regimen instead of t.d.s. dosing in selected patients.

[Usefulness of exertion tests in the evaluation of the effectiveness of antihypertensive therapy]. / Utilità del test da sforzo nella valutazione dell'efficacia del trattamento antiipertensivo.

Aim of this study was to assess the reliability of blood pressure (BP) response to exercise compared with the occasional BP measurements in evaluating the efficacy of an antihypertensive therapy. We have studied 40 subjects (22 M, 18 F mean age 33.3 +/- 6.6) with essential hypertension (19 with mild hypertension, 8 with moderate hypertension, 13 with severe hypertension). Every patient underwent a maximum graded exercise test in the supine position on a bicycle ergometer before starting the antihypertensive treatment. An exercise test was repeated with the same procedure after resting BP had been normalized for at least six months. Both systolic and diastolic BP at peak exercise were significantly reduced (systolic BP from 212.13 +/- 25.79 mmHg to 194.38 +/- 21.58 mmHg; diastolic BP from 128.00 +/- 16.52 to 114.1 +/- 11.02 mmHg) during the second test. An excessive BP increase (above the 95% confidence limits of the BP response to exercise in a group of normotensives) was observed in 32 subjects during the first test. A "hypertensive" response to stress persisted in 13 subjects during the second test even if the resting BP values were normalized. Our data support the value of stress testing in both the evaluation of the hypertensive patient and the assessment of the individual response to treatment.

Reproducibility and reliability of first pass radionuclide ventriculography with Au-195m. Validation of Au-195m radionuclide ventriculography.

Au-195m is a radio-isotope with an ultra-short half-life with which multiple sequential evaluations of ventricular function can be made. In order to evaluate the reliability and reproducibility of analyses of overall and regional ventricular function by radio-isotope ventriculography with Au-195m we studied 10 healthy volunteers and 12 patients with coronary artery disease. Each subject underwent 4 first-pass studies: 1 with Tc-99m and, 10 minutes later, 3 with Au-195m (2 basal studies separated by 3-5 minutes interval and, 10 minutes later, 1 after s.l. nitroglycerin administration). Regional wall motion was analyzed and ejection fraction and peak count rate were determined in each test. Our study showed that the ejection fraction obtained with Au-195m was reproducible (r = 0.98) and correlated well with the ejection fraction determined by using Tc-99m (r = 0.98). The values of the peak count rate obtained with Tc-99m were higher than those obtained with Au-195m. Due to the specially designed collimator and the technical characteristics of the gamma-camera we used, we were able to record sufficiently high count-rates to evaluate regional wall motion, and this analysis was also found to be reliable and reproducible. After s.l. nitroglycerin administration, normal volunteers showed a significant increase of ejection fraction in comparison with basal acquisitions (p less than 0.05), while a wide range of responses was observed in the group of patients with coronary artery disease. We conclude that radio-isotope ventriculography with Au-195m is reliable and reproducible and could be a valid method of monitoring rapid variations induced in overall and regional left ventricular function.