Ultrasound examination for the detection of simulated periapical bone lesions in bovine mandibles: an ex vivo study.

AIM: To evaluate the accuracy of ultrasound examination (USE) for the detection of artificial bone defects in bovine mandibles in the absence of complete erosion of the cortical bone plate and to determine the minimum cortical thickness that constitutes a barrier for ultrasound waves. METHODOLOGY: Sixty bovine mandibular anatomical blocks were harvested and uniformly distributed amongst six experimental groups. The negative control consisted of blocks with no intra-bony defects, whereas the positive control consisted of blocks with an artificial lesion of 2 mm diameter that perforated the buccal cortical bone plate. Two experimental groups comprised blocks with small (2 mm) and large (5 mm) artificial defects created under a cortical plate thinned to varying thicknesses. Two additional groups had small (2 mm) and large (5 mm) artificial defects that did not involve the cortical plate. After USE, the scans were saved and submitted to three blinded examiners. Sensitivity, specificity, predictive values and receiver-operating characteristics (ROC) were analysed. The significance of the findings (P < 0.05) was appraised using the chi-square statistics with the Yates correction, whilst the intra- and inter-examiner agreements were evaluated through Kappa statistics. RESULTS: USE was associated with high sensitivity (97.3%) and negative predictive value (89%), and a perfect score for specificity and positive predictive value. The ROC curve analysis revealed an accuracy of 97.8%. The k-values were 0.86 and 0.89 for the first and second examinations, respectively, demonstrating very high inter-observer agreement. The intra-observer agreement was also high (k-value = 0.92). A significant correlation between the echographic diagnosis and the presence or absence of artificial intraosseous lesions in the anatomical blocks of bovine mandibles was observed (P < 0.0001). CONCLUSIONS: USE was highly accurate and reliable for the detection of artificial lesions within bovine mandibles, regardless of the thickness or presence of the cortical plate.

Perioperative dental screening and treatment in patients undergoing cardiothoracic surgery and interventional cardiovascular procedures. A consensus report based on RAND/UCLA methodology.

AIM: To reach a consensus on a consistent strategy to adopt when screening patients for dental/periodontal infections and on the feasibility of providing dental treatment before cardiothoracic surgery, cardiovascular surgery or other cardiovascular invasive procedures. METHODOLOGY: A panel of experts from six Italian scientific societies was created. The deliberations of the panel were based on the RAND method. From an initial systematic literature review, it became clear that a consensually validated protocol for the reproducible dental screening of patients awaiting cardiac interventions was considered mandatory by professionals with expertise in the dental, cardiologic and cardiac surgery areas. However, a systematic review also concluded that the treatment options to be provided, their prognosis and timing in relation to the physical condition of patients, had never been defined. Following the systematic review, several fundamental questions were generated. The panel was divided into two working groups each of which produced documents that addressed the topic and which were subsequently used to generate a questionnaire. Each member of the panel completed the questionnaire independently, and then, a panel discussion was held to reach a consensus on how best to manage patients with dental/periodontal infections who were awaiting invasive cardiac procedures. RESULTS: A high level of agreement was reached regarding all the items on the questionnaire, and each of the clinical questions formulated were answered. Three tables were created which can be used to generate a useful tool to provide standardized dental/periodontal screening of patients undergoing elective cardiovascular interventions and to summarize both the possible oral and cardiovascular conditions of the patient and the timing available for the procedures considered. CONCLUSIONS: Upon publication of this consensus document, the dissemination of the information to a wide dental and cardiac audience should commence. The authors hope that this consensus will become a model for the development of a dedicated protocol, ideally usable by heart and dental teams in the pre-interventional preparation phase.

Apical periodontitis and cardiovascular diseases: previous findings and ongoing research.

AIM: (i) To discuss the possibility that dental infections in general, and endodontic infections (apical periodontitis) more specifically, may affect cardiovascular health, (ii) which preventive measures should be adopted during the treatment of endodontic infections for infective endocarditis (IE), and (iii) What should be the priorities for future research, in the light of the literature available. METHODOLOGY: A literature review was performed. RESULTS AND CONCLUSIONS: (i) Poor oral health and endodontic infections are associated with cardiovascular diseases, and endodontic infection appears to be associated with initial endothelial damage, (ii) preventive measures for IE should be adopted during endodontic treatment of patients at risk for cardiovascular events according to the American and European available official guidelines, and (iii) more research focused on apical periodontitis and systemic diseases is needed.

Circulating endothelial progenitor cells in postmenopausal women with and without coronary artery disease.

BACKGROUND: Middle-aged women have a lower prevalence of coronary artery disease (CAD) compared with age-matched men, but mechanisms underlying this phenomenon remain controversial. To verify whether there is a link between circulating endothelial progenitor cells (EPCs) and gender-specific difference of CAD, we compared subpopulations of EPCs among postmenopausal normal women, patients with CAD, and age-matched men. METHODS: We studied 71 consecutive middle-aged patients with stable CAD (30 postmenopausal women and 41 men) and 40 middle-aged normal controls (20 postmenopausal women and 20 men). Blood samples were drawn at time of coronary angiography and subpopulations of EPCs were measured by flow cytometry. RESULTS: Women and men with CAD had similar age, risk factors, clinical presentation, left ventricular function, extension of CAD, and medical therapy at time of coronary angiography. Hematologic analysis showed that men and women with CAD had similar white cell count, mononuclear cells, and subpopulations of EPCs. Postmenopausal normal women, conversely, had significantly higher absolute numbers of CD34+, CD133+, CD105+ and CD14+ cells than other groups. CONCLUSIONS: Increased numbers of subpopulations of EPCs in normal postmenopausal women might contribute to the gender-specific difference of CAD in middle age. Lack of difference in EPCs between women and men with CAD suggests that stem cells become unable to play a protective role when the disease is clinically evident.

Perioperative dental screening and treatment in patients undergoing cardio-thoracic surgery and interventional cardiovascular procedures. A consensus report based on RAND/UCLA methodology.

AIM: To reach a consensus on a consistent strategy to adopt when screening patients for dental/periodontal infections, and on the feasibility of providing dental treatment before cardiothoracic surgery, cardiovascular surgery or other cardiovascular invasive procedures. METHODOLOGY: A panel of experts from six Italian scientific societies was created. The deliberations of the panel were based on the RAND method. From an initial systematic literature review, it became clear that a consensually validated protocol for the reproducible dental screening of patients awaiting cardiac interventions was considered mandatory by professionals with expertise in the dental, cardiologic and cardiac surgery areas. However, systematic review also concluded that the treatment options to be provided, their prognosis and timing in relation to the physical condition of patients had never been defined. Following the systematic review several fundamental questions were generated. The panel was divided into two working groups each of which produced documents that addressed the topic and which were subsequently used to generate a questionnaire. Each member of the panel completed the questionnaire independently and then a panel discussion was held to reach a consensus on how best to manage patients with dental/periodontal infections who were awaiting invasive cardiac procedures. RESULTS: A high level of agreement was reached regarding all the items on the questionnaire, and each of the clinical questions formulated were answered. Three tables were created which can be used to generate a useful tool to provide standardized dental/periodontal screening of patients undergoing elective cardiovascular interventions, and to summarize both the possible oral and cardiovascular conditions of the patient and the timing available for the procedures considered. CONCLUSIONS: Upon publication of this consensus document, the dissemination of the information to a wide dental and cardiac audience should commence. The authors hope that this consensus can become a model for the development of a dedicated protocol, ideally usable by heart and dental teams in the pre-interventional preparation phase.

Low testosterone levels are associated with coronary artery disease in male patients with angina.

Historically, high androgen levels have been linked with an increased risk for coronary artery disease (CAD). However, more recent data suggest that low androgen levels are associated with adverse cardiovascular risk factors, including an atherogenic lipid profile, obesity and insulin resistance. The aim of the present study was to evaluate the relationship between plasma sex hormone levels and presence and degree of CAD in patients undergoing coronary angiography and in matched controls. We evaluated 129 consecutive male patients (mean age 58+/-4 years, range 43-72 years) referred for diagnostic coronary angiography because of symptoms suggestive of CAD, but without acute coronary syndromes or prior diagnosis of hypogonadism. Patients were matched with healthy volunteers. Out of 129 patients, 119 had proven CAD; in particular, 32 of them had one, 63 had two and 24 had three vessel disease, respectively. Patients had significantly lower levels of testosterone than controls (9.8+/-6.5 and 13.5+/-5.4 nmol/l, P<0.01) and higher levels of gonadotrophin (12.0+/-1.5 vs 6.6+/-1.9 IU/l and 7.9+/-2.1 vs 4.4+/-1.4, P<0.01 for follicle-stimulating hormone and luteinizing hormone, respectively). Also, both bioavailable testosterone and plasma oestradiol levels were lower in patients as compared to controls (0.84+/-0.45 vs 1.19+/-0.74 nmol/l, P<0.01 and 10.7+/-1.4 vs 13.3+/-3.5 pg/ml, P<0.05). Hormone levels were compared in cases with one, two or three vessel disease showing significant differences associated with increasing severity of coronary disease. An inverse relationship between the degree of CAD and plasma testosterone levels was found (r=-0.52, P<0.01). In conclusion, patients with CAD have lower testosterone and oestradiol levels than healthy controls. These changes are inversely correlated to the degree of CAD, suggesting that low plasma testosterone may be involved with the increased risk of CAD in men.

Epicardial fat thickness, an emerging cardiometabolic risk factor, is increased in young adults born preterm.

Preterm birth and epicardial fat thickness (EFT) constitute novel risk factors for the onset of future adverse cardiovascular events. In total, 30 ex-extremely low birth weight (ex-ELBW) subjects (10 males, 20 females, aged 17-28) were enrolled and compared with 30 healthy peers. EFT was significantly higher (8.7±0.7 mm v. 5.6±0.9 mm; P<0.001) in ex-ELBW than in controls and was correlated with birth weight (r=-0.47, P=0.0009), gestational age (r=-0.39, P=0.03) and cardiac left ventricular mass (r=0.51, P=0.004). When excluding the influence of body mass index, birth weight was the sole remaining determinant of EFT, irrespective of gestational age (r=-0.37, P=0.04). The same findings when excluding the possible influence of blood pressure values on the cardiac structures (r=-0.40, P=0.028). In conclusion, EFT is significantly higher in former preterm subjects and is likewise associated with an increase in left ventricular mass. In view of the acknowledged correlation between the latter and an increased incidence of cardiovascular diseases, EFT appears to be an easy-to-measure tool capable of predicting the likely development of future adverse cardiovascular events in these subjects.

Peripheral dopamine receptors in the antihypertensive action of dihydroergotoxine in humans.

The effect of the intravenous administration of dihydroergotoxine (6 micrograms/kg) on arterial blood pressure, heart rate, and plasma concentrations of norepinephrine and 3,4-dihydroxyphenylacetic acid (the deaminated dopamine metabolite) was studied in 20 subjects with essential hypertension (8 men and 12 women aged 32-68 years old, World Health Organization Class I-II). In supine resting subjects, dihydroergotoxine significantly decreased systolic blood pressure (from 175 +/- 5 to 156 +/- 4 mm Hg; p less than 0.001), diastolic blood pressure (from 109 +/- 4 to 95 +/- 3 mm Hg; p less than 0.001), and heart rate (from 71 +/- 2 to 63 +/- 2 beats/min; p less than 0.001) as compared with the results of placebo treatment. Moreover, dihydroergotoxine reduced plasma levels of norepinephrine (from 368 +/- 39 to 238 +/- 33 pg/ml; p less than 0.001) and 3,4-dihydroxyphenylacetic acid (from 1.57 +/- 0.21 to 1.22 +/- 0.13 ng/ml; p less than 0.01). The time course of the blood pressure decrease paralleled that of plasma norepinephrine concentration. Dihydroergotoxine did not suppress the cardiovascular and plasma norepinephrine concentration. Dihydroergotoxine did not suppress the cardiovascular and plasma norepinephrine response to standing. The effect of domperidone, a peripheral presynaptic dopamine receptor antagonist, on dihydroergotoxine response was studied in six of the 20 subjects (3 men and 3 women 48-64 years old). The intravenous administration of domperidone (0.3 mg/kg) prevented the dihydroergotoxine-induced reduction in blood pressure and heart rate and the fall in plasma norepinephrine and 3,4-dihydroxyphenylacetic acid levels. Domperidone administered alone failed to significantly modify any measured variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac function, physical exercise capacity, and quality of life during long-term thyrotropin-suppressive therapy with levothyroxine: effect of individual dose tailoring.

As recently claimed, TSH-suppressive therapy with L-T4 may have adverse effects on the heart, but these results have not been consistently confirmed. We assessed cardiac function by clinical, echocardiographic, and ergometabolic criteria in 19 patients (16 women and 3 men) receiving long term L-T4 at a fixed daily dose ranging from 1.8-4.0 microg/kg. The results showed significant alterations in several cardiac parameters suggestive of subclinical hyperthyroidism. In particular, intraventricular septum thickness (10.0+/-1.4 vs. 8.1+/-1.1 mm), left ventricular posterior wall thickness (9.4 1.5 vs. 8.1+/-1.1 mm), end-diastolic dimension (47+/-4 vs. 44+/-3 mm), and left ventricular mass index (102+/-15 vs. 75+/-15 g/m2) were significantly increased compared to values in age- and sex-matched euthyroid controls. Exercise tolerance (expressed as maximal tolerated workload; 102+/-14 vs. 117+/-12 watts), maximal VO2 achieved at peak exercise (maximum VO2, 17.3+/-3.3 vs. 21.9+/-2.5 mL/min x kg), and anaerobic threshold (expressed as a percentage of VO2max, 46.5+/-8.4 vs. 56.2+/-6.6) were significantly reduced in L-T4-treated patients. The L-T4 dose was then reduced to the minimal amount able to keep the serum TSH concentration at 0.1 mU/L or less in 7 patients who were reevaluated 6 months after the initial study. This individual tailoring of the TSH-suppressive L-T4 dose was in all cases associated with normalization of all echocardiographic and ergometabolic parameters. In conclusion, our findings show that abnormalities of heart morphology associated with impaired exercise performance occur as a consequence of long term therapy with fixed TSH-suppressive doses of L-T4, but that these abnormalities improve or disappear after careful tailoring of TSH-suppressive therapy.

Effects of acute administration of transdermal estrogen on postmenopausal women with systemic hypertension.

We studied 16 postmenopausal women with mild to moderate hypertension according to a randomized, double-blind protocol. They received patches of transdermal estradiol-17beta rated to deliver 100 mg/day of substance or matched placebo. A 24-hour ambulatory blood pressure (BP) monitoring was performed at baseline and after drug administrations. Our data show that estradiol-17beta exerts beneficial effects, both in lowering elevated BP levels and in maintaining a uniform BP control over 24 hours. Estrogen replacement therapy could be considered when significant changes in BP occur during the postmenopausal period.

Evidence of a role of endogenous estrogen in the modulation of autonomic nervous system.

We studied heart rate variability in 14 healthy women before and after oophorectomy compared with 14 matched women who underwent hysterectomy with ovarian conservation. Surgical menopause induced a decline in cardiac vagal modulation with a shift toward sympathetic hyperactivity. Recovery of the baseline condition after 3 months of estrogen replacement therapy in oophorectomized women suggests a role of estrogen in the autonomic nervous control of the cardiovascular system.

Effects of acute administration of natural progesterone on peripheral vascular responsiveness in healthy postmenopausal women.

Peripheral vascular responses to acute administration of natural progesterone were studied in 12 postmenopausal women (mean +/- SD age 50.3 +/- 4.8 years) with no evidence of cardiovascular disease. According to a randomized, double-blind protocol, all subjects were given natural progesterone as a vaginal cream, able to produce a rapid peak and decay of plasma hormone concentrations, or matched placebo, with crossover after a 1-week washout period. Forearm blood flow and peak flow after ischemic stress (ml/100 ml/min), local vascular resistance (mm Hg/ml/100 ml/min), venous volume (ml/100 ml), and venous compliance (ml/100 ml/mm Hg) were measured by strain-gauge venous occlusion plethysmography at baseline and after progesterone or placebo administration. Plasma norepinephrine concentrations were determined by high-performance liquid chromatography with electrochemical detection. Progesterone sharply decreased forearm blood flow (p <0.01) through an increase in local vascular resistance (p <0.01). Measures of venous function remained unchanged. Although the hormone increased circulating norepinephrine concentrations (p <0.05), there were no significant changes in mean arterial pressure or heart rate. Furthermore, progesterone reduced the local vasodilator capacity, shown by a decrease in forearm delta flow (difference between peak flow and basal flow, p <0.05). Compared with the well-known effect of estrogen, progesterone exerted an opposite action on peripheral vascular responsiveness. Peripheral circulatory changes may be attributed to a direct activity of progesterone on the arterial wall and may in part reflect a modulation of the hormone on peripheral sympathetic tone. Consideration must be given to the hypothesis that the addition of progestin may attenuate the beneficial effects of unopposed estrogen replacement therapy in postmenopausal women.

Study of myocardial contractility by pulsed wave Doppler tissue imaging does not reveal an inotropic effect of estrogen at physiologic dose.

We studied myocardial contractility by pulsed wave Doppler tissue imaging in 6 postmenopausal healthy women. According to a crossover, double-blind protocol, we randomized patients to treatment with transdermal patches of estradiol-17beta or matched placebo. Estradiol-17beta did not modify local systolic and diastolic functions. Thus, at least when acutely administered, estrogen seems to be unable to determine hemodynamic changes at the myocardial level, in opposition to what occurs in the peripheral vascular system.

Cardiac dysfunction in acromegaly: evidence by pulsed wave tissue Doppler imaging.

OBJECTIVE: To verify whether the accuracy of data on myocardial function provided by pulsed-wave tissue Doppler imaging (PWTDI), a new echocardiographic application that allows quantitative measurements of myocardial wall velocities, could help towards a better understanding of the natural history of acromegalic cardiomyopathy. DESIGN: Eighteen patients with active acromegaly (ten men and eight women; mean age 48.0+/-15.0 years) with no other detectable cause of heart disease underwent PWTDI. Thirteen healthy individuals matched for age and body mass index acted as a control group. METHODS: Ejection fraction (EF), transmitral early/late diastolic velocity (E/A) ratio and isovolumic relaxation time (IVRT) were measured by conventional echocardiography; systolic peak (Sv) and early (Ev) and late (Av) diastolic peak velocities, Ev/Av ratio and regional IVRT (IVRTs) were obtained by PWTDI. RESULTS: All patients showed appreciably abnormal left ventricular global diastolic function represented by prolongation of the IVRT (P<0.001). Using PWTDI we found a prolongation of IVRTs and inversion of the Ev/Av ratio. In addition, the Ev/Av ratio proved to be significantly negatively correlated with IVRT; this correlation was not present in the case of the E/A ratio. Furthermore, a decrease in Sv was detected in the basal segment of the lateral wall (P<0.01), which had the greatest degree of diastolic dysfunction. CONCLUSIONS: PWTDI confirmed the acknowledged diastolic dysfunction that accompanies acromegalic cardiomyopathy and highlighted the greater sensitivity of regional PWTDI with respect to global Doppler diastolic indexes. Furthermore, by revealing an impairment of regional systolic function in presence of a normal EF, the findings with PWTDI contradicted the largely accepted theory that systolic function remains normal for several years in patients affected by acromegalic cardiomyopathy.

Estradiol-17beta reduces blood pressure and restores the normal amplitude of the circadian blood pressure rhythm in postmenopausal hypertension.

After menopause, both systolic (SBP) and diastolic (DBP) blood pressure (BP) become higher in women than in men of the same age, suggesting that estrogen deficiency may influence the age-related increase in BP. We studied 30 postmenopausal women (mean age, 55 +/- 5.7 years; time from menopause, 2-5 years) affected by mild hypertension with no target-organ complications by means of 24-h BP monitoring. None of the group were undergoing estrogen replacement therapy or taking antihypertensive drugs. According to a randomized, double-blind protocol, subjects received patches of transdermal estradiol-17beta (E2) or a matched placebo, with crossover after a 7-day washout period. In 12 patients the 24-h peak-to-trough variation in SBP and DBP amounted to less than 10% (nondippers). Administration of E2 significantly decreased 24-h SBP and DBP in the whole cohort (P < .05). Furthermore, E2 restored the expected reduction in BP during nighttime in the nondipper subgroup. It is well known that estrogen replacement therapy protects against the development of both cardiovascular diseases and stroke. Our data suggest that this activity could be attributed, at least in part, to the activity of E2 in preserving physiologic circadian fluctuation of BP.

Extraneuronal noradrenaline in the prefrontal cortex of morphine-dependent rats: tolerance and withdrawal mechanisms.

The changes in extracellular concentrations of noradrenaline (NA) in the prefrontal cortex of morphine-dependent rats were studied by microdialysis following an acute morphine challenge and during naloxone-precipitated withdrawal. Animals were implanted with morphine- or placebo-containing pellets for 5 days. In control rats a challenge dose of morphine (5 mg/kg s.c.) induced a maximum decrease in NA output of about 45% of pre-drug levels. In contrast, morphine challenge had no effect on extraneuronal NA concentrations in morphine-implanted animals. In control animals, naloxone (2 mg/kg i.p.) produced no behavioral effect nor changed NA levels. However, in morphine-dependent animals naloxone suddenly increased extraneuronal NA by 175% of baseline dialysate levels in the first sample after the injection and precipitated a morphine-withdrawal symptomatology that paralleled the changes in NA output. Thus, chronic morphine treatment in rats results in the development of tolerance to the acute inhibitory effect of morphine on extraneuronal NA and is associated with a stimulation of prefrontocortical NA output during naloxone-precipitated withdrawal.

Inhibitory effects of catecholamines in the paravertebral sympathetic ganglia of the anesthetized dog.

alpha-Adrenoceptor agonists decreased mean arterial pressure when injected into the arterial blood supply of the paraspinal sympathetic ganglia of pentobarbital-anesthetized open-chest dogs. The hypotensive response occurred concomitantly with selective decreases of vascular resistance in the vessels innervated by neurons arising from these ganglia, and both of these responses were blocked by the ganglionic blocking agent, hexamethonium. The hypotensive response to phenylephrine was selectively blocked by terazosin; alpha 1 selective agonist, and antagonist, respectively, while the hypotension produced by intra-arterial clonidine was blocked by rauwolscine; alpha 2 selective agonist and antagonist, respectively. Either terazosin or rauwolscine reduced the hypotension produced by noradrenaline or dopamine. These results demonstrated the presence of both alpha 1- and alpha 2-adrenoceptors in the paraspinal sympathetic ganglia. Activation of either alpha-adrenoceptor subtype inhibited ganglionic transmission.

A study of the parameters affecting flow gradient analysis of catecholamines, DOPA and DOPAC by ion pair liquid chromatography with electrochemical detection.

A general method for the determination of norepinephrine, epinephrine, dopamine, 3,4-dihydroxyphenylalanine and 3,4-dihydroxyphenylacetic acid is described. It employs the generation of a flow gradient during the analysis by ion-pair reversed phase liquid chromatography. The method allows a reduction of the analysis time maintaining high resolution of the peaks close to the solvent front. The effect of the flow gradient on column efficiency, detector response and retention are evaluated. The application to specimens of amniotic fluid, urine, human plasma and rat brain tissue is shown.