Anti-resorptive therapy and MRONJ. A survey of the Italian Society of Periodontology and Implantology.

OBJECTIVES: Anti-resorptive agents have been linked to the development of MRONJ in patients undergoing dental surgical procedures. This survey aims to explore the level of knowledge and experience of Italian Society of Periodontology and Implantology members in the management of patients treated with anti-resorptive agents and with the risk of developing MRONJ. MATERIALS AND METHODS: An 18-item questionnaire was submitted by e-mail to the SIdP members. Statistical analyses were carried out. Continuous variables were described as mean ± standard deviation (SD) or median, and first and third quartile according to distribution's normality. Normality of data was checked with Shapiro-Wilk test. RESULTS: Four hundred and fifty-one questionnaires were returned by e-mail (32%). Most of the respondents were private practitioners (81.8%). Only 47.7% declared to be highly confident in managing patients on anti-resorptive therapy while 92.5% reported to have performed tooth extractions and 52.3% implant surgery in patients under anti-resorptive therapy for osteometabolic disorders. One or more MRONJ-affected patients were encountered by 63.2% of the respondents. CONCLUSIONS: This survey highlights the need to develop a "dedicated" program both for dentists and prescribers to improve the level of cooperation and to increase the level of awareness of patients treated with anti-resorptive agents.

Anti-resorptive therapy in the osteometabolic patient affected by periodontitis. A joint position paper of the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP).

This joint report from the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP) aims for a consensus around the scientific rationale and clinical strategy for the management of osteoporotic patients affected by periodontitis who are undergoing anti-resorptive (AR) therapy to manage the risk of the occurrence of a medication-related osteonecrosis of the jaws (MRONJ). Osteoporosis and periodontitis are chronic diseases with a high prevalence in aging patients, and they share some of the same pathogenetic mechanisms based upon inflammation. Available evidence shows the relationship among osteoporosis, AR agents, periodontitis and implant therapy in relation to the incidence of MRONJ. Uncontrolled periodontitis may lead to tooth loss and to the need to replace teeth with dental implants. Tooth extraction and surgical dental procedures are recognized as the main risk factors for developing MRONJ in individuals taking AR therapy for osteometabolic conditions. Although the incidence of MRONJ in osteometabolic patients taking AR therapy may be as low as 0.9%, the increasing prevalence of osteoporosis and the high prevalence of periodontitis suggest that this potential complication should not be overlooked. Good clinical practice (GCP) guidelines are proposed that aim at a more integrated approach (prescriber, dentist, periodontist and dental hygienist) in the management of periodontitis patients undergoing AR therapy for osteometabolic disorders to reduce the risk of MRONJ. Dental professional and prescribers should educate patients regarding the potential risk associated with the long-term use of AR therapy and oral health behavior.

3D passive stabilization of n = 0 MHD modes in EAST tokamak.

Evidence is shown of the capability of non-axisymmetrical conducting structures in the Experimental Advanced Superconducting Tokamak (EAST) to guarantee the passive stabilization of the n = 0 MHD unstable mode. Suitable numerical modeling of the experiments allows a clear interpretation of the phenomenon. This demonstration and the availability of computational tools able to describe the effect of 3D conductors will have a huge impact on the design of future fusion devices, in which the conducting structures closest to plasma will be highly segmented.

Perioperative management of four anaemic female Jehovah's Witnesses undergoing urgent complex cardiac surgery.

Previous studies have demonstrated that preoperative haemoglobin concentration and female gender are related to an increased need for perioperative allogeneic transfusions in cardiac surgery. Hence, urgent cardiac surgery presents a dilemma for female patients who are Jehovah's Witnesses, because of their refusal of allogeneic transfusion. This report describes the management of four high-risk anaemic female patients undergoing urgent complex cardiac surgery. In these Jehovah's Witness patients, strict application of a comprehensive blood-sparing protocol permitted safe avoidance of allogeneic transfusions. The protocol involved intraoperative acute normovolaemic haemodilution, intraoperative administration of tranexamic acid, intra- and postoperative use of a cell-saver system, postoperative administration of erythropoietin, iron and folic acid, and a careful surgical technique to avoid perioperative bleeding.

Entacapone improves the pharmacokinetic and therapeutic response of controlled release levodopa/carbidopa in Parkinson's patients.

The aim of this trial was to evaluate the effects of the COMT inhibitor entacapone on both the pharmacokinetic profile and clinical efficacy of controlled release levodopa in Parkinson's disease (PD) patients. Twelve PD patients experiencing "end-of-dose" type motor fluctuations were evaluated in this single-blind, randomized cross-over study. A single dose of either entacapone (200 mg) or placebo was co-administered with controlled release levodopa. Blood samples were taken every 30 minutes for 3 hours, and in 6 patients, sampling was continued for a further 3 hours. The clinical response to treatment was evaluated using the Unified Parkinson's Disease Rating Scale motor score. Addition of entacapone to levodopa treatment prolonged the "on" phase of the PD patients by 37% (p<0.05). This increased duration of 'on' time was concomitant with a significant increase in levodopa bioavailability (AUC). These data confirm the ability of entacapone to enhance the clinical efficacy of controlled release levodopa formulations, and provide further evidence that entacapone is of value in extending the benefits of levodopa in PD patients experiencing motor fluctuations.

Subcutaneous continuous apomorphine infusion in fluctuating patients with Parkinson's disease: long-term results.

Fluctuations in motor disability and dyskinesias are the major problem in the long-term treatment of Parkinson's disease (PD). Many authors and ourselves have shown that by giving patients a continuous infusion of levodopa it is possible to control motor fluctuations. Levodopa can be administered continuously only by intravenous, intragastric or intrajejunal delivery. Continuous dopaminergic stimulation can be achieved more easily by infusing dopamine agonists subcutaneously. Apomorphine is a potent water-soluble dopamine receptor agonist that has been shown to successfully control motor fluctuation when subcutaneously infused in complicated parkinsonian patients. We report the clinical data of 30 PD patients having at least five years of treatment with subcutaneous continuous apomorphine infusion.

Primary cardiac tumors: early and late results of surgical treatment in 91 patients.

BACKGROUND: Between March 1980 and September 1997, 91 patients underwent evaluation and treatment for primary cardiac neoplasms. METHODS: Tumors were grouped into three categories: atrial myxomas, benign nonmyxomas, and malignant tumors. Survivors were contacted; no one was lost to follow-up. The mean follow-up for this series is 7 +/- 5 years. RESULTS: Eighty-three patients were diagnosed with atrial myxomas (Male/Female: 29/54), average age 55 +/- 13 years. The hospital mortality was 3.6% (3/83), the late mortality was 6.5% (5/80). No recurrent myxomas have been identified clinically or by echocardiography in any patient. Three patients were diagnosed with benign nonmyxoma tumors. (Male/Female: 2/1), average age 64 +/- 8 years. There were no perioperative deaths and 1 patient died 4 years postoperatively from fibroma, with no linked causes. No recurrent tumors have been identified. Five patients were diagnosed with malignant tumors. (M/F: 1/4), average age 53 +/- 16 years. The hospital mortality was 20% (1/5); in 3 patients a redo-operation was necessary after 8, 11, and 12 months because of tumor recurrence. All patients died within 3 years of the first operation (mean 13 +/- 14 months). CONCLUSIONS: Surgical resection, when possible, is the treatment of choice for all primary cardiac tumors. Patients with benign tumors are probably cured by resection and in our experience there was no known tumor recurrence. Effective palliation is possible with resection of malignant tumors, but more effective adjuvant therapy will be necessary to improve long-term prognosis.

Left atrial approach to big myxoma with angiographically visible neovascularity. Report of one case.

In this article, we report a 65-year-old man with a large atrial myxoma arising from the posterior wall and from the base of the right inferior pulmonary vein. The big neoplastic mass showed a large implant site. A rare atrial myxoma neovascularity arising from the atrial circumflex artery was very clearly visualized by selective coronary arteriography. The surgical approach used to resect this tumor was an isolated left atriotomy that provided excellent exposure and safe excision.

Atrial septal defect and pregnancy: a retrospective analysis of obstetrical outcome before and after surgical correction.

STUDY OBJECTIVES: To describe the obstetrical outcome and long-term cardiac follow-up of a group of patients who had surgery for atrial septal defect repair before pregnancy and a group who underwent pregnancy before surgical correction. DESIGN: Retrospective. SETTING: Public Institution. PATIENTS: Eighty women (mean age 20.15 +/- 4.5 years) complaining of atrial septal defect, 60 of which had surgical correction before pregnancy and subsequently had 115 pregnancies, and 20 of which underwent pregnancy before the correction of cardiac defect and subsequently had 48 pregnancies. INTERVENTIONS: Surgical correction of atrial septal defect: 49 by open heart technique (13 with cardiopulmonary bypass, 36 with light hypothermic circulatory arrest), 11 by closed heart techniques. RESULTS: Patients who underwent pregnancy before surgery had an increased incidence of miscarriage, pre-term delivery and cardiac symptoms during pregnancy. Patients operated before pregnancy required more frequently cesarean section and pharmacological therapy. The frequency of stillbirths, malformations in the offspring and long-term cardiac complications were similar in both groups. CONCLUSIONS: Surgical correction of atrial septal defect before pregnancy is recommended even in case of apparently well compensated hemodinamic situation for the low rate of surgical complications in spite of the higher incidence of obstetrical problems in case of medical therapy alone.

Sleep disorders in Parkinson's disease.

The nature of sleep is one of the major sources of dissatisfaction with the quality of life among patients with Parkinson's disease (PD). Difficult sleep maintenance (light and fragmented sleep) and difficulties with sleep initiation are the earliest and most frequent sleep disorders observed in these patients. Sleep disorders are also common in the normal elderly population, suggesting that normal aging may play a role in the etiology of sleep disorders in PD. Factor et al. examined the frequency of various sleep disorders in PD and compared them to those of normal elderly subjects. Sleep fragmentation and spontaneous daytime dozing occurred much more frequently in PD patients than in controls. Sleep fragmentation in PD may be due to an increased skeletal muscle activity, disturbed breathing and REM/non-REM variations of the dopaminergic receptor sensitivity. In parkinsonian patients who developed motor fluctuations (on-off phenomenon, wearing-off) during the day, other common sleep-related motor complaints including nocturnal akinesia, dystonia and painful cramps are observed. In a double-blind cross-over study, we compared the efficacy of a single dose of a chronic release formulation of levodopa/carbidopa (Sinemet CR) with that of a placebo in improving sleep-related motor disturbances in a group of 40 fluctuating PD patients. Sinemet CR significantly improved nocturnal akinesia and increased the hours of sleep in this group of patients. Initiation and maintenance of sleep are problems that may not be solved with antiparkinsonian treatment.

Determination of apomorphine in human plasma by alumina extraction and high-performance liquid chromatography with electrochemical detection.

Apomorphine is a powerful agonist of dopaminergic receptors which several years ago was introduced into the therapy of Parkinson's Disease. The pharmacological activity of apomorphine already appears significant at low doses. Unfortunately, the difficulty in determining the drug in plasma at low concentrations hampers the completion of accurate pharmacokinetic studies in humans. Considering the analogy of apomorphine with the molecular structure of catecholamines, the extraction of the drug from plasma was optimized by using adsorption on alumina, a technique widely used for noradrenaline and adrenaline analysis in clinical chemistry laboratories. This method proved particularly efficient and selective in apomorphine extraction from plasma prior to high-performance liquid chromatographic analysis. After pretreatment of 200 microliters of plasma sample with 40 mg of alumina and 10 microliters of tris buffer (pH 8.6), the drug was eluted with 200 microliters of an acidic-organic solution. One volume of the supernatant was mixed with two volumes of phosphate buffer (pH 3.6), and 100 microliters of the obtained mixture were injected into the HPLC system. The chromatograph was equipped with a C18 reversed-phase column and with an electrochemical coulometric detector fitted with a high-sensitivity cell (first electrode 0.00 volts, second electrode +0.35 volts). Sensitivity (20 pg of injected drug), precision (CV within assay and between assays of 3.7% and 5.6%, respectively) and accuracy were comparable to more complex analytical procedures. The miniaturisation of the entire sample pretreatment proved very advantageous for pharmacokinetics studies and, in principle, for therapeutic drug monitoring and toxicological investigations.

The long-duration action of levodopa may be due to a postsynaptic effect.

A single dose of levodopa (L-DOPA) reduces motor disability in Parkinson's disease (PD) for a few hours, a short-duration effect. However, there are suggestions that L-DOPA may also produce a long-duration benefit of some days. In the present study, we examined the long-duration action of L-DOPA by observing the time taken to achieve maximum stable benefit after starting a constant dose of sinemet-CR (sinemet-CR) (200 g L-DOPA/50 mg carbidopa) twice daily in nine newly diagnosed patients, and the time taken to deteriorate back to baseline after stopping treatment. A single dose of sinemet-CR (200 mg L-DOPA/50 mg carbidopa) had little obvious short-duration action on the Unified PD Rating Scale (UPDRS) motor scores in the majority of patients, either before starting chronic sinemet-CR therapy (200 mg L-DOPA/50 mg carbidopa, b.i.d.) or after chronic treatment. However, all patients gradually improved on chronic sinemet-CR therapy, taking 9.3 +/- 1.8 days to achieve maximum response. On stopping chronic sinemet-CR treatment, it took 6.8 +/- 3.0 days for the same patients to deteriorate back to baseline motor disability. In similar experiments, the time taken to deteriorate back to baseline after stopping treatment with the directly acting dopamine agonist ropinirole (9-21 mg daily) in eight other de novo patients with PD was found to be 6.2 +/- 1.7 days. The long-duration effect of L-DOPA and ropinirole may, therefore, be due to some slowly evolving postsynaptic pharmacodynamic change in the central nervous system (CNS). Loss of this long-duration action may be responsible for the emergence of motor fluctuations on chronic L-DOPA therapy.

Melperone in the treatment of iatrogenic psychosis in Parkinson's disease.

The pharmacological management of Parkinson's disease (PD) can be complicated by psychiatric disorders induced by antiparkinsonian drugs. The reduction or withdrawal of levodopa (l-dopa) and other drugs commonly used in the treatment of PD may attenuate the psychosis but exacerbate motor impairment and disability. Melperone is an atypical antipsychotic drug showing in vivo a greater relative affinity for the 5-HT2 than the D2 receptors. A two-year study to assess the clinical efficacy and the safety of melperone in the management of iatrogenic psychosis in 30 parkinsonian patients was carried out. Neurological evaluation was performed with patients in the "off" and in the "on" state using the motor examination of the Unified Parkinson's Disease Rating Scale (UPDRS). Time spent in "on" state was evaluated using the self-evaluation diary of daily life. To assess psychiatric disturbances the modified version of the Brief Psychiatric Rating Scale (BPRS) was used. The mean BPRS score was significantly reduced when comparing baseline with individual examinations; no statistically significant differences were found between subsequent examinations. UPDRS motor score and time spent in "on" state during daily life showed no statistically significant differences when comparing baseline with subsequent examinations. Two patients dropped out because of excessive sedation problems but in the remaining 28 patients melperone proved to be optimally tolerated.

Fluctuating parkinsonism: a pilot study of single afternoon dose of levodopa methyl ester.

Thirty-four patients with idiopathic fluctuating Parkinson's disease and early afternoon "delayed on" or severely resistant "off" periods, in spite of long-term antiparkinsonian therapy, were studied. The first afternoon levodopa administration was substituted with an equimolar dosage of the liquid formulation levodopa methyl ester (LDME). The major end-points for efficacy were latency to "on" and duration of "on" periods. The patients were divided into five subgroups according to their baseline treatment and they were evaluated monthly for 6 months using the Unified Parkinson's Disease Rating Scale. The patients completed weekly self-evaluation using an "on-off" chart. LDME was well tolerated by all the patients. A statistically significant reduction in latency to "on" was observed in all patients. The clinical effect of LDME remained stable during the treatment period (repeat measures ANOVA). The more rapid clinical effect of LDME and its stable and predictable antiparkinsonian activity represents a new and useful approach for treating patients with complicated Parkinson's disease.

The clinical efficacy of a single afternoon dose of levodopa methyl ester: a double-blind cross-over study versus placebo.

Levodopa methyl ester (LDME) is a highly water soluble derivative produced by esterification of the carboxilic acid moiety of the L-Dopa molecule that is rapidly hydrolyzed to L-Dopa and can be administered orally in an easily dosable liquid form. In this study the relative efficacy and tolerability of a single dose of an oral solution of 250 mg of LDME was compared to that of placebo in reversing afternoon off period. A controlled double-blind cross-over study versus placebo had previously been carried out in 25 idiopathic parkinsonian patients with predictable fluctuations in motor performances. The study design stipulated the sequential administration of LDME and placebo in group A and placebo and LDME in group B on two consecutive days. All patients turned "on" with LDME and none with placebo solution. The mean latency to "on" was 25.3 +/- 13.5 min for the A group and 27.6 +/- 3.9 min for group B (Fig. 2) and the "on" duration was 147.7 +/- 50.3 min and 163.3 +/- 39.3 min for the A and B groups respectively. Five patients suffering from drug resistant "off" phenomena turned "on" with LDME solution showing a mean latency to "on" of 31.4 +/- 6.2 min.

Attraction of Chironomus salinarius (Diptera: Chironomidae) to artificial light on an island in the saltwater lagoon of Venice, Italy.

The attraction of adult Chironomus salinarius to incandescent 3-W lamps of 7 different colors used in CDC traps was studied on a small island in the lagoon of Venice, Italy. An ANOVA indicated that the lamp type was a highly significant (P < 0.01) factor associated with differences in light trap catch (28% of total variation), as well as catch per lux (18% of total variation). The white lamp attracted higher numbers of adults than the other 6 color lamps. Yellow was the second most preferred, and red was the least attractive. There was a strong linear relationship (r = 0.93) between the catch and light intensity, which suggested that intensity was the primary factor influencing catch. However, catch per unit brightness (lux) tended to be inversely proportional to the peak wavelength associated with the lamp color (e.g., the violet lamp had the highest catch/lux, and the red lamp had the lowest). The corresponding regression model, Catch = 49 + [(48,013/lambda) - 63] . L, in which the slope associated with light intensity in lux (L) is inversely proportional to the peak wavelength in nm (lambda) explained 97% of the variation among lamp catch means. Manipulating light intensity and color could be useful to divert adult C. salinarius populations from midge-affected areas for control purposes.

Color VEPs in Parkinson's disease.

Evoked potential studies have confirmed visual pathway impairment in Parkinson's disease. Dopamine is also known to be involved in retinal color vision mechanisms. In this study, pattern evoked potentials were recorded in 20 parkinsonian patients in "on" and "off" conditions to compare the sensitivity of black-and-white and color pattern stimuli. Evoked responses to colored patterns proved more sensitive to L-DOPA therapy. This finding supports the proposed dopamine modulation of the retinal color system and suggests that color pattern evoked potential studies might be used in monitoring dopamine therapy in parkinsonian patients.

Comparison between a fast and a slow release preparation of levodopa and a combination of the two: a clinical and pharmacokinetic study.

After overnight drug withdrawal and in the fasting state, 11 patients with Parkinson's disease (PD) and a fluctuating response to chronic levodopa treatment were given, in random sequence on consecutive days, equivalent levodopa doses (with peripheral decarboxylase inhibitor) (a) as levodopa methyl ester (ME), (b) as Sinemet CR, or (c) as half the dose of ME together with a halved tablet of Sinemet CR. All patients turned ON rapidly after treatments a and c, but only half did so after treatment b. On period duration was longest after treatment c, intermediate after treatment a, and shortest after treatment b. Pharmacokinetic analysis in a subset of 6 patients revealed no significant difference between treatments a and c, although there was a trend for t1/2 to be longer after treatment c. We conclude that giving ME with a halved tablet of Sinemet CR provided a useful clinical balance between rapid onset and extended duration of action of at least the first levodopa intake of the day. In view of differing release profiles between whole and halved tablets of Sinemet CR, similar single-dose pharmacokinetic studies, followed by sequential-dose clinical studies, are indicated when Sinemet CR 125 tablets soon become available.