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Background: The Evaluate Patient OutComes (EPOC) study assessed physician- and patient-reported outcomes in individuals with relapsing multiple sclerosis who switched directly from injectable disease-modifying therapy (iDMT; glatiramer acetate, intramuscular or subcutaneous interferon beta-1a, or interferon beta-1b) to once-daily, oral fingolimod. Post hoc analyses evaluated the impact of a switch to fingolimod versus staying on each of the four individual iDMTs., Methods: Overall, 1053 patients were randomized 3:1 to switch to fingolimod or remain on iDMT. The primary endpoint was the change in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction score. Secondary endpoints included changes in scores for TSQM Effectiveness, Side Effects and Convenience subscales, Beck Depression Inventory-II (BDI-II), Fatigue Severity Scale (FSS), Patient-Reported Outcome Indices for Multiple Sclerosis (PRIMUS) Activities, 36-item Short-Form Health Survey (SF-36) Mental Component Summary (MCS) and Physical Component Summary (PCS) and mean investigator-reported Clinical Global Impressions of Improvement (CGI-I). All outcomes were evaluated after 6 months of treatment., Results: Changes in TSQM Global Satisfaction scores were superior after a switch to fingolimod when compared with scores in patients remaining on any of the iDMTs (all p <0.001). Likewise, all TSQM subscale scores improved following a switch to fingolimod (all p <0.001), except when compared with glatiramer acetate for the TSQM Side Effects subscale (p = 0.111). FSS scores were found to be superior for fingolimod versus remaining on subcutaneous interferon beta-1a and interferon beta-1b, BDI-II scores were significantly improved for fingolimod except for the comparison with intramuscular interferon beta-1a, and SF-36 scores were superior with fingolimod compared with remaining on interferon beta-1b (MCS and PCS; p = 0.030 and p = 0.022, respectively) and subcutaneous interferon beta-1a (PCS only; p = 0.024). Mean CGI-I scores were superior with fingolimod when compared with continuing treatment with any of the iDMTs (all p <0.001)., Conclusions: After 6 months, a switch to fingolimod showed superiority compared with remaining on each iDMT for a range of patient- and physician-reported outcomes, including global satisfaction with treatment., Trial Registration: ClinicalTrials.gov NCT01216072 .

Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by morphologic alterations involving efferent cerebral vascular paths. CCSVI has been implicated as a contributing factor to multiple sclerosis (MS) but this theory is highly controversial. We report 3 cases of CCSVI patients with MS who had undergone internal jugular veins (IJVs) angioplasty to restore vessels patency. All patients reported significant symptomatic improvement after angioplasty until symptoms recurred after restenosis of the treated IJVs. Surgical IJVs reconstruction was performed. Patients' symptoms gradually improved and the benefits were maintained at the 1-year follow-up., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: In pivotal phase 3 studies, fingolimod treatment initiation was associated with a transient reduction in heart rate (HR). Atrioventricular (AV) conduction delays, which were typically asymptomatic, were detected in a small minority of patients., Objective: We report the first-dose effects of fingolimod in patients who switched from injectable therapies during the Evaluate Patient OutComes (EPOC) study (ClinicalTrials.gov Identifier: NCT01216072)., Methods: This was a phase 4, 6-month, randomized, active-comparator, open-label, multicenter study. It included over 900 fingolimod-treated patients with relapsing multiple sclerosis, with subgroups of individuals who were receiving common concomitant HR-lowering medications or had pre-existing cardiac conditions (PCCs). Vital signs were recorded hourly for 6h post-dose. A 12-lead electrocardiogram was obtained at baseline and at 6h post-dose., Results: A transient decrease in mean HR and blood pressure occurred within 6h of the first fingolimod dose. The incidence of symptomatic bradycardia was low (1%); eight patients reported dizziness and there was one case each of fatigue, palpitations, dyspnea, cardiac discomfort, and gait disturbance. These symptomatic events were typically mild or moderate in severity and all resolved spontaneously, without intervention or fingolimod discontinuation., Conclusion: First-dose effects in patients with PCCs and in those receiving concomitant HR-lowering medications were consistent with effects observed in the overall study population and with results from previous clinical trials. The EPOC study provides additional data demonstrating the transient and generally benign nature of fingolimod first-dose effects on HR and AV conduction in a large population that is more representative of patients encountered in routine clinical practice than in the pivotal trials., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The Evaluate Patient OutComes (ClinicalTrials.gov Identifier: NCT01216072) study was conducted in North America to assess patient- and physician-reported treatment satisfaction in patients with relapsing multiple sclerosis (MS) who received oral fingolimod for 6 months after switching from an injectable disease-modifying therapy (iDMT), without an intervening washout., Methods: In this open-label, multicenter study, patients were randomized 3:1 to once-daily fingolimod 0.5mg or iDMT. The primary study objective was to evaluate differences in satisfaction measured using the Treatment Satisfaction Questionnaire for Medication v1.4., Results: Of 1053 patients randomized, 790 patients received fingolimod and 263 patients received iDMT. Treatment satisfaction improved significantly in patients who switched to fingolimod compared with those who continued iDMT. Patients also reported significant improvements in health-related quality of life, reduced depression, and reduced fatigue severity after a switch to fingolimod. No difference between the treatment groups was detected on the Patient Reported Indices for MS Activities scale. The safety profile of fingolimod was consistent with that reported in the pivotal phase 3 studies. The most commonly reported adverse events were more prevalent in patients who switched to fingolimod than in those who continued iDMT (headache: 12% vs 3%; fatigue: 12% vs 6%). No significant relationship between lymphocyte counts and infection rates was observed and there was no evidence of additive immune-system effects, which might be expected when switching to a different class of immunomodulatory therapy with no intervening washout., Conclusion: Patients who switched from iDMT to fingolimod had significant improvements in most self-reported outcomes compared with those who continued iDMT., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) present in the urine are mainly released from cells of the nephron and can therefore provide information on kidney function. We here evaluated the presence of vesicles expressing the progenitor marker CD133 in the urine of normal subjects and of patients undergoing renal transplant. We found that EV expressing CD133 were present in the urine of normal subjects, but not of patients with end stage renal disease. The first day after transplant, urinary CD133+ EVs were present at low levels, to increase thereafter (at day 7). Urinary CD133(+) EVs significantly increased in patients with slow graft function in respect to those with early graft function. In patients with a severe pre-transplant vascular damage of the graft, CD133(+) EVs did not increase at day 7. At variance, the levels of EVs expressing the renal exosomal marker CD24 did not vary in the urine of patients with end stage renal disease or in transplanted patients in respect to controls. Sorted CD133(+) EVs were found to express glomerular and proximal tubular markers. These data indicate that urinary CD133(+) EVs are continuously released during the homeostatic turnover of the nephron and may provide information on its function or regenerative potential.

Background: The chemical, physical, and morphologic characteristics of the implant surface play a fundamental role during the osteointegration process. Implant design is of paramount importance in determining implant primary stability and implant ability to sustain loading during and after osteointegration. LASER treatment of the surface allows defining the precise parameters of roughness to obtain a regular and repeatable surface in total absence of contamination., Purpose: The aim of this study was to analyze the behavior of implant stability of LASER-treated surface implants by repeated resonance frequency analysis (RFA) measurements during 2 years in patients with complete upper maxilla edentulism subject to an immediate-loading protocol., Methods: Ten patients were included, and each treated with the insertion of 6 or 8 LASER surface implants according to the individual surgical-prosthetic planning. During the bone drilling and implant insertion, torque values were monitored with a specific handpiece and software. All implants were loaded within 24 hours from the insertion with the application of a temporary full-arch prosthesis. Subsequent follow-up has been done at 24 months from the loading with radiographic controls (OPT) and RFA measurement on all implants at time of implant insertion and at 1, 3, 6, 12, and 24 months from loading., Results: Resonance frequency analyses at 3 and 6 months from the implant loading have shown a rapid increment of implant stability quotient (ISQ) values in the first phases of bone remodeling, subsequent to the peri-implant bone remodeling. The paired comparisons between mean ISQ values by patient showed a statistically significant decrease in primary stability from baseline up to 1 month (P = 0.0039). Subsequent measurements revealed a statistically significant increase in implant stability from 1 up to 3 months (P = 0.0156), from 3 up to 6 months (P = 0.0020), from 6 up to 12 months (P = 0.020), and 12 up to 24 months (P = 0.0391)., Conclusions: Resonance frequency analysis of the LASER-treated surface implants showed good ISQ values at all time point measurements. These results are consistent with data from literature on the analysis of RFA in protocols of immediate loading at the upper maxilla.

Osteoporosis is a systemic disease in which the skeletal condition is characterized by a decreased mass of normally mineralized bone, due to an augmentation of bone resorption processes. Bone biomarkers serum are used for the diagnosis. On the other hand the main cause of the resorption in the bone jaws are periodontitis, inflammatory cysts, developmental cysts, odontogenic neoplasms. Periodontal diseases can be localized to a single site of the jaws or can affect all the teeth, with a massive bone resorption. The cysts are classified in developmental and inflammatory. They caused a local bone resorption in the jaws. Keratocystic odontogenic tumor produces a large bone resorption for its local aggressive nature. Their diagnosis is clinical and radiological.The aim of our review is to find a correlation between bone biomarkers serum and periodontitis, inflammatory cists, developmental cysts, odontogenetic neoplasms.The RANK/RANKL/OPG system is the most studied not only in osteoporosis but also in the periodontitis, inflammatory cysts, developmental cysts, odontogenic neoplasms. In the last years osteoimmunology was used to study the periodontal disease progression, because the immunity cells start the bone resorption processes.A lot of studies analyze the biomarkers present in the biofluids, as saliva and gingival crevicular fluid, but not the correlation with serum biomarkers.Future studies must be organized to deepen the correlation between bone biomarkers and bone jaws resorption and to allow diagnosis and prognosis of periodontitis, inflammatory cysts, developmental cysts, odontogenic neoplasms.

Two transplant candidates sensitized during pregnancy by a B*44:02 mismatch showed antibodies that reacted with an epitope defined by the 145R+82LR eplet pair shared by all Bw4 antigens in single allele Luminex panels except B13. Both eplets are on one or more alleles of the antibody producer and according to HLAMatchmaker, they are considered intralocus and interlocus matches which should not induce antibodies. The recently developed nonself-self paradigm for HLA epitope immunogenicity has offered a ready explanation why the pair of self-145R and self-82LR eplets on B*44:02 induced specific antibodies. This finding is consistent with the concept that alloantibody responses originate from B-cells with self-HLA immunoglobulin receptors., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The edentulism of the jaws and the periodontal disease represent conditions that frequently leads to disruption of the alveolar bone. The loss of the tooth and of its bone of support lead to the creation of crestal defects or situation of maxillary atrophy. The restoration of a functional condition involves the use of endosseous implants who require adequate bone volume, to deal with the masticatory load. In such situations the bone need to be regenerated, taking advantage of the biological principles of osteogenesis, osteoinduction and osteoconduction. Several techniques combine these principles with different results, due to the condition of the bone base on which we operate changes, the surgical technique that we use, and finally for the bone metabolic conditions of the patient who can be in a state of systemic osteopenia or osteoporosis; these can also affect the result of jaw bone reconstruction.

The effect of B cell cross-match (XM) was investigated in 680 first deceased-donor kidney transplants in a single centre from 1990 to 1999: 74 transplants presented a B-positive XM (Group 1) 606 had a B-negative XM (Group 2). The absence in Group 1 of weak/low-titre anti-HLA Class I antibodies was assured blocking anti-Class I reactivity by treating B cells with non-cytotoxic anti-beta2 microglobulin (alphabeta2 M) serum before XM. Graft survivals up to 5 years were not significantly different; some differences were nevertheless observed: HLA-A,B,DR mismatches influenced graft outcome in Group 1: patients with 0-2 mismatches had better survival than patients with 3-4. When analysed according DR mismatch, patients with 1 mismatch had worse graft survival than well matched patients (p<0.05). No significant difference depending on HLA match was observed in Group 2. Early acute rejection rate was similar in the Groups except the rejection episodes after one year: Group 1 had significantly more. 61/74 patients of Group 1 were retrospectively analysed for anti-HLA-DR,DQ reactivity: only 11/61 had anti-HLA-DR or DQ antibodies (3/11 were donor specific); graft survival and rejections were not significantly different in the patients with and without anti-HLA Class II antibodies. Anti-donor B cell reactivity, at XM, once excluded the presence of weak/low-titre anti-HLA Class I antibodies, did not influence first kidney graft survival.

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.

Glanzmann's thrombasthenia is a congenital hemorrhagic disorder transmitted as an autosomal recessive trait and characterized by altered production and/or assembly of the platelet membrane glycoprotein IIb/IIIa receptor. We describe the perioperative management of a heterozygous carrier of Glanzmann's thrombasthenia submitted to cardiac surgery with cardiopulmonary bypass and the case was complicated by early excessive postoperative bleeding.

Context: The first national quality control (QC) program of histocompatibility serum testing was performed in Italy in 2002., Objective: To monitor the performance of HLA typing laboratories while meeting the accreditation requirements of the European Federation for Immunogenetics (EFI), which require HLA typing laboratories to participate in external QC of their crossmatch and antibody analyses., Design: The Turin Transplant Immunology Service was asked to organize a QC survey of 17 HLA typing laboratories in Italy. Each laboratory received 12 serum specimens and 6 blood samples and was required to perform 36 crossmatches and 12 serum antibody specificity determinations., Settings: Data of participating centers were compared to establish whether EFI requirements were satisfied., Results: In crossmatch analysis, the results of 32 of 36 crossmatches reached the 75% consensus target, with all the participating laboratories meeting the standards of the EFI. In antibody analysis, only 7 of 17 laboratories met the EFI standards., Conclusion: The first Italian QC program shows that the participating laboratories obtained consistent results in crossmatching, whereas the results were less satisfactory in the determination of serum antibody specificity, where consensus was reached only with monospecific sera and antibody-negative samples.

Objective: In many parkinsonian patients with fluctuating disease the early morning levodopa dose is more effective than the following dose on the same day. In this study we investigated whether the poor responsiveness to the early afternoon dose of levodopa depends only on peripheral and central levodopa pharmacokinetics or also on pharmacodynamic factors., Methods: Ten parkinsonian patients experiencing postprandial drug-resistant off periods received two boluses of apomorphine by subcutaneous injection at 8 am and 3 pm on two nonconsecutive days. On day 2, therapy was stopped at 11 am. For each bolus we determined time to on, duration of the on state, magnitude of benefit, and levodopa and apomorphine plasma levels at baseline and immediately after patients reached the on state., Results: The mean duration of on phases was significantly shorter and the apomorphine plasma level needed to reach the on state was significantly higher in the afternoon than in the morning (P<0.01 by paired t test)., Conclusions: This study suggest that there is a change in responsiveness to dopaminergic stimulation during the day. The less effective dopaminergic response in afternoon depends on pharmacodynamic factors and not only on peripheral and central levodopa pharmacokinetic.

The authors investigated the long-duration response to levodopa in advanced Parkinson's disease. Eight patients with advanced Parkinson's disease disabled by severe ON/OFF fluctuations treated by chronic daytime subcutaneous apomorphine infusion with supplemental oral levodopa were studied. On day 1, oral levodopa was withdrawn at 4:00 pm and on the following morning subcutaneous apomorphine infusion was continued at the same rate without levodopa therapy. While receiving apomorphine alone, seven of the eight patients turned ON, and their usual dyskinesias returned. The ON phase persisted for 60 to 100 minutes (mean, 185.7 minutes) but then, despite continued, constant-rate apomorphine infusion to stabilize plasma levels, switched to an OFF phase. The authors conclude that the clinical effect of apomorphine is sustained by levodopa long-duration response. This effect is probably the result of postsynaptic mechanisms. In patients with advanced Parkinson's disease, the long-duration response to levodopa is present although slightly diminished.

Sternomy represents the standard approach to the heart and great vessels in most cardiothoracic procedures. Closure of this incision is simple; however, healing complications such as dehiscence, osteomyelitis, mediastinitis, and superficial wound infection or fistula may occur. We describe an alternative technique for sternal closure using semirigid fixation with thermoreactive clips.

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.

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.

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.

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.

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.

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.

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.

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.

Fluctuations in motor performance are the major problems in chronic management of Parkinson's disease. Most of these fluctuations reflect the decline of levodopa availability. As a consequence, levodopa dosage might be increased and the interdose interval progressively shortened. The postsynaptic dopamine receptors at this point are exposed to a nonphysiologic shift in dopamine level, which may induce changes at the receptor site and contribute to the appearance of "on-off" phenomena and dyskinesias. We compared a group of 18 patients treated for 60 consecutive months with continuous subcutaneous lisuride infusion with a group of 20 patients treated with conventional oral levodopa treatment. The clinical evaluations performed during the study showed in the lisuride group only a worsening of dyskinesias, whereas the other symptoms remained unchanged. In the other group the evaluation scores showed a significant worsening of all long-term treatment complications. The slow-release preparations of levodopa may ensure a more continuous dopaminergic stimulation than standard formulations. However, the use of these compounds is difficult in severely fluctuating patients because the lack of a plasma peak level usually leads to a very long delay before patients turn "on." We studied the pharmacokinetic and clinical effects of the two slow-release preparations of levodopa [Madopar HBS and Sinemet controlled-release (CR)] and a combination of Sinemet CR plus standard Sinemet in 13 fluctuating parkinsonian patients. The results of this study show that the combination of standard Sinemet and Sinemet CR ensures a more prolonged clinical effect with a very short latency to the "on" phase.

Two formulations of the organophosphorus insecticide, temephos (Abathion Granulare, 1% AI granular and Tambro Compresse, 2% AI tablet) were evaluated against Chironomus salinarius midge larvae in 50 x 50 m experimental plots in the saltwater lagoon of Venice, Italy. Each formulation was applied at 0.2 and 0.4 kg AI/ha. Abathion Granulare produced 56 to 73% larval reduction at 0.2 kg AI/ha and 69 to 83% reduction at 0.4 kg AI/ha during 3 wk after treatment. Abathion Granulare lost effectiveness at 4 wk after application at both rates. Posttreatment larval reductions resulting from Tambro Compresse applications ranged from 77 to 86% for 3 wk, and 82 to 92% for 4 wk at rates of 0.2 and 0.4 kg AI/ha, respectively. The tablet formulation (Tambro Compresse) gave better control of C. salinarius (magnitude and duration) than the granular formulation (Abathion Granulare) in these evaluations.

1. A group of 14 fluctuating Parkinsonian patients underwent the subcutaneous Lisuride treatment, administered by an insulin delivery pump. Clinical response has been studied during a one year period. 2. Some patients (8 out of 14) were in combined therapy, assuming a relative small amount of oral L-Dopa together with subcutaneous Lisuride. 3. Lisuride confirmed, also by the subcutaneous route, its antiparkinsonian properties, without any loss of therapeutical efficacy during the 12 month period considered. 4. 7 patients dropped-out from the study, due to psychiatric or systemic side-effects and to "technical" management of the pump. 5. The only 2 patients assuming a 24 hour regimen of Lisuride infusion were among the withdrawn subjects. They were also the only to complain severe psychiatric disturbances.