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Long-term levodopa treatment in Parkinson's disease is typically associated with "motor side effects" consisting in dyskinesias and/or fluctuations in motility referred to as the on-off phenomena. The main objective of this prospective, randomized, multi-centre study was to determine to what extent the development of such complications could be prevented by partial substitution of levodopa monotherapy (L-DOPA/benserazide) by bromocriptine in patients with early symptoms of the disease. The basic trial population included 674 newly diagnosed Parkinsonian patients that were randomly allocated to monotherapy with levodopa or a combination therapy based upon a nearly 40% replacement of levodopa by bromocriptine. The two target regimens had to be consistently maintained for 42 months. Parkinsonian symptoms were assessed by means of the Webster rating scale, the Hoehn and Yahr scale, and the Zung Self-Rating Depression scale. Motor side effects and adverse events were recorded at each regular clinic visit. Neurological symptoms improved and stabilized in a similar manner during treatment with both regimens throughout the study period. Motor side effects were observed in more patients on levodopa alone than on combination therapy (28.8 vs 20%; p = 0.008). According to Kaplan-Meier estimates the cumulative probability of experiencing motor side effects was 0.43 on monotherapy, compared to 0.28 on combination therapy, which was equal to a one third reduction of risk (p = 0.025). In regard to motor side effects, the degree of substitution of levodopa proved relevant: patients with> 50% substitution by bromocriptine exhibited half the risk observed in those with < 30% (p = 0.045). The overall burden of motor side effects, as reflected by a sum score based upon the relevance, the severity and the extent of motor dysfunction, was also significantly less on combination therapy (p = 0.046). In conclusion, partial substitution of levodopa by bromocriptine (> 30%) as first-line treatment of Parkinson's disease proves active in the prophylaxis of levodopa associated motor side effects. Early combination therapy therefore extends the period of optimal disease control.

L-Dopa supplemented by a peripheral decarboxylase inhibitor is considered the most potent therapeutic regimen prolonging active life in Parkinsonian patients. The long-term benefit of therapy is limited by adverse effects, such as dyskinesia and on-off phenomena, which can be mitigated by the concomitant administration of dopamine agonists, such as bromocriptine. In order to quantify the beneficial impact of early combination therapy, a controlled clinical trial (PRADO: PRA videl1 + DO pa) in patients with early Parkinson's disease was carried out, whereby L-Dopa monotherapy (in a fixed combination with benserazide (DoBe) was being compared with the same combination plus bromocriptine (DoBeBro). Patients were recruited and treated by 101 practising neurologists in the Federal Republic of Germany and in Hungary. Twenty seven clinical university centers cross-checked the patients at regular intervals. The trial started with 3 months of DoBe monotherapy (median dose of 375 mg L-Dopa for both randomized groups) followed by gradual substitution of DoBe by bromocriptine over 3 months in one of the groups (250 mg L-Dopa/10 mg bromocriptine). The target medication was maintained from study months 6 to 54. Parkinsonian symptoms were classified according to the Webster rating scale, the Hoehn and Yahr scale and the Zung Self-Rating Depression Scale. Adverse events and life status were checked at regular intervals. Special emphasis was given to motor performance tests. 587 patients (302 in the DoBe group and 285 in the DoBeBro group) were available for intention-to-treat analysis. Both groups were homogeneous at baseline in all observed parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Data from 14 independent controlled clinical trials on the oral behavior of Classes 1 and 2 amalgam restorations, with a follow-up between five and 15 years, were re-evaluated by secondary analysis for the influence of alloy composition on the survival of amalgam restorations. For the analysis, 3119 restorations were available, which were made from 24 different alloys by a group of seven operators. The alloys were divided into four groups according to their zinc content (zinc-containing and zinc-free) and their copper content (conventional and high-copper). During the follow-up of the trials, the restorations were annually assessed for failures, which were classified as to (1) restoration-, (2) restorative process-, and (3) patient-related reasons. With the restoration-related failures, survival functions of the restorations were estimated by alloy and alloy group. The total number of failed restorations was 481, of which 77% were restoration-related and 14% process-related. Eighty percent of the restoration-related failures were due to some form of fracture of the amalgam. Restorations of conventional zinc-free alloys had the shortest survival. After 13 years, only 25% survived. Zinc and a high copper content had an equally favorable influence on the survival rate, which was 70% after 13 years when either was present. The highest survival rates were of restorations of zinc-containing high-copper alloys: 85% after 13 years. The zinc and copper contents of the alloy contributed to the corrosion resistance of the amalgams, which in turn influenced the survival of the restoration. The current ISO Standard 1559 on alloys for dental amalgam should be modified to account for these factors that influence the survival of amalgam restorations.

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