Evaluation of high-resolution X-ray absorption and emission spectroscopy for the chemical speciation of binary titanium compounds.

For the chemical speciation of binary compounds of tri- and tetravalent titanium, high-resolution X-ray absorption and emission spectra were recorded in different energy regimes in order to evaluate and to qualify both near-edge X-ray absorption fine structure (NEXAFS or XANES) spectroscopy and wavelength-dispersive X-ray emission spectroscopy (WDXES) as spectroscopic methods for this analytical task. A high resolving power in the excitation channel was ensured by use of monochromatic synchrotron radiation provided by BESSY II, where the soft X-ray emission spectra were recorded as well. In the hard X-ray range, emission measurements were performed at SPring-8. For a comparison of the information gained from the various methods, the titanium compounds were classified according to the bonded titanium's oxidation state. Thus, it was possible to distinguish between inner atomic effects due to different oxidation states and external effects related to the respective ligand and the surrounding structure. It becomes evident, that certain compounds, while hardly distinguishable in their Ti-K XANES spectra, still show significant differences in their emission characteristics. On the other hand, some compounds with little difference in their emission spectra are easily distinguished by their NEXAFS structures. Only the combined use of the complementary methods both in the soft and the hard X-ray range allows for a reliable speciation of tri- and tetravalent titanium compounds.

Development and evaluation of the Parkinson Psychosis Questionnaire A screening-instrument for the early diagnosis of drug-induced psychosis in Parkinson's disease.

OBJECTIVE: Drug-induced psychosis is a frequent side-effect in the treatment of advanced Parkinson's disease (PD). We sought to develop and evaluate a brief instrument for early recognition of drug-induced psychosis in PD. METHODS: We developed the "Parkinson Psychosis Questionnaire" (PPQ), which consists of screening questions for typical early signs and psychotic symptoms in PD and which quantifies the frequency and severity of four clinical categories-sleep disturbances, hallucinations/illusions, delusions and orientation. We performed an internal validation of the PPQ in 50 unselected patients with parkinsonism. The Brief Psychiatric Rating Scale (BPRS) and the "Structurized Clinical Interview" (SCID) for DSM IV were applied to the same patients as external references. RESULTS: Of 50 subjects, 49 suffered from idiopathic PD and one from probable MSA-P. Hoehn and Yahr stages in "on" ranged from 1.5 to 4. Sensitivity of the PPQ test for drug-induced psychosis according to SCID was 100 % (95 % CI: 73.5%, 100%); while specificity was 92.1 % (95% CI: 78.6%, 98.3 %). The PPQ severity score was highly correlated with BPRS. We derived a linear prediction formula, which transformed PPQ into BPRS scores. CONCLUSION: The PPQ appears to be a suitable, and easily administered instrument for early diagnosis of drug induced psychosis in routine PD care. Whether the PPQ could also be a valuable tool for monitoring follow-up studies and therapeutic intervention trials remains to be tested.

Experiences with Sinemet CR in the Paracelsus-Elena-Klinik.

In an open-label study, 20 patients with peak-dose dyskinesia and/or end-of-dose fluctuations were switched from standard Sinemet to Sinemet CR. Seventeen patients showed good tolerance and therapeutic results for at least 6 months. However, 10 patients showed a slight decrease of this improvement after 6 months; 3 had to be put back on standard Sinemet because of hallucinations (1) or accentuation of dyskinesia and akinesia (2). For optimal results, a higher dosage is needed (mean = 33%), but the number of doses per day can be reduced (mean = 30%).

Possible environmental, occupational, and other etiologic factors for Parkinson's disease: a case-control study in Germany.

In a case-control study, we investigated the possible etiologic relevance to Parkinson's disease (PD) of rural factors such as farming activity, pesticide exposures, well-water drinking, and animal contacts; toxicologic exposures such as wood preservatives, heavy metals, and solvents; general anesthesia; head trauma; and differences in the intrauterine environment. We recruited 380 patients in nine German clinics, 379 neighborhood control subjects, and 376 regional control subjects in the largest case-control study investigating such factors and collected data in structured personal interviews using conditional logistic regression to control for educational status and cigarette smoking. The latter was strongly inversely associated with PD. There were significantly elevated odds ratios (OR) for pesticide use, in particular, for organochlorines and alkylated phosphates, but no association was present between PD and other rural factors. A significantly elevated OR was present for exposure to wood preservatives. Subjective assessment by the probands indicated that exposure to some heavy metals, solvents, exhaust fumes, and carbon monoxide was significantly more frequent among patients than control subjects, but this was not confirmed by a parallel assessment of job histories according to a job exposure matrix. Patients had undergone general anesthesia and suffered severe head trauma more often than control subjects, but a dose-response gradient was not present. Patients reported a significantly larger number of amalgam-filled teeth before their illness than control subjects. The frequency of premature births and birth order did not differ between patients and control subjects. Patients reported significantly more relatives affected with PD than control subjects. These results support a role for environmental and genetic factors in the etiology of PD.

Diet and Parkinson's disease. I: A possible role for the past intake of specific foods and food groups. Results from a self-administered food-frequency questionnaire in a case-control study.

In a case-control study, we compared the past dietary habits of 342 Parkinson's disease (PD) patients recruited from nine German clinics with those of 342 controls from the same neighborhood or region. Data were gathered with a structured interview and a self-administered food-frequency questionnaire, and analyzed using multivariate conditional logistic regression to control for educational status and cigarette smoking. There was no significant difference between cases and controls in the consumption of fruits and vegetables, although there was a negative trend for the consumption of raw vegetables. Controls reported a higher potato consumption than patients (OR = 0.43, 95% confidence interval [CI]: 0.24-0.74, highest versus lowest quartile). Patients reported eating significantly larger quantities of sweet foods as well as having more snacks than controls. This may, however, be the result of an illness-related change in dietary habits leading to a selective recall effect, since sweet foods may enhance the transport of L-dopa across the blood-brain barrier. We also found that patients consumed less beer (OR = 0.26, 95% CI: 0.14-0.49) and spirits (OR = 0.56, 95% CI: 0.36-0.86), but not wine, and they consumed less coffee (OR = 0.27, 95% CI: 0.14-0.52, highest versus lowest quartile), but not tea, than controls. This may relate to a possible interaction between dopaminergic activity and the intake of ethanol or caffeine. Significantly more patients than controls reported ever consuming raw meat (OR = 1.78, 95% CI: 1.21-2.63). These results suggest that the intake of certain foods may be associated with the development of PD.

Diet and Parkinson's disease. II: A possible role for the past intake of specific nutrients. Results from a self-administered food-frequency questionnaire in a case-control study.

In a case-control study, we compared the past dietary habits of 342 Parkinson's disease (PD) patients recruited from nine German clinics with those of 342 controls from the same neighborhood or region. Data were gathered with a structured interview and a self-administered food-frequency questionnaire. Nutrient intakes were calculated from the reported food intakes through linkage with the German Federal Food Code and analyzed using multivariate conditional logistic regression to control for total energy intake, educational status, and cigarette smoking. At the macronutrient level, patients reported higher carbohydrate intake than controls after adjustment for total energy intake, smoking, and educational status (OR = 2.74, 95% confidence interval [CI]: 1.30-6.07, for the highest versus lowest quartile, p trend = 0.02). This was reflected in higher monosaccharide and disaccharide intakes at the nutrient level. There was no difference between patients and controls in protein and fat intake after adjustment for energy intake. We found an inverse association between the intakes of beta-carotene (OR = 0.67, 95% CI: 0.37-1.19, p trend = 0.06) and ascorbic acid (OR = 0.60, 95% CI: 0.33-1.09, p trend = 0.04) by patients, although only the trend for ascorbic acid intake reached statistical significance. There was no difference between groups for alpha-tocopherol intake after adjustment for energy intake. We also found that patients reported a significantly lower intake of niacin than controls (OR = 0.15, 95% CI: 0.07-0.33, p trend < 0.00005). Our results suggest that if antioxidants play a protective role in this disease, the amounts provided by diet alone are insufficient. Although the interpretation of the inverse association between niacin intake and PD is complicated by the high niacin content in coffee and alcoholic beverages, which were also inversely associated with PD in this study, the strength of this association and its biologic plausibility warrant further investigation.

Remote memory in Parkinson's disease and senile dementia.

Remote memory for public events was investigated in 14 demented patients with Parkinson's disease (PD), 14 non-demented PD patients, and 14 controls. These groups were compared with 16 demented patients with dementia that was due to Alzheimer or was of vascular origin (SDAVT), and with a group of elderly controls. The two demented groups were of a different age but displayed a comparable degree of dementia. Remote memory was assessed using a 'famous events' questionnaire with items both of comparable salience and difficulty. Results showed severely impaired retrograde memory functions in the two demented groups for both recall and recognition with non-demented PD patients performing similar to the controls. Remote memory impairments extended 30-40 years without any temporal graded memory losses. Non-demented PD patients and controls showed an inferior free recall performance, especially for the remote past. The two PD groups benefited from recognition to the same extent as the controls, whereas the improvement for SDAVT patients was inferior when compared to their elderly controls. In contrast to SDAVT patients, anterograde memory was associated with remote memory for specific decades in demented PD patients. The results are interpreted with respect to an underlying retrieval deficit with a superimposed anterograde impairment common to both types of dementia and an additional loss of storage sites in SDAVT patients.

Smoking and Parkinson's disease: a case-control study in Germany.

BACKGROUND: In a hospital based case-control study, we investigated the role of environmental factors in the aetiology of Parkinson's disease. This paper describes our results on smoking habits. METHODS: The smoking histories of 380 Parkinson's disease (PD) patients recruited from nine German clinics were compared to those of age- and sex-matched control subjects (379 neighbourhood controls and 376 controls from the same region). Detailed information on smoking behaviour was collected in structured personal interviews in order to calculate the number of pack-years smoked up to the time of diagnosis. Conditional logistic regression was used to calculate odds ratios (OR) and control for potential confounders. RESULTS: Among PD patients, 44% had ever smoked, as compared to 59% in both control groups. Among ever-smoking patients, 74% quit prior to the date of diagnosis, as compared to roughly 45% of the ever-smoking control subjects. The OR for ever having smoked was 0.5 (95% confidence interval [CI]: 0.3-0.7), P trend < 0.00005). CONCLUSIONS: The results are considered in terms of criteria for causality. Plausible explanations for the observed inverse association between smoking and PD include: 1. A genetic predisposition that increases the risk for PD (such as defective detoxification enzymes) simultaneously decreases the likelihood of smoking. 2. Inherently lower dopamine levels in predestined PD patients cause them to be less prone to addiction. 3. Smoking is neuroprotective.

The maximum low-dose RBE of 17.4 and 40 keV monochromatic X rays for the induction of dicentric chromosomes in human peripheral lymphocytes.

Schmid et al. recently reported on the maximum low-dose RBE for mammography X rays (29 kV) for the induction of dicentrics in human lymphocytes. To obtain additional information on the RBE for this radiation quality, experiments with monochromatized synchrotron radiation were performed. Monochromatic 17.4 keV X rays were chosen for comparison with the diagnostic mammography X-ray spectrum to evaluate the spectral influence, while monochromatic 40 keV X rays represent a higher-energy reference radiation, within the experiment. The induction of dicentric chromosomes in human lymphocytes from one blood donor irradiated in vitro with 17.4 keV and 40 keV monochromatic X rays resulted in alpha coefficients of (3.44 +/- 0.87) x 10(-2) Gy(-1) and (2.37 +/- 0.93) x 10(-2) Gy(-1), respectively. These biological effects are only about half of the alpha coefficients reported earlier for exposure of blood from the same donor with the broad energy spectra of 29 kV X rays (mean energy of 17.4 keV) and 60 kV X rays (mean energy of 48 keV). A similar behavior is evident in terms of RBEM. Relative to weakly filtered 220 kV X rays, the RBEM for 17.4 and 40 keV monochromatic X rays is 0.86 +/- 0.23 and 0.59 +/- 0.24, respectively, which is in contrast to the RBEM of 1.64 +/- 0.27 for 29 kV X rays and 1.10 +/- 0.19 for 60 kV X rays. It is evident that the monochromatic radiations are less effective in inducing dicentric chromosomes than broad-spectrum X rays with the corresponding mean energy value. Therefore, it can be assumed that, for these X-ray qualities with broad energy spectra, a large fraction of the effects should be attributed predominantly to photons with energies well below the mean energy.

Workshop IV: drug treatment guidelines for the long-term management of Parkinson's disease.

An attempt was made to establish a decision algorithm for the treatment of idiopathic Parkinson's disease at various stages and in different subgroups such as akinetic-rigid or tremor dominance type. We suggest treating young patients with selegiline and a dopamine agonist. In the tremor dominance type we use either budipine or a dopamine agonist. Due to levodopa-induced dyskinesia, we try to avoid levodopa in the early stages of the disease and use it only later in more advanced situations in a combination therapy with dopamine agonists. Since IPS is not only based upon dopamine deficiency but also on resulting glutamatergic overstimulation, we advocate the use of a glutamate antagonist such as amantadine or budipine. Catechol-O-methyl inhibitors are very helpful when wearing-off occurs. Anticholinergics are only used in the early stages of tremor-dominant IPS because we fear enhancing the risk of dementia.

Deep-brain stimulation for Parkinson's disease.

Deep brain simulation (DBS) is a powerful new therapeutic approach for patients with Parkinson's disease. However, patient selection is critical for a valuable therapeutic result. Dopa sensitivity of the target symptoms, severe disability and low neurosurgical risks are among the major criteria for this indication. Other criteria like age or cognition must still be addressed in future prospective studies. The preferred target for DBS in PD is the subthalamic nucleus for various good reasons. However, prospective studies for this procedure are lacking and some clinical problems may be more easily solved with targeting the internal pallidum or the thalamus. Despite major progress in this field, much work remains to be done.

The current significance of physiotherapeutic measures in the treatment of Parkinson's disease.

Physical measures as adjuvant therapy in Parkinson's disease have so far received insufficient investigation from the viewpoint of either their clinical effectiveness or of their theoretical rationale, although they are widely prescribed in practice and contribute a substantial cost factor to the overall treatment. Most attention has been devoted to movement therapy, which may admittedly only achieve minor improvements in motor performance but contributes substantially to subjective improvement of the well-being of the patients and to the maintenance of their physiological functions. Speech therapy seems to be effective only for patients who are highly motivated and have not suffered any psychological deficits and who continue exercising on their own. Massage, ergonomic treatment approaches and the nowadays fashionable area of various relaxation techniques have received very little attention. Our own trials with vibro-massage (swing-exbusar) for the loosening of muscular rigidity have led to no sustained improvement, and our attempts to improve speech defects in Parkinsonian patients by the application of laser acupuncture have likewise not resulted in improvement.

R-(-)-deprenyl in the treatment of end-of-dose akinesia.

In two trials, we have studied the effectiveness and tolerability of L-deprenyl, a selective MAO B inhibitor, in the treatment of end of dose akinesia in patients with Parkinson's disease. The first trial was designed as an open controlled trial. In the L-deprenyl phase, an improvement in fluctuations in motor function as well as an overall reduction in the sum score of Webster's rating scale from 12.5 to 8.9 was observed, which almost returned to baseline during the placebo phase. The second trial was designed as a randomized trial comparing L-deprenyl therapy with a low-dose bromocriptine regimen. Both therapeutic approaches yielded the same results with respect to fluctuations; the CURS sum score dropped from 37 to 26. As regards tolerability, however, L-deprenyl was superior to bromocriptine.

Partnership and depression in Parkinson's disease.

In this study, the influence of partnership on depression and coping with Parkinson's disease has been investigated. Twenty-three single female patients, 46 married patients (23 female, 23 male) with unimpaired partnership and 42 patients (21 female, 21 male) whose partnership had worsened since the onset of disease, were compared with regard to depression and self reported extent of psychosocial distress. Single female patients tended to have higher depression scores than patients in a stable partnership, especially in items concerning personal worthlessness and senselessness of life. Patients differed in the extent of distress concerning social behavior, psychological problems/anxiety and efficiency. Within the group of single female patients two subgroups emerged: (1) patients with low extent of distress in all aspects; (2) patients who were highly distressed by psychological problems and physical disability but weakly distressed from social interaction. Male and female patients living in a stable partnership reported only a generally low to moderate extent of distress. More than half of the male and female patients who reported an impairment of their relationship also had scores of moderate to severe depression. These patients also had the highest extent of distress in each of the aspects assessed. The results are discussed with regard to possible interactive effects of the disease, quality of the partnership and availability of coping strategies.