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Biomedical subjects

R Palm

Publications and source records attributed to R Palm.

At least 19 recordsLinked to original sources
PubMed2006

Selegiline slows the progression of the symptoms of Parkinson disease.

OBJECTIVE: To study the long-term effects of selegiline in monotherapy and in combination with levodopa in the early phase of Parkinson disease (PD). METHODS: One hundred fifty-seven de novo PD patients were randomized in a double-blind, placebo-controlled study of 7 years' duration. In the monotherapy part, selegiline significantly delayed the initiation of levodopa therapy vs placebo. The authors now report the results from the combination part of the study, in which 140 patients received selegiline or placebo in addition to individually tailored levodopa therapy. RESULTS: Compared with placebo, selegiline slowed the progression of disease disability as measured by the Unified Parkinson Disease Rating Scale (UPDRS) total score (p = 0.003) or by motor (p = 0.002) and Activities of Daily Living (p = 0.0002) subscores. After 5 years in combination therapy, the mean difference in the UPDRS total score was nearly 10 points, with patients receiving placebo having 35% higher scores. Simultaneously, patients receiving placebo needed progressively higher doses of levodopa than patients receiving selegiline; after 5 years, the mean dosage of levodopa was 19% higher with placebo than with selegiline (p = 0.0002). Considering the entire (monotherapy and combination therapy) 7-year study time, there was a trend for selegiline to delay the start of wearing-off fluctuations (hazard ratio 0.55, p = 0.08). In both phases of the study, selegiline was safe and well tolerated. CONCLUSIONS: The results of this long-term study confirm earlier findings indicating that selegiline delays the progression of the signs and symptoms of Parkinson disease.

Activities of Daily Living↗
PubMed1998

Selegiline delays the onset of disability in de novo parkinsonian patients. Swedish Parkinson Study Group.

OBJECTIVE: The objective of this study was to investigate the effect of selegiline first as monotherapy and then in combination with levodopa in the early phase of PD. METHODS: A total of 157 de novo PD patients were randomized to receive either selegiline or placebo in a double-blind study until levodopa therapy became necessary. Thereafter, the drugs were withdrawn for an 8-week washout period to evaluate the possible symptomatic effect of selegiline. RESULTS: Analysis of Kaplan-Meier survival curves for each group showed that selegiline delayed significantly the need for levodopa therapy (p = 0.028). The semiannual rate of disability progression was slowed down significantly in the selegiline group analyzed with the Unified Parkinson's Disease Rating Scale (total and motor scores; p < 0.001). Selegiline had a "wash-in" effect (i.e., an initial symptomatic amelioration of PD at 6 weeks and 3 months). However, after the 8-week washout period, no significant differences in the deterioration of disability between the groups was revealed in any of the scales, suggesting that besides having a slight symptomatic effect, selegiline may also have neuroprotective effects. Similarly, the progression of symptoms from baseline to the end of the washout period was significantly slower (p = 0.033) in the selegiline group when the progression was adjusted by the time to reach the end point. Selegiline was well tolerated. CONCLUSIONS: Selegiline delayed significantly the need to start levodopa in early PD. After a 2-month washout period (before the start of levodopa therapy) no significant symptomatic effect of selegiline was seen in comparison with the placebo group, supporting the concept of neuroprotective properties of the drug.

Aged↗
PubMed1996

Flunarizine in stroke treatment (FIST): a double-blind, placebo-controlled trial in Scandinavia and the Netherlands.

INTRODUCTION: An international, multicenter trial was conducted in 331 patients to determine the effect of a large dose of flunarizine (a calcium entry blocker) in the treatment of acute ischemic stroke in the territory of the Middle cerebral artery. METHODS: The administration of the trial medication should start within 24 h after the initial symptoms of stroke. According to a random schedule, the patients were assigned to a 4-weeks double-blind treatment with either flunarizine (n = 166) or placebo (n = 165): one week intravenous administration (50 mg daily), followed by 3 weeks oral treatment (week 2, 21 mg daily; week 3-4, 7 mg daily). All patients had to be investigated by computerized tomography (CT) within 7 days after stroke onset; 36 patients were secundarily excluded because the CT showed another pathology. During the treatment period, other "stroke therapies" were not allowed. Patients were followed up for 24 weeks. RESULTS: After the 24 weeks trial period, the percentage of patients who were dead or pendent (modified Rankin score 3-5) was similar in both treatment groups (flunarizine 67%, placebo 65%). During the trial, the scores for handicap severity (modified Rankin scale), neurological status (Orgogozo) and activities of daily living (modified Barthel index) strongly improved in both treatment groups, but no differences were found between the treatment groups. In this trial, the administration of trial treatment started relatively late after stroke onset (flunarizine group: mean time interval 13.5 h; placebo 12.3 h). A subgroup of patients received trial medication within 6 h after stroke onset (flunarizine n = 31; placebo n = 29). Also in this subgroup, no differences were found between the flunarizine and placebo group. CONCLUSION: Flunarizine did not improve neurologic and functional outcome in patients with acute ischemic stroke.

Activities of Daily Living↗
PubMed1995

Changes in blood manganese levels during pregnancy in iron supplemented and non supplemented women.

Blood manganese levels and iron status indices were determined each trimester in 66 healthy pregnant women. Twenty-five were randomly assigned to iron supplementation, 19 to placebo and 22 received dietary advise aimed at increasing their dietary intake of fibre. Iron supplemented women had significantly higher levels of blood haemoglobin compared to the levels of the two other groups, and higher serum ferritin levels compared to the placebo group. No significant difference in blood manganese levels was observed among the three groups of women. There was a significant increase in blood manganese levels from one trimester to the next, which was slightly more pronounced in non supplemented women. The median values in the three trimesters were 154 (range 79-360) nmol/L, 190 (range 98-408) nmol/L, and 230 (range 133-481) nmol/L, respectively. Pregnancy seems to change manganese status or otherwise influence manganese metabolism irrespective of iron status and iron supplementation.

Adult↗
PubMed1994

The European Stroke Scale.

BACKGROUND AND PURPOSE: For detecting therapeutic effect and matching of treatment groups in stroke trials, a scale that meets the clinimetric criteria is of the utmost importance. METHODS: The European Stroke Scale consists of 14 items selected for their specificity and their prognostic value. It is designed for patients with middle cerebral artery stroke. Interrater reliability, internal consistency, and time for completion were investigated in 74 patients. Intrarater reliability was studied in 38 patients. To establish concurrent validity, two trials were performed in 20 and 44 patients. The scale was correlated with the MCA Neurological Scale, the Canadian Stroke Scale, the Scandinavian Stroke Scale, the Barthel Index, and the Rankin Scale. Correlations were calculated by means of Spearman's correlation coefficient. The trial in 44 patients also investigated the prognostic validity of the scale for 1-month and 8-month neurological, functional, and handicap status. These data were analyzed by linear regression. RESULTS: Interrater (kappa value range, 0.62 to 0.85) and intrarater (kappa value range, 0.65 to 1.00) reliability for each item was good, and internal consistency was excellent (Cronbach's alpha coefficient, 0.92). Mean time for completion was 8.2 minutes (range, 4 to 14 minutes). Correlations of the European Stroke Scale with other neurological scales ranged from 0.93 to 0.95. The correlation with the Barthel Index and the Rankin Scale was 0.84 and -0.86. The R2 values for prognostic validity ranged from 0.45 to 0.81 (P < or = .0001). CONCLUSIONS: The European Stroke Scale has been developed according to the clinimetric criteria.

Adult↗
PubMed1990

Age related changes in weight and the concentrations of zinc and copper in the brain of the adult rat.

Two groups of adult male rats aged 15 weeks and 49 weeks, 15 rats in each group, were analysed for the concentrations of the trace elements zinc (Zn) and copper (Cu) in serum, liver, kidney, and five parts of the brain (cortex, corpus striatum, hippocampus, midbrain + medulla, and cerebellum). All organs increased in weight from 15 weeks to 49 weeks. In all parts of the brain, except for corpus striatum, there was a significant increase of the weights. The dry weight (% of wet) increased in all parts of the brain. In serum, the Zn and Cu concentrations increased from 15 weeks to 49 weeks. In the liver, both concentrations decreased and in the kidney the concentrations increased with increasing age. The Zn concentrations increased in cortex and corpus striatum and decreased in cerebellum and hippocampus. The Cu levels increased in all parts of the brain with the largest changes in corpus striatum. For rats aged 49 weeks, a significant correlation was found between the Cu concentrations of corpus striatum or midbrain + medulla and the fluid consumption. The findings of the present study reveal a dynamic age-related pattern of changes in the concentrations of Zn and Cu in different organs of the adult rat. This stresses the need of age-matching as an important control in experiment studies.

Age Factors↗
PubMed1988

Experimental transmission of enzootic bovine leukosis to sheep: latency period of the tumoral disease.

In the field of viral oncogenesis the latency period is the interval between detectable establishment of infection and appearance of a tumor. Between 1969 and 1985, a total of 60 sheep died with lymphosarcoma. They were inoculated with BLV-positive blood from various donor cows, by various routes, at various ages, etc. A statistical analysis was performed trying to find a correlation between the length of the latency period and, on the other hand, one or more factors, such as sex, family lineage, identity of the dam, age at inoculation, route of inoculation, or origin of the inoculum. None of the above mentioned parameters has a significant effect on the length of the latency period. In two series of sheep inoculated with decreasing number of lymphocytes from BLV-positive donor cows, hematological disorders and tumors appeared at first in recipient animals inoculated with the higher doses of infectious blood. Thus, the inoculated dose has an effect upon the length of the latency period; the higher the dose inoculated, the shorter the latency period. This finding suggests an explanation to the natural occurrence of multiple case herds as opposed to no-tumor case herds. A multiple case herd fulfills two conditions: the presence of a good donor and an efficient route of transmission allowing the transfer to the recipient of the optimal amount of infected blood.

Animals↗
PubMed1986

Effects of long-term phenytoin treatment on brain weight and zinc and copper metabolism in rats.

The effects of phenytoin (PHT) treatment on brain weights and the zinc (Zn) and copper (Cu) concentrations in liver, kidney, and five parts of the brain have been studied in rats. After 32 wk of treatment (daily doses 72-88 mg/kg body weight), significantly reduced brain weights were found in rats sacrificed during treatment, but not in those sacrificed after 14 d of abstinence. The weight reduction mainly seemed to affect cortex, but cerebellum was also influenced. The PHT treatment during 18 wk did not significantly reduce the brain weights. At the end of treatment, significantly increased serum Cu concentrations were found, as well as decreased Zn levels in the liver and low Cu levels in the kidney. No large alterations were found in the trace element concentrations of different brain regions. The PHT treatment for 32 wk induced physical dependence, recorded as convulsions. It is suggested that PHT through a chelate binding with Zn and Cu interferes with the metabolism of the trace elements and the drug may cause a Zn deficiency. The observed decrease of the brain weights may have some parallel to the mental side effects of the drug observed during chronic epilepsy therapy.

Animals↗
PubMed1986

Zinc, total protein, and albumin in CSF of patients with cerebrovascular diseases.

Fifty-seven well-defined acute stroke patients were investigated for cerebrospinal fluid (CSF) concentrations of zinc (Zn), total protein, and albumin, as well as 6 patients with old infarctions. Significantly increased concentrations were found in patients with acute non-embolic and embolic infarctions and haemorrhage compared with patients having old infarctions or with the controls. The CSF-Zn concentrations in acute infarctions correlated significantly with the total protein and albumin concentrations of CSF. There was no significant difference in the CSF concentrations between the first and second lumbar puncture. The size of the infarctions on CT scan did not correlate with the CSF parameters. High CSF concentrations of Zn, total protein and albumin in acute infarctions related to a poor short-term prognosis. This study shows that CSF-Zn determinations in acute cerebrovascular diseases may be of diagnostic and prognostic value.

Adult↗
PubMed1983

Chromosome integration domain for bovine leukemia provirus in tumors.

The 3'-end host-virus junction fragments from two bovine leukemia virus (BLV)-induced lymphoid tumors (tumors 15-4 and 1351), each containing a single provirus, were used as probes to detect large restriction fragments flanking these proviruses. The DNAs from 28 other independent BLV-induced tumors were checked by Southern analysis of their restriction fragments for possible rearrangement due to the insertion of a BLV provirus in the cellular sequences corresponding to those flanking the proviruses in tumors 15-4 and 1351. In no case did proviral integration occur in cellular sequences corresponding to those implicated in the tumors of origin. According to the statistical analysis performed, if a preferential domain for BLV integration exists, it has a size of 1,304 kilobases when the probability of not observing an integration event in the cellular fragments considered in tumors 15-4 and 1351 is 0.50.

Animals↗
PubMed1983

Optimized atomic absorption spectrophotometry of zinc in cerebrospinal fluid.

This method for direct determination of Zn in cerebrospinal fluid (CSF) involves flame atomic absorption spectrophotometry with a pulse nebulizer technique. Standard solutions of Zn in 150 mmol/L NaCl were used. We could account for 88% of added standard with the method in individual samples from 10 patients and in pooled CSF. The method is acceptably precise, CVs in pooled CSF ranging from 4 to 12%. The mean CSF-Zn concentration for nine healthy men was 0.18 (SD 0.04) mumol/L and for nine healthy women 0.15 (SD 0.03) mumol/L, a statistically insignificant difference. These values are lower than those in previous reports, which may have been the result of contamination problems, nonatomic absorption, or nonstandardized sampling. In the healthy volunteers, the CSF-Zn concentration was positively correlated with serum-Zn, CSF-protein, and CSF-albumin concentrations, as well as with the CSF/serum ratio for albumin.

Adult↗
PubMed1982

Zinc and copper metabolism in phenytoin therapy.

The effect of phenytoin (PHT) on the metabolism of zinc (Zn) and copper (Cu) has been studied during treatment for epilepsy. Eleven previously untreated epileptics were followed from the start of therapy together with 20 patients on long-term therapy. In eight untreated epileptic males low serum concentrations of Zn (S-Zn) were found. At the start of therapy increased S-Zn and S-Cu concentrations were noted. After 1 month of therapy S-Zn was at pretherapy levels but S-Cu was still increased. No changes in the urinary excretion of the metals or in the CSF-Zn concentrations were registered. In the patients on long-term therapy S-Zn was unchanged while S-Cu and S-ceruloplasmin were increased significantly compared with age- and sex-matched controls. It is postulated that the drug may cause a relative zinc deficiency through a chelate binding between Zn and PHT and/or an increased absorption and accumulation of Cu. These effects may be of importance in the development of intoxication symptoms and may also influence the effectiveness of seizure control.

Adult↗
PubMed1982

Zinc and copper in multiple sclerosis.

The serum concentrations of zinc and copper were measured in 50 patients with multiple sclerosis. Lower serum zinc levels were found compared to age- and sex-matched controls. In younger patients low serum copper concentrations were noted. Zinc concentrations in CSF were unchanged. The possibility that malabsorption of the metals causes the low serum concentrations is discussed.

Adult↗