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ObjectiveLong-term studies regarding the effect of a structured physical exercise programme (SPEP) during haemodialysis (HD) assessing compliance and clinical benefit are scarce.Study designA single-centre clinical trial, non-randomised, investigating 46 patients with HD (63.2±16.3 years, male/female 24/22, dialysis vintage 4.4 years) performing an SPEP over 5 years. The SPEP (twice/week for 60 min during haemodialysis) consisted of a combined resistance (8 muscle groups) and endurance (supine bicycle ergometry) training. Exercise intensity was continuously adjusted to improvements of performance testing. Changes in endurance and resistance capacity, physical functioning and quality of life (QoL) were analysed over 1 year in addition to long-term adherence and economics of the programme over 5 years. Average power per training session, maximal strength tests (maximal exercise repetitions/min), three performance-based tests for physical function, SF36 for QoL were assessed in the beginning and every 6 months thereafter.Results78% of the patients completed the programme after 1 year and 43% after 5 years. Participants were divided—according to adherence to the programme—into three groups: (1) high adherence group (HA, >80% of 104 training sessions within 12 months), (2) moderate adherence (MA, 60–80%), and 3. Low adherence group (LA, <60%)) with HA and MA evaluated quantitatively. One-year follow-up data revealed significant (p<0.05) improvement for both groups in all measured parameters: exercise capacity (HA: 55%, MA: 45%), strength (HA: >120%, MA: 40–50%), QoL in three scores of SF36 subscales and physical function in the three tests taken between 11% and 31%. Moreover, a quantitative correlation analysis revealed a close association (r=0.8) between large improvement of endurance capacity and weak physical condition (HA).ConclusionsThe exercise programme described improves physical function significantly and can be integrated into a HD routine with a high long-term adherence.

The effect of six different structurally modified sphingosine analogues on biosynthesis of sphingolipids was studied in primary cultured murine cerebellar neurons. Treatment of cells with cis-4-methylsphingosine at micromolar levels resulted in a markedly decreased sphingolipid biosynthesis, whereas the other compounds examined, trans-4-methylsphingosine, cis-5-methylsphingosine, trans-5-methylsphingosine, cis-sphingosine, and 1-deoxysphingosine, inhibited sphingolipid biosynthesis less efficiently. The inhibition of sphingolipid biosynthesis by the various compounds was paralleled by a decrease of serine palmitoyltransferase activity in situ. For cis-4-methylsphingosine the inhibitory effect on serine palmitoyltransferase activity was shown to be concentration-and time-dependent. Half-maximal reduction of enzyme activity occurred after 24 h of treatment with 10 M of the compound. The activity of other enzymes of sphingolipid biosynthesis as well as phospholipid and protein biosynthesis was not affected.Analysis of the sphingoid moiety of cellular sphingolipids suggests that the sphingosine analogues listed above were subject to degradation rather than being utilized as precursors for sphingolipid biosynthesis by cultured neurons. Except of 1-deoxysphingosine, the other five sphingosine analogues were shown to be substrates for sphingosine kinase in vitro. After 24 h of treatment of primary cerebellar neurons with the various sphingosine analogues the relative percentage of the respective intracellular 1-phosphate derivatives paralleled exactly the inhibitory effect on serine palmitoyltransferase activity observed when cells were treated with the unphosphorylated compounds. In contrast to the respective 1-phosphate derivatives of the other methyl-branched sphingosine analogues examined, cis-4-methylsphingosine 1-phosphate showed an intracellular accumulation suggesting a delayed turnover rate in cultured murine neurons for this compound. These results suggest that the inhibitory effect of the sphingosine analogues on serine palmitoyltransferase is mediated by their respective 1-phosphate derivatives and that the pronounced effect of cis-4-methylsphingosine is caused by a high intracellular concentration of cis-4-methylsphingosine 1-phosphate. cis-4-Methylsphingosine, in addition, caused drastic changes in cell morphology of primary cerebellar neurons, which were not observed when these cells were treated with one of the other sphingosine analogues examined.

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Background: The aim of this epidemiological study is to examine the prevalence and correlates of psychotropic drug use in the very old and to evaluate the appropriateness of psychotropic drug use in very old age.Methods: Data from the Berlin Aging Study (BASE), a multidisciplinary study of an age- and gender-stratified, randomly selected sample of elderly people living in Berlin are presented. Over-sampling, especially very old men, allows for powerful analyses of this population. All participants went through extensive psychiatric and somatic examinations. Medication intake was assessed by different data sources (interviewing patients and their family physicians, drug inspection at home). Results were brought together in a consensus-conference and research physicians gave operationalized ratings of medication appropriateness.Results: The prevalence of elderly people who were taking at least one psychotropic medication within the 14 days immediately preceding investigation was 29.8%. Of these medications, 68.4% had been taken for longer than one year. There was no effect of age or gender on the scope of psychotropic drug use. Benzodiazepines were taken by 19.8% of the elderly. Antidepressants, neuroleptics and anti-dementia drugs were taken by about 3–4% each. People taking psychotropic drugs had significantly higher levels of psychiatric morbidity, as measured by syndromes and specified diagnoses. Psychotropic drugs were significantly less often judged to be indicated than somatic medications. This is mostly due to benzodiazepines.Conclusions: Psychotropic drug use is common in old age, but there is no additional increase in usage beyond the age of 70. Intake of psychotropics is mostly oriented at symptoms or syndromes, which explains why benzodiazepines are still the most commonly prescribed psychotropics