Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder.

BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.

Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion.

To compare the disposition of 5-aminosalicylic acid (5-ASA) and its acetylated metabolite during treatment with olsalazine and mesalazine, 14 patients with inactive ulcerative colitis were randomly assigned to olsalazine (1 g twice daily) and the mesalazines, Asacol (800 + 400 + 800 mg daily), Pentasa (750 + 500 + 750 mg daily), and Salofalk (750 + 500 + 750 mg daily) in a crossover design trial so that all received each drug for seven days. Intraluminal colonic concentrations of 5-ASA were estimated after five days by the method of equilibrium in vivo dialysis of faeces. A predose serum sample and a 24 hour urine collection were obtained on day seven. The 5-ASA and acetyl-5-aminosalicylic acid (Ac-5-ASA) values were determined by high performance liquid chromatography. Olsalazine almost doubled the colonic concentrations (mean 23.7 (SEM) (1.9) mmol/l) of its therapeutically active ingredient (5-ASA) compared with equimolar doses of Pentasa (12.6 (2.2) mmol/l; p less than 0.0003) and Salofalk (15.0 (2.0) mmol/l; p less than 0.003). At the same time, olsalazine treatment was associated with lower serum concentrations and urinary excretions (p less than 0.05) of 5-ASA and Ac-5-ASA compared with the mesalazine preparations. The low systemic load of 5-ASA provided by olsalazine reduces the potential risk of nephrotoxicity during long term treatment.

Aetiology, medical history, and faecal weight in adult patients referred for diarrhoea. A prospective survey.

All patients referred for diarrhoea over a 2-year period were studied to determine the relative frequency of organic diarrhoea and functional disorder. One hundred and nine patients had diarrhoea of established aetiology at admission. Two hundred and one patients with diarrhoea of unestablished aetiology at admission were interviewed about symptoms, and faecal output was measured. An organic or other explanation was eventually found in 78 patients (39%), whereas the bowel symptoms were categorized as functional or transient in 58%. Chronic diarrhoea of unknown origin was seen in 3%. Only 40% of the patients referred for diarrhoea had faecal output greater than 200 g/day. A reliable differentiation between organic and functional diarrhoea based solely on history and a physical examination at admission was not possible, as the initial diagnostic guess was only confirmed in 42% of the patients. More sensitive and specific indicators of functional diarrhoea are needed before the patients can be safely classified without the need for thorough diagnostic study.

Zinc in mononuclear leucocytes in alcoholics with liver cirrhosis or chronic pancreatitis and in patients with Crohn's disease before and after zinc supplementation.

Mononuclear leucocyte zinc was determined together with serum zinc, albumin and serum alkaline phosphatase activity before and after zinc supplementation (2 x 50 mg of zinc-gluconate daily during 3 months) in patients with alcoholic liver cirrhosis (n = 10), alcoholic chronic pancreatitis (n = 10) and Crohn's disease (n = 10). Initial mononuclear leucocyte zinc concentrations did not differ between the patient groups and the reference group (n = 10), whereas initial serum zinc values were lower in the patients with alcoholic liver cirrhosis and Crohn's disease. This difference disappeared, however, when serum zinc concentrations were corrected for albumin levels, which were lower in all the patient groups. Higher initial activity of serum alkaline phosphatase was found in the alcoholic patients. In all the patient groups serum zinc concentrations increased significantly after zinc supplementation. Only in patients with Crohn's disease was there also an increase in serum alkaline phosphatase and albumin. Mononuclear leucocyte zinc did not respond to zinc supplementation in any of the patient groups. The results of our study indicate that mononuclear leucocyte zinc is not a sensitive indicator of marginal zinc deficiency.

Prevalence of surreptitious laxative abuse in patients with diarrhoea of uncertain origin: a cost benefit analysis of a screening procedure.

The costs and medical benefits of an early, routine laxative screening test in patients with diarrhoea of uncertain origin was evaluated. During a two year period 200 consecutive, unselected patients complaining of diarrhoea were considered for the study in whom a three day faecal collection was undertaken. Fifty four patients denying laxative consumption had diarrhoea (mean daily stool weight greater than 200 g) of uncertain origin at their initial visit of whom 47 were screened to detect ingestion of anthraquinones, bisacodyl, phenolphthalein, and magnesium salts. Seven patients had positive tests. No single clinical feature could have predicted the outcome of the test. The possible cost savings of the programme were estimated by not releasing the results of the test to the clinicians until the patient's investigations were complete. The seven patients with laxative abuse spent a total of 35 days in hospital and were seen on 29 occasions in the outpatient clinic after the laxative screening test was positive. The cost of the screening programme was cheaper than the costs of the diagnostic procedures in patients with laxative abuse. We recommend the use of a comprehensive, early laxative screening programme in all patients with diarrhoea of uncertain origin as a cost effective procedure.