S. D. J. Van Der Werf

Time course and risk factors of post-stroke fatigue: a prospective cohort study

Background:  Post‐stroke fatigue (PSF) often occurs after stroke and has a negative impact on the rehabilitation process. Several studies focused either on short‐ or on long‐term PSF and their relations with stroke characteristics. However, possible pre‐stroke risk factors such as history of depression, pre‐existent white matter lesions or brain atrophy were usually not taken into account. Therefore, the precise mechanisms underlying PSF remain still unclear. This study was aimed at assessing the possible contributions of (pre‐)stroke factors to both short‐term PSF and its course over time.

Fatty acid composition of phospholipids in bile in man: promoting effect of deoxycholate on arachidonate

Ninety-five percent of phospholipids (PLs) in bile is secreted as phosphatidylcholine or lecithin. The study of fatty acid patterns of phospholipids present in gallbladder bile could help clarify whether a preponderance of certain fatty acids could play a role in cholesterol gallstone formation in man. In acute bile acid-exchange experiments, it was found that more hydrophobic bile acids did promote the excretion in bile of PL rich in arachidonic acid (a prostaglandin precursor) and stearic acid. We studied, therefore, bile acid, cholesterol and phospholipid fatty acid patterns (measured by gas chromatography) in gallbladder bile, obtained by duodenal intubation and cholecystokinin-stimulation of 24 healthy volunteers with normal liver/gallbladder function (ultrasound). PL-fatty acid composition (mean % +/- SD) was 41.40 (+/- 1.41) for palmitic acid, 2.68 (+/- 0.82) for palmitoleic acid, 5.50 (+/- 1.55) for stearic acid, 12.09 (+/- 0.98) for oleic acid, 32.83 (+/- 3.04) for linoleic acid and 5.64 (+/- 1.59) for arachidonic acid. The proportion of biliary deoxycholate was positively correlated with arachidonic acid (r = 0.71; p less than 0.01), whereas chenodeoxycholate was inversely correlated with arachidonic acid (r = -0.53; p less than 0.01). There was a positive correlation between biliary chenodeoxycholate and linoleic acid (r = 0.48; p less than 0.05) and a negative correlation between biliary deoxycholate and linoleic acid composition (r = 0.68; p less than 0.01). Also a correlation was found between palmitic acid and cholesterol saturation index (r = 0.49; p less than 0.05). We conclude that the hydrophobic bile acid deoxycholate, which does not desaturate cholesterol in bile, promotes the biliary excretion of arachidonic acid. Since arachidonic acid could induce the gallbladder mucosa to produce prostaglandins and mucus, increased biliary PL-arachidonic acid composition might be a factor in cholesterol gallstone disease.

Arousal, performance and absence seizures in rats

Rats of the WAG/Rij strain show bilateral symmetrical spontaneous spike-wave discharges in the EEG, with clinical concomitants. The present experiment investigated whether, during a learning task, the number of discharges would be diminished compared to a period of rest. Additionally, it was investigated whether behavioural differences would be noticed within the task in trials with and without spike-wave discharges. The length of the post reinforcement pause in a fixed interval task was used as a performance index. Eleven rats were extensively trained to press a lever for food in a fixed (60 sec) interval task until a stable response pattern emerged: a post-reinforcement pause of about half the interval. Next, EEG electrodes were implanted and baseline EEGs were made, before and after the first and fifth test sessions. In addition, the behavior of the animals in the task was monitored when an EEG was recorded. During the task, a significantly smaller number of spike-wave discharges was found, compared to the preceding and succeeding baseline hours. This reduction is probably related to a higher level of vigilance during the task compared to the rest hour. Furthermore, the post-reinforcement pause was significantly enhanced in trials with spike-wave discharges compared to trials without discharges, indicating a clear change in performance. Both results are in agreement with what could be expected in patients with absence epilepsy and provide further evidence for the validation of the spike-wave discharges as genuine epileptic phenomena.

Effect of long term lactulose ingestion on secondary bile salt metabolism in man: potential protective effect of lactulose in colonic carcinogenesis.

This study investigated whether colonic absorption of secondary bile acids, especially deoxycholate in patients with adenomas could be decreased by oral lactulose. Bile acid metabolism was studied using bile sampling and 14C-deoxycholate kinetics in patients with colonic adenomatous polyps before and after four and 12 weeks of lactulose, 60 g/day. The results indicate that lactulose decreased the deoxycholate pool size from a mean of 22.0 (SD: +/- 13.8) to 14.3 (+/- 7.6) mumol/kg (p less than 0.025). Deoxycholate absorption fell from 3.8 (+/- 2.3) to 2.9 (+/- 1.4 mumol/kg/d (ns). The biliary bile acid composition decreased significantly in deoxycholate after four and 12 weeks with a rise in primary bile acids. There was a highly significant correlation between the %-change in DCA input and the %-change in DCA pool size (r = 0.89). Intestinal transit measured by the pellet method (4.1 +/- 1.9 to 2.4 +/- 0.6 day; p less than 0.01) and faecal pH decreased, while stool frequency and weight rose significantly. Significant correlations between the %-change in gut transit time and the %-change in DCA pool size or %-change in DCA input were absent. The results show that it is possible to lower colonic secondary bile acid absorption by long term lactulose feeding. This effect can be mediated by accelerated transit and the acidification of the colonic contents.

Seroepidemiology of gastritis in Japanese and Dutch working populations: evidence for the development of atrophic gastritis that is not related to Helicobacter pylori.

Serological markers of gastritis, like pepsinogen A, pepsinogen C, gastrin, and Helicobacter pylori antibodies, can be used to explore the state of the gastric mucosa in populations with contrasting cancer risks. A decreasing pepsinogen A:C ratio and an increasing serum gastrin are known to reflect an increasing severity of atrophic corpus gastritis, which is a precursor of gastric cancer. In 723 subjects (without gastroduodenal surgery) from Japanese (n = 225) and Dutch (n = 498) working populations, which had a similar composition of age (mean 48 years), sex (male to female ratio 6:1), and type of occupation, fasting serum samples were analysed for IgG antibodies to H pylori, pepsinogen A, pepsinogen C, and gastrin in the same laboratory. H pylori infection was significantly more prevalent in the Japanese than in the Dutch (74.7% and 31.3%); as was a very low pepsinogen A, indicative of severe mucosal atrophy (4.4% and 1.6%). Among subjects with and without severe mucosal atrophy the H pylori seropositivity rate was similar. Between the Japanese and the Dutch there were significant differences in mean gastrin (31.8 and 13.4 pmol/l) and pepsinogen A:C ratio (1.7 and 2.9). These intercountry differences were as great for H pylori negative subjects (gastrin: 23.7 and 10.3 pmol/l, pepsinogen A:C ratio: 2.4 and 3.2) as for H pylori positive subjects (gastrin: 34.6 and 20.1 pmol/l, pepsinogen A:C ratio: 1.5 and 2.5). The intercountry difference in gastrin nearly disappeared after stratification into categories of pepsinogen A:C ratio. In conclusion, the intercountry differences in pepsinogen A:C ratio and gastrin reflect a higher prevalence of mild and severe mucosal atrophy of the corpus in the Japanese than in the Dutch, both among H pylori positive and negative subjects. Thus, these findings suggest that in the Japanese the development of atrophic gastritis is in part unrelated to H pylori.

Influence of Age, Intestinal Transit Time, and Dietary Composition on Fecal Bile Acid Profiles in Healthy Subjects

Bacterial transformation of bile acids is possibly involved in colorectal carcinogenesis. In several epidemiological studies, the secondary bile acid concentration in feces is related to the incidence of colonic cancer. However, data on fecal bile acids in case-control studies are conflicting. We investigated the influence of age, intestinal transit time, and dietary composition on fecal bile acid profiles in healthy subjects of three different age groups (mean ages 22, 48, and 67 years). Fecal bile acids were analyzed by gas-liquid chromatography. The concentration of the major secondary fecal bile acids increased with advancing age and was significantly higher in elderly subjects, compared to young adults. The concentration in middle-aged persons was intermediate. Analysis of dietary constituents showed that the fat intake in the three groups was comparable. The dietary fiber intake in elderly subjects was significantly lower than in the other two groups. The former group did excrete less dry fecal material compared to both other groups. Dietary fiber intake was negatively correlated with the total bile acid concentration. Probably, a decrease in dietary fiber intake results in higher fecal bile acid concentrations with advancing age. From the findings of this study, it is obvious that matching for age is important when case-control studies concerning the role of fecal bile acids in colorectal carcinogenesis are conducted.

Serum lipids, biliary lipid composition, and bile acid metabolism in vegetarians as compared to normal controls

Abstract. Since dietary factors have been implicated in various diseases, such as coronary heart disease, gallstone formation and colonic cancer, possibly by affecting cholesterol and bile acid metabolism, we studied serum lipid levels, biliary lipid composition, cholic acid and deoxycholic acid kinetics in a group of young healthy male vegetarians and in age, sex and weight matched control subjects. Daily intake of nutrients was higher with respect to polyunsaturated fatty acids, carbohydrates and dietary fibre in the vegetarian group. Although mean serum lipid levels in the vegetarian were 8–28% lower than in the control subjects, differences were not statistically significant. Biliary lipid and biliary bile acid composition were similar in both groups. Bile acid kinetics, measured after simultaneous injection of [3H] cholic acid and [14C]deoxycho‐lic acid, showed a slightly lower output of cholic acid and a slightly higher input of deoxycholic acid in the vegetarians, this causing a significantly (P < 0025) higher 7α‐dehydroxylation fraction (input deoxycholic acid divided by synthesis of cholic acid) in the vegetarians. Our results in young males suggest that bile acid conservation is associated with a vegetarian diet, but do not support the supposition that a vegetarian diet reduces deoxycholate formation.

Effects of a standardized wheat bran preparation on biliary lipid composition and bile acid metabolism in young healthy males

Abstract. The effects of adding bran to the normal diet on biliary lipid composition and bile acid metabolism in a group of young healthy males was studied. A chemically standardized coarse wheat bran product, with serum lipid lowering properties, in a dose of 0–5 kg‐1 body weight per day was used. Bran feeding for 4 or 8 weeks did not change biliary lipid and biliary bile acid composition. Faecal bile acid and neutral sterol composition was similar before and after 8 weeks of bran. Bile acid kinetics, measured by double isotope dilution after simultaneous injection of [3H]cholic acid and [14C]deoxychoIic acid, showed only minor differences before and during bran ingestion. The most surprising finding was an increase in 7α‐dehydroxyl‐ation fraction (input of deoxycholic acid divided by synthesis of cholic acid) in six out of seven subjects after 4 weeks of bran and in all four subjects after 8 weeks of bran. In conclusion, the bran product we used is not effective in lowering the biliary cholesterol saturation in healthy young males. Nor does it reduce deoxycholate input in our subjects even after 8 weeks of bran.

Biliary lipids, bile acid metabolism, gallbladder motor function and small intestinal transit during ingestion of a sub-fifty oral contraceptive

The risk of developing gallstone disease while using low dose oral contraceptives (OC) has been incompletely explored in man. In this study, biliary lipid composition, bile acid conjugation, primary bile acid kinetics, gallbladder storage and emptying by quantitative cholescintigraphy, and small intestinal transit by breath hydrogen analysis are reported in a group of non-obese healthy young women, both after 3-5 months OC, using 30 micrograms ethinyl oestradiol daily, and during an adjacent control period. OC use was associated with a significant rise of biliary cholesterol saturation in gallbladder bile. Total bile acid pool size did not change; however, mean cholic acid pool size was 36% greater than in the control period (P less than 0.001), due to its enhanced synthesis rate, at the expense of chenodeoxycholic acid and deoxycholic acid pool sizes (P less than 0.05). A rise in taurine conjugation of biliary bile acids was apparent in all subjects (P less than 0.0001). Gallbladder motor function was not influenced by ingestion of OC, whereas only a minor retardation of small intestinal transit was found. The findings show an effect of this sub-50 OC on biliary lipid composition and cholesterol saturation that is comparable with that of conventional OC. The predominance of more hydrophilic bile acid conjugates during oral contraception is in keeping with a hepatic effect of this preparation on bile acid metabolism.

Evaluation of colour vision, mesopic vision, visual evoked potentials and lightness discrimination in adult amblyopes

This is a study conducted on thirty adult strabismic and anisometropic amblyopes using colour vision tests, the lightness discrimination test, mesopic vision and visual evoked responses, in order to determine the probable site of the amblyopic defect. The results showed that, in its progressed stages, amblyopia is associated with eccentric fixation, abnormal hue discrimination, disturbed lightness discrimination and mesopic vision, and attenuation of the amplitude of the pattern visual evoked response. It is suggested that these abnormalities result from a defect involving the extrastriate higher visual association areas 18 & 19 of Brodmann.