Biomedical subjects

A M Smit

Publications and source records attributed to A M Smit.

At least 19 recordsLinked to original sources

PubMed1998

Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses.

BACKGROUND/AIMS: Ursodeoxycholic acid has been reported to be of potential benefit for primary sclerosing cholangitis but little is known about the long-term biochemical, histological and radiological efficacy or the optimum frequency of ursodeoxycholic acid administration. METHODS: A 2-year multicentre randomised controlled trial was initiated to assess the effects of ursodeoxycholic acid (10 mg kg(-1).d(-1), given in either single or multiple daily doses, on symptoms, serum liver tests, cholangiographic and histological findings and the occurrence of treatment failure. Liver biopsies were taken and endoscopic retrograde cholangiography was performed at entry and after 2 years; follow-up examinations were at 3-month intervals. Treatment failure was defined as death, liver transplantation, 4-fold increase in serum bilirubin, variceal bleeding, de novo ascites or cholangitis. Actuarial survival was compared with predicted survival using the revised Mayo natural history model for primary sclerosing cholangitis. RESULTS: Forty-eight patients were enrolled. In one case, ursodeoxycholic acid had to be discontinued because of gastro-intestinal complaints. No other side-effects were observed. After 2 years of follow-up, treatment was not associated with a beneficial effect on either symptoms or liver histology. Serum liver tests (alkaline phosphatase, y-glutamyl transferase, aspartate aminotransferase) improved significantly in both groups, while serum bilirubin (which was near normal at entry) and IgG remained stable. No major changes in radiographic bile duct appearance seemed to be present. After 2 years, actuarial survival was 91% (95 CI 83%-99%), which is comparable to the predicted 97% survival rate. Treatment failure occurred in 15% of cases. No significant differences in any of the study endpoints (symptoms, serum liver tests, cholangiographic findings, histology, disease progression) were found between the two groups. CONCLUSIONS: Ursodeoxycholic acid is well tolerated in primary sclerosing cholangitis. Significant effects on biochemical parameters were found and symptoms, bilirubin and histology did not deteriorate. No advantage of a multiple daily dose over a single dose was observed.

Adult↗

PubMed1998

Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1-year randomized, placebo-controlled study.

BACKGROUND/AIMS: Treatment with ursodeoxycholic acid has been shown to decrease the rate of disease progression in patients with primary biliary cirrhosis, although the effect is modest. Since primary biliary cirrhosis has many features of an autoimmune disorder, immunosuppressives added to ursodeoxycholic acid may be of value in the treatment of primary biliary cirrhosis. METHODS: A 1-year randomized, double-blind, placebo-controlled trial was carried out in 50 patients with primary biliary cirrhosis, who had already been treated with ursodeoxycholic acid for at least 1 year, but had not achieved complete disease remission. Patients were randomized to additional prednisone (30 mg per day initially, tapered to 10 mg daily after 8 weeks) and azathioprine (50 mg daily) or placebo. A subgroup of patients received cyclical etidronate and calcium. The principal aim of the study was to assess the short-term benefits and risks of the combined bile acid and low-dose immunosuppressive regimen. Primary endpoints were effects on symptoms, liver biochemistry, liver histology, bone mass and the occurrence of adverse events. RESULTS: Pruritus (p=0.02), alkaline phosphatase, aspartate aminotransferase, IgM and procollagen-III-propeptide improved significantly (all p<0.002) in the combined treatment group as compared to the placebo group. Histological scores for disease activity and disease stage decreased significantly within the combination treatment group (p<0.001). CONCLUSIONS: In patients with primary biliary cirrhosis receiving ursodeoxycholic acid, there is an additional beneficial effect of 1-year treatment with prednisone and azathioprine on symptoms and biochemical, fibrogenetic and histological parameters. These results strongly encourage the evaluation of this triple treatment regimen in long-term controlled trials of adequate size to document its effect on clinical events.

Adult↗

PubMed1998

A randomized trial in primary biliary cirrhosis comparing ursodeoxycholic acid in daily doses of either 10 mg/kg or 20 mg/kg. Dutch Multicentre PBC Study Group.

BACKGROUND: Ursodeoxycholic acid (UDCA) prolongs transplantation-free survival in primary biliary cirrhosis (PBC). However, the optimal therapeutic dose has not been established. AIM: To compare the effects of UDCA administered in daily doses of 10 vs. 20 mg/kg on symptoms, liver biochemistry and biliary UDCA enrichment. METHODS: A 6-month multicentre randomized open controlled trial was conducted to assess the effects of an increase in the dose of UDCA to 20 mg/kg/day vs. continuation of 10 mg/kg/day for patients who had not achieved biochemical normalization during treatment for at least 6 months with the 10 mg/kg dose. Clinical and laboratory evaluations were performed at entry and at 3-month intervals. The percentage UDCA in duodenal bile was assessed at entry and at 6 months. RESULTS: Sixty-one patients were enrolled. No side-effects of UDCA were observed. Within the 20 mg/kg/day group significant decreases were found for alkaline phosphatase (- 8%; P = 0.003), aspartate aminotransferase (- 11%; P = 0.01), alanine aminotransferase (- 17%; P < 0.001), gamma-glutamyl transferase (- 34%; P < 0.001), immunoglobulin M (- 11%; P = 0.002) and cholesterol (- 8.1%; P < 0.001). In the 10 mg/kg group none of these parameters differed significantly from baseline. No significant differences between dose groups for symptom scores or serum bilirubin were found. Biliary enrichment with UDCA increased from 37% to 46% in the 20 mg/kg group (P = 0.02) while remaining stable in the 10 mg/kg group. CONCLUSIONS: Liver biochemistry improved in PBC patients receiving UDCA 20 mg/kg/day compared to a dose of 10 mg/kg/day. Both doses were equally well tolerated. These results indicate that UDCA 10 mg/kg/ day is a suboptimal dose for treating PBC.

Adult↗

PubMed1997

Oral glucose clearance in 12-year-old South Africans.

A portable glucometer method was used to measure clearance of salivary glucose in 31 black and in 28 white 12-year-old school children. The aims of this study were to evaluate a readily available portable glucometer method and to investigate salivary glucose clearance as a marker of caries risk. Following the initial evaluation, we adapted the portable adapted glucometer method and found it reproducible and suitable for the measurement of salivary glucose clearance. Black children had almost double the salivary clearance rates of white children. No significant differences in salivary glucose clearance were seen between caries free (DMFT = 0) and caries active (DMFT > or = 3) children. Salivary glucose clearance is not suitable as a single caries risk predictor.

Black People↗

PubMed1990

The acute effects of glucosidase inhibition on post-meal glucose increments in insulin-dependent diabetics.

The effects of glucosidase inhibition on postprandial glucose tolerance was studied in 11 insulin-dependent diabetics. In comparison with placebo, 50 mg miglitol was able to lower the incremental glucose response significantly at 30 minutes and 60 minutes when insulin was injected: (i) 30 minutes before the meal (2,3 +/- 0,5 mmol/l v. 0,37 +/- 0,2 mmol/l; P less than 0,001; and 5,0 +/- 0,7 mmol/l v. 1,1 +/- 0,8 mmol/l; P less than 0,001); and (ii) immediately before the meal (2,3 +/- 0,5 mmol/l v. 2,2 +/- 0,9 mmol/l; P less than 0,001) respectively. The incremental glucose area under the curve when insulin was injected 30 minutes before breakfast was also significantly reduced on miglitol in comparison with placebo (0,67 +/- 0,15 mmol/l v. 0,16 +/- 0,14 mmol/l; P less than 0,01). The effect of miglitol was more evident when insulin was injected 30 minutes before rather than immediately before the meal. No significant adverse effects were encountered. It is concluded that: (i) miglitol safely reduces the early post-meal glucose increments in insulin-dependent diabetics; and (ii) its effect enhances the hypoglycaemic response of an appropriately timed injection of insulin.

1-Deoxynojirimycin↗

PubMed1990

On-line detection of transient neuropsychological disturbances during EEG discharges in children with epilepsy.

Short-term memory tasks (visual-spatial and verbal) were devised to identify the influence of transient EEG discharges, without clinically manifest disturbances, on neuropsychological performance. 53 children with subclinical focal and generalized EEG discharges were tested 72 times and 16-channel telemetered EEG and video-recordings were made. 36 per cent of test sessions showed a significant preponderance of errors when discharges were recorded. Children with right-sided discharges had impaired performance in 50 per cent of their test sessions, with performance on the visual-spatial task most affected: left-sided discharges appeared to exert greater influence on the verbal task. These tests can easily be used to monitor six- to 15-year-old children.

Adolescent↗

PubMed1987

[Schistosomiasis mansoni as an imported disease in The Netherlands].

Explore the source record for details and available documents.

Adolescent↗

PubMed1987

The influence of subclinical epileptiform EEG discharges on driving behaviour.

EEG and driving behaviour were monitored in 6 patients with subclinical focal and generalised epileptiform EEG discharges during 420 km of actual motorway driving in a suitably instrumented vehicle. Evidence of impaired driving performance during subclinical discharges was significant in 3 subjects (P less than 0.025 or less than 0.05) and was suggestive (P less than 0.1) in 1. The two patients with greatest impairment had active epilepsy, whereas the others had been seizure-free for upwards of 4 years. No other features appeared to be predictive of altered driving behaviour during discharges.

Adult↗

PubMed1987

Interactions of epileptiform EEG discharges and cognition.

Interactions of subclinical epileptiform EEG discharges and cognitive functioning were studied in 91 patients with epilepsy, under video monitoring, to exclude overt clinical ictal phenomena during the investigations. A short-term memory test was presented as an engaging television game, in two versions, using spatial, or verbal material. Transitory cognitive impairment (TCI) was demonstrated during EEG discharges, either generalised or focal, in half the patients. Right-sided discharges were associated with impairment of the spatial task and left-sided with errors on the verbal version. TCI was demonstrable only when the discharge occurred during presentation of the material to be recalled. Increasing task difficulty, up to the patients' limit of performance, was associated with increasing susceptibility to TCI. Sixteen patients showed a significant effect of task on discharge rate, but in some this increased during the stimulus and in others while responding. There are thus complex interactions of epileptiform EEG activity on cognitive function and vice versa.

Adolescent↗

PubMed1986

Fatty acid induced changes in circulating total and free thyroid hormones: in vivo effects and methodological artefacts.

Elevated levels of nonesterified fatty acids (NEFA) are frequently found in acute illnesses, and they may contribute to changes in serum thyroid hormone concentrations in nonthyroidal illnesses (NTI) by displacing protein bound hormones. We therefore examined the effects of low and raised plasma NEFA levels on circulating total and free thyroxine (TT4 and FT4) and triiodothyronine (TT3 and FT3) concentrations, the Free T4 Index (FT4I) and TSH, in a randomized crossover study in 10 normal subjects. Subjects ate either a high carbohydrate breakfast (low NEFA protocol) or a high fat breakfast followed by an iv injection of 1000 u heparin (high NEFA protocol). Possible biological effects of changes in FT4 and FT3 were evaluated by a 200 micrograms iv TRH test. Free T4 and T3 were measured by a direct analogue method (AFT4 and AFT3). In a similar high NEFA study, but without TRH, FT4 was also measured by equilibrium dialysis (DFT4) and a 2-step RIA method (2-step FT4). Acute elevations of plasma NEFA from 0.67 +/- 0.08 mmol/L to a peak of 2.6 +/- 0.54 mmol/L resulted in a prompt reciprocal fall of mean TT4 (-8.7%, p less than 0.01), AFT4 (-30%, p less than 0.005) and TT3 (-11.5%, p less than 0.01) and AFT3 (-16%, p less than 0.005); DFT4 rose significantly from 23.7 +/- 1.9 pmol/L to 33.0 +/- 3.7 pmol/L (+39%, p less than 0.025) and 2-step FT4 rose by 16% (p less than 0.05). TSH levels declined consistently from 3.3 +/- 0.5 mIU/L to 2.6 +/- 0.4 mIU/L (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

PubMed1986

Thyroid hormone and carrier protein interrelationships in children recovering from kwashiorkor.

We have studied 15 infants with severe protein energy malnutrition (PEM) as a model of nutritional nonthyroidal illness. Changes in circulating thyroid hormones, binding proteins, and their interrelationships were assessed before and during recovery. Serum concentrations of total thyroxine and triiodothyronine and of thyroxine-binding proteins were extremely reduced, and increased progressively during 3 wk of refeeding. The T4:TBG molar ratio was initially 0.180 +/- 0.020, and increased progressively, parallel to the increases in TT4, to 0.344 +/- 0.038 after 21 days (p less than 0.025). The changes in free T4 estimates varied according to the methods used--FTI and analogue FT4 increased, dialysis FT4 fraction decreased. Serum TSH levels increased transiently during recovery. It is concluded 1) there is reduced binding of T4 and T3 to TBG in untreated PEM which takes 2-3 wk to recover; 2) there are methodological differences in evaluating free T4 levels in PEM; 3) increased TSH secretion appears to be an integral part of the recovery from PEM.

Carrier Proteins↗

PubMed1984

Selective cognitive impairment during focal and generalized epileptiform EEG activity.

It is well established that generalized epileptiform EEG discharges unaccompanied by overt clinical change may nevertheless be associated with transitory cognitive impairment (TCI) detectable by appropriate psychological testing. However, the tests employed in most research studies of this phenomenon are of little use for routine clinical application. They are suitable for administration only over short periods of time and are therefore applicable only to patients with a high discharge rate, a serious limitation, as the discharges are generally depressed by the tests themselves. We have developed two short-term memory tasks, one using verbal, the other nonverbal material presented in the form of television games which patients are generally prepared to perform for up to an hour or longer. Forty-six patients with subclinical EEG discharges have been studied. They were screened by video monitoring before and during testing to exclude any with overt clinical changes during the discharges. Despite this rigorous selection, in 50 per cent TCI was demonstrable with a confidence level (within the individual patient) of 10 per cent. Discharges during stimulus presentation were most disruptive of performance and those confined to the period when the patient was responding were without demonstrable effect. A significant association was found between the laterality of focal or asymmetrical generalized discharges and impairment of one or other task, left-sided discharges being associated with errors in the verbal task and right-sided with impairment of the nonverbal test. Two case histories are cited illustrating patients who were clearly handicapped by TCI and whose functioning improved when the subclinical discharges were suppressed by medication. To determine how many patients suffer such disabilities or can be helped by appropriate medication, further prospective studies are required.

Adolescent↗

PubMed1982