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Biomedical subjects

M van den Berg

Publications and source records attributed to M van den Berg.

At least 19 recordsLinked to original sources
PubMed2006

Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer.

Gastric cancers express enhanced levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Single-nucleotide polymorphisms (SNPs) in MMP and TIMP genes may be associated with disease susceptibility and might also affect their antigen expression. We studied the genotype distribution and allele frequencies of SNPs of MMP-2, -7, -8 and -9 and TIMP-1 and -2 in gastric cancer patients in relation to tumour progression, patient survival and tissue antigen expression. The genotype distribution and allele frequencies were similar in gastric cancer patients and controls, except for MMP-7(-181A>G). In addition, the genotype distribution of MMP-7(-181A>G) was associated with Helicobacter pylori status (chi(2) 7.8, P=0.005) and tumour-related survival of the patients. Single-nucleotide polymorphism TIMP-2(303C>T) correlated significantly with the WHO classification (chi(2) 5.9, P=0.03) and also strongly with tumour-related survival (log rank 11.74, P=0.0006). Single-nucleotide polymorphisms of MMP-2, -8, -9 and TIMP-1 were not associated with tumour-related survival. Only the gene promoter MMP-2(-1306C>T) polymorphism correlated significantly with the protein level within the tumours. First-order dendrogram cluster analysis combined with Cox analysis identified the MMP-7(-181A>G) and TIMP-2(303C>T) polymorphism combination to have a major impact on patients survival outcome. We conclude that MMP-related SNPs, especially MMP-7(-181A>G) and TIMP-2(303C>T), may be helpful in identifying gastric cancer patients with a poor clinical outcome.

Adult↗
PubMed2006

In vivo and in vitro Ah-receptor activation by commercial and fractionated pentabromodiphenylether using zebrafish (Danio rerio) and the DR-CALUX assay.

The present study addresses the toxicity of a commercial pentabrominated diphenylether (PeBDE) flame retardant mixture, DE-71, in a model aquatic vertebrate. Four weeks' exposure of juvenile zebrafish (Danio rerio) to water-borne DE-71 resulted in dose-dependent induction of CYP1A immunoreactivity, predominantly in the endocardium and the endothelium of larger blood vessels, such as ventral aorta and branchial arteries, as well as the larger hepatic and pancreatic blood vessels. To investigate the impact of possible contaminating PBDD/Fs in the DE-71 product, the study was repeated after DE-71 had been fractionated into a non-planar (cleaned PBDEs) and a planar fraction (PBDD/Fs). Zebrafish were exposed under similar conditions to the planar and cleaned DE-71 fractions, and to uncleaned DE-71. In addition, the above fractions were chemically analyzed and tested in a reporter gene assay (DR-CALUX) for their aromatic hydrocarbon-receptor (AhR) stimulating potencies. A relatively strong CALUX response was detected from the planar DE-71 fraction (19.7ng TCDD equivalent (TEQ)/g DE-71), coinciding with a strong induction of CYP1A immunoreactivity in zebrafish. CYP1A immunoreactivity in zebrafish exposed to uncleaned DE-71 was intense, although the CALUX response was 10-fold less compared to the planar fraction. Only weak CYP1A immunoreactivity was found in fish exposed to cleaned DE-71, and none in control animals; no CALUX response was detected in cleaned DE-71. The present findings indicate that chemical impurities of the commercial PeBDE product account for AhR-mediated effects. Analytical isolation of a planar fraction from the commercial product increased the in vitro (DR-CALUX) signal 10 times. Immunohistochemistry showed a strong tissue specific reaction to DE-71 in vivo at these relatively low TEQ levels regardless of chemical pretreatment of the mix, reflecting the sensitivity of CYP1A induction in juvenile zebrafish to AhR agonists.

Animals↗
PubMed2006

Antagonism of TCDD-induced ethoxyresorufin-O-deethylation activity by polybrominated diphenyl ethers (PBDEs) in primary cynomolgus monkey (Macaca fascicularis) hepatocytes.

Polybrominated diphenyl ethers (PBDEs) are widespread environmental pollutants, and the levels of certain congeners have been increasing in biota and abiota in recent decades. Some PBDEs are lipophilic and persistent, resulting in bioaccumulation in the environment. Their structural similarity to other polyhalogenated aromatic hydrocarbons (PHAHs) such as polychlorinated biphenyls (PCBs) has raised concerns that PBDEs might act as agonists for the aryl hydrocarbon receptor (AhR). Recent studies in our laboratory with human and rat cell lines indicated no AhR mediated CYP1A1 induction for PBDEs. However, an earlier in vitro study by Van der Burght et al. (1999) [Van der Burght, A.S., Clijsters, P.J., Horbach, G.J., Andersson, P.L., Tysklind, M., van den Berg, M., 1999. Structure-dependent induction of CYP1A by polychlorinated biphenyls in hepatocytes of cynomolgus monkeys (Macaca fascicularis). Toxicol. Appl. Pharmacol. 155, 13-23] indicated that in cynomolgus monkey (M. fascicularis) hepatocytes PCBs with a non-planar configuration could induce CYP1A. As PBDEs show a structural similarity with non-planar (ortho substituted) PCBs, our present study focused on the possible CYP1A induction by PBDEs (BDE-47, -99, -100, -153, -154, -183, and -77) in individual preparations (n=4) of primary hepatocytes of cynomolgus monkeys (M. fascicularis). 7-Ethoxyresorufin-O-deethylase (EROD) was used as a marker for CYP1A-mediated catalytic activity. Cells were exposed for 48 h to various PBDE concentrations (0.01-10 microM), positive controls 2,3,7,8-TCDD (0.001-2.5 nM) and PCB-126 (0.01-10nM), and negative control (DMSO vehicle alone). No statistically significant induction of CYP1A was observed in the hepatocytes after 48 h of exposure to all environmentally relevant PBDEs. After exposing hepatocytes to PBDEs in combination with TCDD, a concentration-dependent decrease in TCDD-induced EROD activity was observed. All PBDEs tested showed a similar reduction in each of four experiments, though quantitative differences were observed. The observed antagonism of TCDD-induced EROD activity by PBDEs occurred in both male (n=3) and female (n=1) hepatocytes and was not due to catalytic inhibition of EROD activity or cytotoxicity. However, based on the results of this study we do not expect these antagonistic effects of PBDEs on CYP1A induction at environmental relevant levels, since these in vitro interactive effects with TCDD were observed only at relatively high concentrations that are normally not seen, e.g. in the human body.

Animals↗
PubMed2006

A local and regional Alcohol and Drugs Monitor in the Netherlands: a tale of three cities.

Local and regional policymakers, care providers and prevention workers involved in addiction and addiction care need timely and reliable information. As few data on substance use are available at a local or regional level, an integrated local or regional monitoring system for alcohol and drugs (MAD) was developed. The MAD consists of four modules: a local social and information map, analyses of registration data of (addiction) care organisations, a local/regional survey among the general population and a community-based drug monitoring system aimed at collecting data on hard drug users. Both quantitative and qualitative research methods are used. This paper presents an overview of the MAD results with respect to alcohol and illicit drug use. Both quantitative and qualitative results show a substantial variation between regions, even in a country as small as the Netherlands. The study shows that a monitoring system can be an important source of information for local addiction policy, care and prevention.

Adolescent↗
PubMed2006

Hemophilia joint health score reliability study.

UNLABELLED: Measurement of joint health is critically important when assessing children with haemophilia. Few measures exist; they lack sensitivity to small changes, don't account for normal development and were never formally validated. To address these concerns, the Hemophilia Joint Health Score (HJHS) was developed by modifying existing scores. OBJECTIVE: To test the inter-observer and test-retest reliability of the HJHS. METHODS: Using a fully factorial design, four physiotherapists (from Canada, the United States and Sweden) examined eight boys with severe haemophilia A on two consecutive days using the HJHS. The boys ranged in age from 4-12 years and presented with variable joint damage. Six index joints (elbows, knees and ankles) were assessed on 11 impairment items including swelling, flexion and extension loss and gait. Concordance was measured by the intra-class correlation co-efficient. RESULTS: Reliability of the HJHS was excellent with an inter-observer co-efficient of 0.83 and a test-retest of 0.89. CONCLUSION: This study is the first in a series to assess the psychometric properties of the HJHS, a promising new measure of joint health in boys with haemophilia.

Ankle Joint↗
PubMed2006

Treadmill training for individuals with multiple sclerosis: a pilot randomised trial.

This pilot study investigated whether 4 weeks of aerobic treadmill training in individuals with multiple sclerosis (MS) improved mobility and reduced fatigue. Individuals with MS were recruited to this prospective, randomised controlled trial. Individuals were assessed at baseline, week 7 and 12 with a 10 metre timed walk, a 2 minute walk, the Rivermead Mobility Index, and the Fatigue Severity Scale. After a pre-assessment familiarisation session and a baseline assessment, individuals were randomly allocated to an initial intervention or delayed intervention group. Treadmill training consisted of 4 weeks of supervised aerobic exercise delivered weeks 3-6 in the immediate group and 8-11 in the delayed group. Of the initial 19 recruits, 16 individuals completed the study. There was a significant difference in walking endurance between the delayed and immediate groups at baseline (p<0.05). On reassessment in week 7, decreases in 10 metre walk time were found in both groups, which was significant in the immediate group (p<0.05). The 2 minute walk distance significantly increased in both groups (p<0.05). In the training group, reassessed at week 12 after training ceased, there was a return towards baseline scores. No significant changes in fatigue scores were found. This study showed that in individuals with MS, aerobic treadmill training is feasible and well tolerated. Walking speed and endurance increased following training with no increase in reported fatigue. Detraining occurred in the period following training. A larger randomised clinical trial is warranted.

Adult↗
PubMed2005

[Haemolytic anaemia and a clotting disorder as first signs of cystic fibrosis in two infants].

2 infants, a boy aged 8 weeks and a girl aged 5 months, presented with symptoms of fat-soluble vitamin deficiencies. The first infant had frequently voluminous bowel movements, anaemia and was not thriving; he had anaemia due to vitamin-E deficiency. The second infant had multiple haematomas on the trunk and legs due to a vitamin-K deficiency-related clotting disorder. The sweat test was positive in both cases, confirming the diagnosis of cystic fibrosis. The infants were treated with supplementary pancreatic enzymes and fat-soluble vitamins A, D, E and K. Cystic fibrosis rarely presents with symptoms of fat-soluble vitamin deficiency. However, in cases of unexplained haemolytic anaemia or haemorrhagic disorder due to vitamin E or K deficiencies, respectively, cystic fibrosis should be considered as a possible cause.

Anemia, Hemolytic↗
PubMed2005

[Quality of nuchal transluccency measurements: an exploratory study into their performance and evaluation].

OBJECTIVE: To investigate the quality of nuchal translucency measurements that were done as part of a randomised study into screening for Down's syndrome. DESIGN: Exploratory. METHOD: In the period May 2001-April 2003, 396 nuchal translucency measurements were done by 55 sonographers in 13 different echography centres. The sonographers were questioned in writing regarding their training and experience, the procedure and technique used, and the quality assurance. A filled-in questionnaire was received from 42 sono0 images at random from the 2710measurements (70%o) that had been made in 6 centres. These were evaluatedby 3 experts on the basis of the 5 criteria that are used by the Fetal Medicine Foundation (FMF). Each measurement was given 2 points for every criterion that was fulfilled, after which the average of the 3 scores was calculated. RESULTS: Of the 42 respondents, 88% had taken a nuchal translucency measurement course and 45% were certified by the FMF. Calipers were placed incorrectly by 50% of the respondents; 62% of the respondents mentioned the absence of an intern quality check. Concerning the quality-assessment of the nuchal translucency measurements, the assessors unanimously considered i3%o of the 30 images to be suitable for prenatal screen4ngand 43% to be unsuitable; their opinions as to the remaining images differed. The average quality mark was 4.7. CONCLUSION: Many nuchal translucency measurements did not fulfil the quality criteria that are imposed in order to make the measurement reliable as a screening test. There was a lack of quality securance in the echography centres.

Down Syndrome↗
PubMed2005

Expression of matrix metalloproteinases-2 and -9 in intestinal tissue of patients with inflammatory bowel diseases.

BACKGROUND/AIMS: Matrix metalloproteinases are major contributors in the breakdown and reconstitution of basement membranes and extracellular matrix in pathophysiological processes. We assessed the expression of matrix metalloproteinases-2 and -9 in intestinal tissue of patients with inflammatory bowel disease. PATIENTS/METHODS: Resected tissue specimens from patients with Crohn's disease or ulcerative colitis and control tissue from patients with a colorectal carcinoma were used for enzyme-linked immunosorbent assay, zymography, activity assay, reverse transcription polymerase chain reaction and immunohistochemistry to evaluate the expression of these matrix metalloproteinases. RESULTS: Matrix metalloproteinase-2 and more strongly matrix metalloproteinase-9 protein and mRNA were markedly increased in inflammatory bowel disease tissues, with the highest levels in severely inflamed tissues. Immunohistochemistry showed that matrix metalloproteinase-2 was present in the extracellular matrix of the submucosa, with a lower but more generalised expression in the severely inflamed regions. Matrix metalloproteinase-9 was most prominent in polymorphonuclear leukocytes and was increased, also in activity, in all inflammatory bowel disease tissues. An increased matrix metalloproteinase-9 expression in the extracellular matrix was observed in relation to the severity of inflammation. CONCLUSIONS: Matrix metalloproteinases-2 and -9 are enhanced in the intestinal tissue and seem to be actively involved in the inflammatory and remodelling processes in inflammatory bowel disease, without major differences between CD and UC.

Adult↗
PubMed2004

Effects of environmental and natural estrogens on vitellogenin production in hepatocytes of the brown frog (Rana temporaria).

The objective of this study was to investigate the ability of the natural estrogens and synthetic estrogens as well as the estrogen mimics to induce estrogen-receptor mediated vitellogenesis in primary hepatocytes of the brown frog (Rana temporaria). Based on EC50 values the following order was determined for the potency of the estrogens: 17beta-estradiol (EC50: 19-43 nM) approximately ethynylestradiol (EC50: 13-80 nM)>estrone (EC50: 218-241 nM)>DES (EC50: 338-3537 nM). Exposure to bisphenol A and methoxychlor concentrations up to 100 microM did not have any effect on in vitro vitellogenesis.

Animals↗
PubMed2004

A whole-genome scan for 24-hour respiration rate: a major locus at 10q26 influences respiration during sleep.

Identification of genes causing variation in daytime and nighttime respiration rates could advance our understanding of the basic molecular processes of human respiratory rhythmogenesis. This could also serve an important clinical purpose, because dysfunction of such processes has been identified as critically important in sleep disorders. We performed a sib-pair-based linkage analysis on ambulatory respiration rate, using the data from 270 sibling pairs who were genotyped at 374 markers on the autosomes, with an average distance of 9.65 cM. Uni- and multivariate variance-components-based multipoint linkage analyses were performed for respiration rate during three daytime periods (morning, afternoon, and evening) and during nighttime sleep. Evidence of linkage was found at chromosomal locations 3q27, 7p22, 10q26, and 22q12. The strongest evidence of linkage was found for respiration rate during sleep, with LOD scores of 2.36 at 3q27, 3.86 at 10q26, and 1.59 at 22q12. In a simultaneous analysis of these three loci, >50% of the variance in sleep respiration rate could be attributed to a quantitative-trait loci near marker D10S1248 at 10q. Genes in this area (GFRA1, ADORA2L, FGR2, EMX2, and HMX2) can be considered promising positional candidates for genetic association studies of respiratory control during sleep.

Adult↗
PubMed2004

Effects of polybrominated diphenyl ethers on basal and TCDD-induced ethoxyresorufin activity and cytochrome P450-1A1 expression in MCF-7, HepG2, and H4IIE cells.

Polybrominated diphenylethers (PBDEs) are used as additive flame-retardants in consumer products to reduce the chances of ignition and burning. Levels of certain PBDE congeners have been increasing in fish, wildlife, and human tissues during the last decades. Some PBDEs are lipophilic and persistent, resulting in bioaccumulation in the environment. The structural similarity of PBDEs to other polyhalogenated aromatic hydrocarbons such as PCBs, has raised concerns that PBDEs might act as agonists for the aryl hydrocarbon receptor (AhR). To study the possible AhR-mediated effects of the environmentally relevant PBDEs (BDE47, 77, 99, 100, 153, 154, 183, 209), the induction of cytochrome P450-1A1 (CYP1A1) was studied in human breast carcinoma (MCF-7), human hepatocellular carcinoma (HepG2), and rat hepatoma (H4IIE) cells. 7-Ethoxyresorufin-O-deethylase (EROD) was used as a marker for CYP1A1 activity. Cells were exposed for 72 h to various PBDE concentrations (0.01-10 microM). Positive controls were 2,3,7,8-TCDD (0.001-2.5 nM) and PCB126 (0.01-10 nM). None of these PBDEs was capable of inducing EROD activity; this was confirmed by real time RT-PCR for CYP1A1 mRNA. However, in cells exposed to PBDEs in combination with TCDD, a concentration-dependent decrease in TCDD-induced EROD activity occurred. Co-exposure of BDE153 (10 muM) and a maximally inducing concentration of TCDD (1 nM) reduced EROD activity to 49% of the maximum induction by TCDD alone. All tested PBDEs showed similar effects in each cell line, though quantitative differences were observed. The observed decrease in CYP1A1 activity was not due to PBDE-dependent catalytic inhibition of EROD activity or cytotoxicity, nor were decreased CYP1A1 mRNA levels observed. However, inhibition of luciferase induction in mouse (Hepa) and rat (H4IIE) hepatoma cells containing a stably transfected AhR-responsive luciferase reporter gene, suggests that BDE77 is a weak AhR antagonist or partial agonist.

Animals↗
PubMed2004

Some polybrominated diphenyl ether (PBDE) flame retardants with wide environmental distribution inhibit TCDD-induced EROD activity in primary cultured carp (Cyprinus carpio) hepatocytes.

Ethoxyresorufin-O-deethylase (EROD) activity, a catalytic function of the cytochrome P450 1A (CYP1A) microsomal oxygenase subfamily, is a popular biomarker for exposure to xenobiotics, polyhalogenated aromatic hydrocarbons (PHAHs) in particular. It has found wide use in aquatic pollution assessment both in vivo and in vitro. In such studies, subjects are often exposed to complex mixtures where various constituents can interfere with EROD-activity, possibly resulting in inadequate estimation of toxic hazard or biological response. The present study investigates the effects of polybrominated diphenyl ethers (PBDEs), a relatively new and increasingly detected group of environmental contaminants, on the validity of EROD activity as exposure marker in carp (Cyprinus carpio) hepatocytes. Freshly isolated hepatocytes of a genetically uniform strain of male carp were co-exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at concentrations of 0, 1, 3, 10, 30, and 100 pM, and one of the highly purified PBDE/PCB congeners (at concentrations of 0, 0.25, and 2.5 microM) or cleaned-up and untreated DE-71 samples (0, 0.1, and 1 microM). PBDEs were selected from the 209 possible congeners based on their relative abundance in environmental samples: BDE-47, BDE-99, BDE-100, and BDE-153. A tentative metabolite of BDE-47, 6OH-BDE-47, was also included. In addition, a commercial pentabrominated dipenylether mixture (DE-71) was tested for interference with EROD activity both with and without clean-up by carbon fractionating which removed possible planar contaminants. Polychlorinated biphenyl (PCB)-153, a reported inhibitor of EROD activity in flounder, was included for comparison. Cells were cultured for a total period of 8 days; exposure started at day 3 after cell isolation. After 5 days of exposure, cell pellets were frozen before EROD activity was determined. Upon exposure to TCDD, the cells responded with increased EROD activity as expected. Significant reduction of TCDD-induced EROD activity was found in the presence of BDE-47, BDE-99, and BDE-153, but not with BDE-100 and 6-hydroxylated BDE-47. Of these PBDE congeners, the most abundant congener in environmental samples, BDE-47, exhibited the strongest inhibition (down to 6% of the TCDD control value). The cleaned-up fraction of commercial penta-BDE (DE-71) mixture proved an even more potent inhibitor, resulting in reduction of EROD activity to 4% of the control values observed at 1.0 microM. BDE-47 and BDE-153 did not reduce TCDD-induced EROD activity when added shortly prior to measurement, suggesting possible interaction with TCDD at the level of CYP1A biosynthesis. PCB-153 did not show significant effects on EROD activity in carp in this study. The present results indicate that environmentally relevant PBDEs can interfere with determination of EROD activity in vitro, at levels reported earlier for PCBs. The observation that detected PBDE levels are rising, stresses the need for caution when interpreting EROD data on environmental samples.

Analysis of Variance↗
PubMed2004

Effects of natural and synthetic estrogens and various environmental contaminants on vitellogenesis in fish primary hepatocytes: comparison of bream (Abramis brama) and carp (Cyprinus carpio).

Interaction of environmental estrogens with the estrogen receptor (ER) has been shown in various fish species. Our objective was to compare the sensitivity of bream (Abramis brama) to (xeno-)estrogens with that of the carp (Cyprinus carpio), by measuring the effects of 17beta-estradiol (E2), estrone (E1), ethynylestradiol (EE2), bisphenol A (BPA), nonylphenol (NP), methoxychlor (MXCL), and halogenated aromatic hydrocarbons (HAHs) such as polychlorinated biphenyls (PCB126, PCB118), 2,3,7,8-tetrachlorodibenzo-dioxin (TCDD), and 2,3,4,7,8-pentachlorodibenzofuran (PCDF) on vitellogenesis in primary hepatocytes. Comparing the EC50 values in bream hepatocytes: EE2 (0.1-0.2 microM) < E1 (0.6-0.2 microM) < E2 (1.9 microM) with those of carp hepatocytes EE2 (0.03-0.06 microM) < E2 (0.3 microM) approximately E1 (0.2-0.3 microM) we found differences in sensitivity and ranking of the estrogenic potency of E2 and E1, indicating interspecies differences. Exposure to BPA, NP, MXCL, and HAHs did not or only weakly induce vitellogenesis. Bream hepatocytes coexposed to E2 and TCDD, PCB126 or PCDF showed a concentration-dependent inhibition of E2-induced vitellogenesis. IC50 (concentration of a compound that elicits 50% inhibition of E2-induced vitellogenesis) values determined in bream were: TCDD (0.02-0.09 nM) < PCB126 (0.35-0.1 nM) < PCDF (2.0-0.1) and in carp were: TCDD (0.01 nM) < PCB126 (0.4 nM). PCB118 showed no (anti-)estrogenic response. IC50 values and benchmark-concentration for TCDD and PCB126 in bream and carp hepatocytes were in the same range, indicating similar sensitivity to these compounds. Due to their anti-estrogenic capacity with benchmark-concentrations in the pM range TCDD, PCDF, and PCB126 may form a potential hazard for the reproductive success of fish species by inhibition of vitellogenesis.

Animals↗
PubMed2004

Effect of homocysteine-lowering treatment with folic acid plus vitamin B on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo-controlled, randomized trial.

BACKGROUND: A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine-lowering treatment with folic acid plus vitamin B(6) on markers of cerebrovascular atherosclerosis and cerebral microangiopathy. MATERIALS AND METHODS: Using 158 healthy siblings (mean age 46.0 +/- 7.6 years) of patients with premature atherosclerotic disease, we performed a randomized, placebo-controlled trial using 5 mg of folic acid plus 250 mg of vitamin B(6) daily (n = 78) or placebo medication (n = 80). Participants were followed for 2 years with magnetic resonance angiography (MRA) (carotid stenosis; carotid and/or vertebral elongation) and magnetic resonance imaging (MRI) (white matter abnormalities; cerebral atrophy). RESULTS: Seventeen (10.8%) subjects refused MRA/MRI owing to claustrophobia and were excluded. From the remaining 141 participants, 68 received vitamin and 73 received placebo medication [42 (61.8%) and 48 (65.8%) had postmethionine hyperhomocysteinaemia, respectively]. Twenty-four participants (15.2%; 10 in the treatment and 14 in the placebo group) did not complete both years of the trial. Vitamin treatment was associated with an increase in plasma folate (13-fold vs. placebo; P < 0.001) and vitamin B(6) (8.8-fold; P < 0.001). Fasting and postmethionine total homocysteine concentrations decreased 38.7% (95% CI, 27.4-50.0) and 29.1% (95% CI, 19.2-39.0) vs. placebo (all P < 0.001). During follow up six individuals in the vitamin-treated and 11 in the placebo-treated group deteriorated in their outcome measurements. Vitamin treatment, as compared with placebo, was associated with nonsignificantly improved outcomes on both MRA and MRI outcome measurements (odds ratio 0.48; 95% CI 0.17-1.41; P = 0.18 and 0.48; CI 0.14-1.60; P = 0.23, respectively). CONCLUSIONS: These results could indicate a possible favourable effect of homocysteine-lowering treatment on cerebrovascular atherosclerosis and cerebral microangiopathy among healthy siblings of patients with premature atherosclerotic disease, but larger trials are required to establish this with certainty.

Adult↗
PubMed2003

[Favorable results of conservative treatment with isosorbide dinitrate in 25 patients with fourth-degree hemorrhoids: a pilot study].

OBJECTIVE: To evaluate application of isosorbide dinitrate 1% ointment in the treatment of fourth-degree haemorrhoids. DESIGN: Prospective pilot study. METHOD: Twenty-five consecutive patients, 12 men and 13 women, with a median age of 48 years (range: 30-78), presenting in the period October 1999-December 2001 with fourth-degree haemorrhoids, were treated with isosorbide dinitrate 1% ointment. RESULTS: In 24 out of 25 patients (96%) the objective, reduction of the stangulated haemorrhoids and relief of pain, was achieved. In one patient the haemorrhoids were not reduced. This patient was cured after classic haemorrhoidectomy. Two patients interrupted the treatment because of severe headache, but after renewed instructions they continued the therapy and were cured. CONCLUSION: Isosorbide dinitrate 1% ointment gave good results in the treatment of fourth-degree haemorrhoids, with only few side effects.

Administration, Topical↗