[Prevalence of the use of psychoactive medication to treat young persons with autism spectrum disorder in the province of Antwerp, Belgium]. / Gebruik van psychoactieve medicatie bij kinderen en jongeren met autisme-spectrumstoornis in de provincie Antwerpen.

BACKGROUND: Very little information is available concerning the prevalence of the use of medication for treatment of individuals with autism spectrum disorder (ASD), particularly in European countries. Earlier studies have shown that a large number of patients with ASD use at least one psychoactive drug and that the numbers are increasing. Even in the nineties, studies suggested that the frequent use of psychoactive medication was widespread, although at the time there were only limited grounds for this assumption. AIM: To assess the prevalence with which psychoactive medication and complementary and alternative medicine (CAM) are being used for treating young people with ASD, and also to investigate relations between medication use and a number of individual characteristics that are included in the Behavioral Model of Health Service Use. METHOD: The study sample (0-17 years) in the province of Antwerp, Belgium, was recruited by various means. We used a questionnaire that had been previously used in North American studies and that had to be completed by the parents of the young persons involved in the study. RESULTS: We included data from 263 questionnaires. In our sample 42.6% of the young persons used one or more one psychoactive drug. More than 12.2% used more than one drug. The most frequently used psychoactive drugs were ADHD-medication (31.6%) and antipsychotics (16.7%). About 14% used at least one CAM. We found a positive relationship between the use of medication and psychiatric comorbidity and/or epilepsy, the severity of autism and the parents' living conditions. CONCLUSION: We found a relatively low use of antipsychotics, antidepressants, mood stabilisers and sedatives, the prevalence being lower that that reported in North American studies. Our findings appear to be in accordance with current clinical guidelines.

[Autism spectrum disorder and substance use disorder: an unknown comorbidity?]. / Autismespectrumstoornis en verslaving: een onbekende comorbiditeit?

We describe the diagnosis and treatment of a patient with autism spectrum disorder (ASD) and substance use disorder (SUD). The patient had been given the dual diagnosis of Asperger's disorder and SUD. On that basis the approach adopted and the treatment provided seemed appropriate. Little is known about the comorbidity of ASD and SUD and it has hardly been reported in the scientific literature or in clinical practice. Epidemiological research shows that this dual diagnosis occurs in clinical populations. A careful psychiatric diagnosis is important in order to ensure that the comorbidity is recognised at an early stage and treated in an appropriate manner.

Digital pressure and flow measurement upon local cooling in Raynaud's disease. Effect of naftidrofuryl.

Two local cold provocation tests were carried out in 25 healthy volunteers and in 14 patients with Raynaud's disease, using finger systolic pressure (FSP) and digital blood flow measurements. Mean FSP was significantly lower in Raynaud's patients compared to healthy volunteers at 15 degrees C and 10 degrees C (cuff temperature). Maximal digital flow (at skin temperature of 38 degrees C) was slightly though not significantly lower in Raynaud's patients as compared to normals (27 +/- 3 versus 36 +/- 4 ml/100 ml/min). Upon cooling, statistical significance was reached starting from finger skin temperature of 24 degrees C. Overlap between the two groups was considerable but only 1 out of 13 patients with Raynaud's disease had both tests normal. Ten of the patients participated in a double-blind cross-over trial with naftidrofuryl (200 mg t.i.d.) versus placebo. Significant (p less than 0.05) subjective improvement was noted after 6 weeks with naftidrofuryl but this was not necessarily substantiated by an increased digital flow or pressure in the test situation.

Anaplastic nodules in an ovarian mucinous tumor. Case report and literature review.

The case of a 38-year-old woman with an ovarian mucinous cyst that contained solid nodules of anaplastic carcinoma is described. Hitherto, only 17 cases of this aggressive type of ovarian tumor have been reported. The patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy and a para-aortic and pelvic lymphadenectomy. The tumor was classified as FIGO Stage Ic. On flow cytometry the tumor was DNA diploid. Also, on image analysis the regions with well- differentiated carcinoma and the regions with anaplastic nodules were DNA diploid. No adjuvant treatment was given. There is no evidence of disease 30 months after diagnosis.

Placebo-controlled, double-blind, two-centre trial of ketanserin in intermittent claudication.

The effects of ketanserin, a serotonin antagonist, were studied in 37 patients with intermittent claudication in a double-blind placebo-controlled, trial done in London and Leuven. 40 mg ketanserin taken orally three times a day for 4 months was associated with a clear-cut inhibition of serotonin-induced platelet aggregation but no changes were observed in pain-free and maximum walking distance on a treadmill, in ankle/arm Doppler systolic blood pressure ratio, or in reactive hyperaemia after 3 min of ischaemia. In contrast, the placebo group had increases in both pain-free and maximum walking distance (p less than 0.05).

Ticlopidine in the treatment of intermittent claudication: a 21-month double-blind trial.

After a 3-month, single-blind, run-in period, 151 patients with intermittent claudication were randomly allocated to receive the antiplatelet agent ticlopidine (250 mg twice per day) or an identical placebo. One hundred and twenty patients completed the double-blind phase of the trial, which lasted 21 months. The primary analysis was performed according to the "intention-to-treat principle" in all 151 enrolled patients. There was, continuing on from the third month after randomization, a progressive and sustained improvement of the pain-free and maximum walking distances in the two treatment groups that was significantly greater in the ticlopidine group. The ankle-arm systolic blood pressure ratio at rest and after exercise increased in a significant manner in the ticlopidine group only. In a secondary analysis, with exclusion of 25 patients because of protocol violations at selection, consistently significant differences in favor of the ticlopidine group were still observed for maximum walking distance and systolic ankle-arm blood pressure ratio, both at rest and after exercise. No major side effects were reported in the treated group. It is concluded that long-term treatment with ticlopidine improves walking ability and ankle systolic blood pressure in patients with claudication.

Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia.

The liver is a highly vascularized organ which frequently hosts metastases in patients with colorectal adenocarcinomas. The hypothesis of this study is that the hypoxic drive of angiogenesis might be minimal or absent in those growing liver metastases which are capable of preserving the stromal structure, including the numerous sinusoidal blood vessels. Representative paraffin sections of liver metastases from 26 patients with colorectal adenocarcinoma were investigated. Three different growth patterns were found. In the desmoplastic and in the pushing growth patterns (42% and 46% of all metastases, respectively), the architecture of the liver parenchyma was not preserved. In the replacement growth pattern (12% of all cases), the reticulin pattern of the liver parenchyma was conserved within the metastases at the tumour-liver parenchyma interface. The endothelial cells of the blood vessels near the interface in the metastases of the replacement type did not express CD34, nor were they surrounded by alpha-smooth muscle actin-positive mural cells. In the desmoplastic and in the pushing growth patterns, 23% and 52% of all blood vessels in this area were covered by pericytes. The fraction of proliferating endothelial cells was low in the metastases with a desmoplastic or a replacement growth pattern (about 3%), compared with metastases with a pushing growth pattern (11%). Tumour cell apoptosis was highest in the pushing-type metastases and was inversely correlated with microvessel density in liver metastases. The ratio of the proliferating tumour cell fraction and the proliferating endothelial cell fraction, roughly representing the degree of angiogenesis-dependent growth, was three- to four-fold higher in the replacement-type metastases compared with the other metastases. In summary, the present study has demonstrated that liver metastases are a heterogeneous group, with different growth patterns which predict the fraction of immature blood vessels, the fraction of proliferating endothelial cells, and the fraction of apoptotic tumour cells. The replacement growth pattern expands with minimal angiogenesis by co-opting the stroma with the sinusoidal blood vessels of the liver.

Evidence for genetic heterogeneity in inflammatory bowel disease (IBD); HLA genes in the predisposition to suffer from ulcerative colitis (UC) and Crohn's disease (CD).

Family and epidemiological studies support a genetic susceptibility to UC and CD. Conflicting reports regarding associations between UC and HLA-DR2 and between CD and various HLA alleles have been published. The aim of this study was to determine whether molecularly defined HLA-DR genes are associated with these diseases in a Dutch group of patients. Fifty-nine unrelated Dutch UC patients and 89 CD patients were typed using DNA-based methods. A total of 2400 healthy local blood donors served as controls. The phenotype frequency of the HLA-DRB1*15 allele was increased in UC patients compared with controls (42% versus 26% in controls; P = 0.006; odds ratio (OR) = 2.1), and was predominantly found in female patients (53% versus 24%; P = 0.001; OR = 3.5). The DRB1*15 allele was increased in UC patients having a positive family history (P = 0.01; OR = 5.8). Among the 16 patients who showed an increase in extent of disease during follow up, 10 were DRB1*15+ (P = 0.002; OR = 4.8). The frequency of the DRB1*13 allele was decreased in patients with UC (15% versus 28% in controls; P = 0.04; OR = 0.5). In CD, no association was observed between disease or particular clinical subgroups and any allele tested. The present study provides additional evidence for the genetic association between UC and HLA-DRB1*15, and supports recent findings that the susceptibility gene(s) for CD is not located in the HLA class II region.

Genetic markers in clinically well defined patients with ulcerative colitis (UC).

Results of genetic association studies in UC are conflicting. We propose that the power of candidate gene studies will increase when disease heterogeneity is taken into account. Phenotype frequencies of molecularly defined HLA-DR alleles, polymorphisms in the tumour necrosis factor-alpha (TNF-alpha), lymphotoxin-alpha (LT-alpha), IL-1 receptor antagonist (IL-1Ra) and IL-1beta genes were determined in 98 clinically well characterized UC patients with a mean period of follow up of 10 years, and ethnically matched healthy controls (HC). The alleles HLA-DRB1*0103 (phenotype frequency 6% versus 0.2%; P = 0.0002; odds ratio (OR) 27.6) and DRB1*15 (41% versus 26%; P = 0. 001; OR = 2.0, compared with HC) were associated with overall disease susceptibility. Subgroup analysis revealed that DRB1*15 was only increased in females (53% versus 24%; P < 0.0001; OR = 3.5), but not in males. With regard to disease localization, all DRB1*0103+ patients had extensive disease (P < 0.002; OR = 33.5), and DRB1*15 was found in 59% of females with extensive colitis (P < 0.0001; OR = 4.4). DRB1*0103 was significantly increased in patients undergoing colectomy (P < 0.0002; OR = 84). No association between overall disease susceptibility and the cytokine gene polymorphisms were found. Subgroup analysis revealed several significant associations, but most did not retain significance when corrected for multiple comparisons. However, a noticeable finding was that haplotype TNF-C was significantly associated with progression in extent of disease (P = 0.003, OR = 20.4). This study provides additional evidence for the role of DRB1 alleles in the susceptibility to UC, and supports the hypothesis that these alleles may determine the severity of the disease. The cytokine gene polymorphisms evaluated in this study do not seem to be strong risk factors for the overall disease susceptibility in UC, but may be involved in determining the severity of the disease.