University Nijmegen Medical Centre Research Articles

Are myo-inositol, glucose and zinc concentrations in amniotic fluid of fetuses with spina bifida different from controls?

Associations are reported between myo-inositol, glucose, zinc and the occurrence of spina bifida. To gain more insight into the pathogenesis of spina bifida, the concentrations of myo-inositol, glucose and zinc were determined in amniotic fluids from pregnancies with a spina bifida or unaffected control fetus. Amniotic fluids of 27 pregnancies complicated by spina bifida and 49 controls were collected at the Department of Obstetrics and Gynecology of the University Medical Center Nijmegen in the Netherlands. Myo-inositol, glucose and zinc concentrations were determined. By indication, the samples were taken at different gestational ages. Therefore, the data were evaluated using multiple linear regression analysis to adjust for gestational age. Amniocentesis was performed at a more advanced gestational age in the spina bifida group than in controls. In the spina bifida group, amniotic fluid myo-inositol, glucose and zinc concentrations gradually declined throughout pregnancy. At a gestational age of 15 weeks, the estimated mean amniotic fluid glucose and zinc concentrations in the spina bifida group were, respectively, significantly lower (p< or =0.5) and higher (p< or =0.5) compared with the control group. At the same gestational age, the estimated mean myo-inositol concentrations were comparable in both groups. At a gestational age of 38 weeks, the estimated mean myo-inositol, glucose and zinc concentrations were not significantly different in the spina bifida compared with the control group. This study may suggest that a derangement in zinc and glucose transfer or metabolism is associated with spina bifida. Since compounds in amniotic fluid are only a very crude marker of the actual fetal condition, studies that focus on the metabolism of these compounds on tissue or even cellular level should be performed to clarify their role in the pathogenesis and future prevention of spina bifida.

Dental maturity in children with a complete bilateral cleft lip and palate.

Dental age in children with a bilateral cleft lip and palate (BCLP) was assessed and compared with children without cleft. Dental age was estimated for 74 children with a complete BCLP (54 boys and 20 girls) from 364 orthopantomograms. Nonlinear regression curves were made between 5 and 14 years of age for boys and girls separately. A comparison was made with a sample of Dutch children (91 girls and 90 boys) without oral clefts for three different age groups, namely 5, 9.5, and 14 years of age. Data collection was carried out at the Cleft Palate Center, University Medical Center Nijmegen (The Netherlands). A sample from the Nijmegen Growth Study was used as a normative sample. At 5 years of age, boys with a BCLP were significantly delayed in dental age compared to boys without cleft. After that age, no significant differences in dental age were found. For girls with a BCLP, no difference in dental age with the girls without cleft could be found. Dental age in BCLP showed a tendency to be delayed at 5 years of age. At the ages of 9.5 and 14 years of age, no differences were found. Further investigation on the development of individual teeth is suggested to gain more insight into the origin of this delay.

Dental Maturity in Children With a Complete Bilateral Cleft Lip and Palate

Abstract Objective: Dental age in children with a bilateral cleft lip and palate (BCLP) was assessed and compared with children without cleft. Design: Dental age was estimated for 74 children with a complete BCLP (54 boys and 20 girls) from 364 orthopantomograms. Nonlinear regression curves were made between 5 and 14 years of age for boys and girls separately. A comparison was made with a sample of Dutch children (91 girls and 90 boys) without oral clefts for three different age groups, namely 5, 9.5, and 14 years of age. Setting: Data collection was carried out at the Cleft Palate Center, University Medical Center Nijmegen (The Netherlands). A sample from the Nijmegen Growth Study was used as a normative sample. Results: At 5 years of age, boys with a BCLP were significantly delayed in dental age compared to boys without cleft. After that age, no significant differences in dental age were found. For girls with a BCLP, no difference in dental age with the girls without cleft could be found. Conclusion: De...

Preconception Care: A Screening Tool for Health Assessment and Risk Detection

Background. Identification of risk factors for adverse pregnancy outcome is a main component of preconception care, but requires adequate time and knowledge. This study compares self-administered questionnaires to history taking by a physician to evaluate the reliability of such a screening tool for prepregnancy risk detection.Methods. One hundred ninety-three women from the outpatient clinic of Obstetrics and Gynecology of the University Medical Center Nijmegen, The Netherlands, were included in a study on preconception care. A Preconceptional Health Assessment form with risk variables pertaining to social, nutritional, medical, infectious disease, medication, reproductive and family history, and two Family History surveys (for the woman and her partner) were completed by 186 couples at home. A physician then orally verified the written answers. Agreement between the written and the oral answers was calculated using kappa statistic.Results. An excellent agreement level was found for all sections of the Preconceptional Health Assessment form (overall κ = 0.88) except for nutritional history (κ = 0.70). The Family History surveys also showed a high agreement level (κ = 0.92 for women and κ = 0.90 for men).Conclusions. The questionnaires are an accurate screening tool for preconceptional risk factors. We advocate their implementation in various settings to facilitate the provision of preconception care.

Alcohol Dehydrogenase Type 3 (ADH3) and the Risk of Bladder Cancer

Objectives: The polymorphic enzyme alcohol dehydrogenase (ADH) catalyses the conversion of ethanol into the carcinogenic metabolite acetaldehyde which is partly excreted into the urine. Objectives of this pilot study are to determine whether this polymorphism may be related to bladder cancer and whether it modifies the relation between alcohol intake and bladder cancer. Methods: 120 bladder cancer patients and 133 convenience controls were recruited at the University Medical Centre Nijmegen. A self–administered questionnaire was used to assess alcohol intake and potential confounders. DNA was isolated from peripheral blood, and ADH3 genotype was determined using PCR/RFLP. People with the ADH3 genotype γ1γ1 were compared to people with other ADH3 genotypes. Above moderate drinkers (>14 glasses of alcohol per week) were compared to moderate drinkers. Odds ratios (ORs) and 95% confidence intervals were computed using logistic regression analyses. Results: After correction for sex, age and smoking, ORs for ADH3 genotype and alcohol intake were 2.10 (1.05–4.22) and 1.21 (0.60–2.44), respectively. Moderate drinkers with the ‘high–risk’ (γ1γ1) ADH3 genotype appeared to have a threefold higher risk of bladder cancer compared to moderate drinkers with a ‘low–risk’ (γ1γ2 or γ2γ2) genotype. Surprisingly, the ORs for above moderate drinkers with the low–risk genotype (1.95; 95% CI: 0.85–4.48) and with the high–risk genotype (2.18; 95% CI: 0.82–5.77) were almost similar, suggesting no interaction. Conclusions: ADH3 genotype is a possible risk factor for bladder cancer. Although moderate drinkers with the γ1γ1 genotype seem to have the highest risk, we did not get a clear indication that ADH3 genotype modifies the relationship between alcohol intake and bladder cancer.

Defecation problems in children with Hirschsprung's disease: a prospective controlled study of a multidisciplinary behavioural treatment

Constipation, faecal incontinence, soiling and difficult toilet training remain significant problems in children with Hirschsprung's disease after corrective surgery. Chronic defecation problems can have various negative implications. At the University Medical Centre Nijmegen, a multidisciplinary behavioural treatment was developed to treat defecation problems. In this paper, a prospective controlled study is presented concerning the effect of this treatment upon children suffering from chronic defecation problems following corrective surgery for Hirschsprung's disease. The effect of treatment was studied in 27 children (21M, 6F, mean age 5.2 y, range 2–11 y). Fourteen children were allocated to the experimental treatment group. The 13 children allocated to the waiting‐list control group were also treated following a waiting period of 6 mo. On all outcome variables, children in the experimental treatment group had significantly better results after treatment than children in the waiting‐list control group after the waiting period. No effect of age upon treatment was found. The effect of treatment remained significant on all outcome variables at a mean follow‐up of 7 mo after the end of treatment. Conclusion: Multidisciplinary behavioural treatment is successful in decreasing chronic defecation problems in children with Hirschsprung's disease.

Cancer incidence in relatives of patients with testicular cancer in the eastern part of The Netherlands

Objectives. To investigate the incidence of malignant tumors in first-degree relatives of patients with testicular cancer. Methods. Information about the occurrence of cancer in relatives of patients treated for testicular germ cell cancer (TC) at the Department of Urology of the University Medical Centre Nijmegen from 1986 to 1997 was collected using postal questionnaires from 379 (72%) of 524 patients. The expected numbers of cancers in relatives were computed from age- and sex-specific incidence data in the Netherlands Cancer Registry. The observed/expected (O/E) ratios with 95% confidence intervals (CIs) were calculated using Byar’s approximation of the exact Poisson test. Results. The O/E ratio for developing cancer in the families of patients with TC was 1.2 (95% CI 1.0 to 1.3). Among first-degree relatives of patients with TC, more TC was observed than expected (O/E 3.3; 95% CI 1.4 to 6.9). The risk for brothers of patients with TC increased 5.9-fold (95% CI 2.2 to 12.8). Both the risk of developing lung cancer (O/E 1.5) and malignancy of the female genital tract in sisters (O/E 2.8) was slightly increased. In contrast, the risk of urinary tract malignancies (O/E 0.3) and other and unknown primary tumors (O/E 0.2) had a lower incidence among relatives. However, both the increased and decreased risk of nontesticular cancer for first-degree relatives may have been caused by misclassification. Conclusions. TC clusters in families were more pronounced among brothers than among fathers and sons. This study supports previous reports that families of patients with TC do not seem to be prone to nontesticular cancer. Additional investigations in families with TC are recommended to map candidate genes for TC.

The relationship between disease activity, joint destruction, and functional capacity over the course of rheumatoid arthritis.

To investigate the relationship between functional capacity, disease activity, and joint destruction over the course of rheumatoid arthritis (RA). The followup data on 378 patients with early RA (duration <1 year), included in an open, prospective study since 1985 at the Department of Rheumatology of the University Medical Center Nijmegen, were used. Functional capacity, disease activity, and joint destruction were assessed using the Health Assessment Questionnaire disability index (HAQ DI), the Disease Activity Score (DAS), and a modification of the sharp radiographic damage score, respectively. Multiple linear regression was used to model the data collected at 0, 3, 6, and 9 years after study start, to investigate which variables influenced functional capacity during the disease course. A general linear mixed model for longitudinal data, which included the variables identified as significant in the multiple linear regression models and several interaction terms between the variables, was run. On average, the functional capacity of the patients, as measured by the HAQ DI, worsened over the course of the disease after an initial improvement. After an initial reduction in the extent of disease activity, the mean DAS remained more or less stable over the course of the disease. The mean modified sharp joint damage score worsened over the course of the disease, with a slower progression rate later in the disease. In the multiple linear regression at 0, 3, and 6 years after study start, disease activity was found to be an important factor influencing functional capacity, and at 6 and 9 years, joint damage had an important effect on functional capacity. Furthermore, at 6 and 9 years, there was an interaction effect of joint destruction with disease activity. In the general linear mixed model, disease activity, joint damage, and an interaction effect of disease activity and joint damage were the main factors explaining functional capacity. The effect of disease activity and joint destruction on functional capacity changes over the course of the disease. In early RA, functional capacity is most associated with disease activity, and in late disease, with joint damage.

Psychological Impact of Preconception Counseling: Assessment of Anxiety before and during Pregnancy

Objective: Assessment of anxiety levels in women and men before and after preconception counseling and during the first trimester of pregnancy. Methods: Couples were recruited from the fertility clinic of the University Medical Center Nijmegen, the Netherlands. Anxiety was assessed using the 40-item Spielberger State-Trait Anxiety Inventory (STAI). Results: 53 women and 51 men (74%) completed the STAI both before and after counseling. Anxiety levels did not change significantly after counseling or during the first trimester of pregnancy. 83.4% would recommend preconception counseling to others. Conclusion: Preconception counseling is valued by the majority of women and men and does not lead to adverse psychological effects.