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Biomedical subjects

H van den Berg

Publications and source records attributed to H van den Berg.

At least 19 recordsLinked to original sources

Effect of fortified spread on homocysteine concentration in apparently healthy volunteers.

OBJECTIVE: To determine the effect of folic acid, vitamin B(6) and B(12) fortified spreads on the blood concentrations of these vitamins and homocysteine. DESIGN AND SETTING: A 6-week randomized, double-blinded, placebo-controlled, parallel trial carried out in a clinical research center. SUBJECTS: One hundred and fifty healthy volunteers (50% males). INTERVENTIONS: For 6 weeks, the subjects consumed the test spreads (20 g/day): containing per 20 g (1) 200 microg folic acid, 2 microg vitamin B(12) and 1 mg vitamin B(6), or (2) 400 microg folic acid, 2 microg vitamin B(12) and 1 mg vitamin B(6) or (3) no B-vitamins (control spread). RESULTS: The B-vitamin status increased on using the test spreads, with the largest effect on the serum folate concentration: 48% in men and 58% in women on spread 1 and 92 and 146%, respectively, on spread 2 (P-values all <0.05). The plasma homocysteine decreased in the groups treated with the fortified spreads as compared to the control group. Average decreases were for males: 0.7+/-1.5 micromol/l (6.8%) on spread 1 and 1.7+/-1.7 micromol/l (17.6%) on spread 2 and for females: 1.4+/-1.2 micromol/l (14.2%) and 2.4+/-2.0 micromol/l (23.3%), respectively (P-values all <0.05). CONCLUSIONS: Consumption of a spread fortified with folic acid, vitamin B(6) and vitamin B(12) for 6 weeks significantly increases the blood concentrations of these vitamins and significantly decreases the plasma concentration of homocysteine. Fortified staple foods like spreads can contribute to the lowering of homocysteine concentrations.

Adolescent↗

Risk of second malignancies in long-term survivors of childhood cancer.

INTRODUCTION: Childhood cancer survivors are known to be at increased risk for second malignancies. PATIENTS AND METHODS: The risk of second malignancies was assessed in 1368 5-year survivors of childhood cancer treated in the Emma Children's Hospital AMC in Amsterdam. The median follow-up time was 16.8 years. RESULTS: Sixty two malignancies were observed against 5.4 expected, yielding a standardised incidence ratio (SIR) of 11.2 (95% confidence interval: 8.53-14.4; absolute excess risk: 3.2 per 1000 person-years). New observations were the strongly increased risks of meningiomas (SIR=40) and basal cell carcinomas (SIR=9). Patients whose treatment involved radiotherapy had a 2-fold increased second cancer risk compared to patients with chemotherapy alone. DISCUSSION: The relative risk of second malignancies does not decrease till at least 30 years of follow-up. With aging of the survivor cohort this results in a strong increase of the AER, due to the rising background risk of cancer with age.

Adolescent↗

Parental desire and acceptability of spermatogonial stem cell cryopreservation in boys with cancer.

BACKGROUND: In the near future, a substantial proportion of adults will be childhood cancer survivors. The cryopreservation and transplantation of spermatogonial stem cells (SSCs) is currently successful in animals; application in humans seems likely in the near future. Cryopreserving SSCs might become an important issue in childhood cancer. Because this might require testicular biopsies or hemicastration, parental desire/acceptability for SSC collection was enquired for. METHODS: Three hundred eighteen parents of boys surviving at least 2 years after the diagnosis of cancer were asked about collecting SSCs by biopsy or hemicastration and collecting sperm by masturbation or electrostimulation. Opinions were assessed as if at the time of diagnosis and at the present time. RESULTS: Sixty-three per cent of parents responded. At diagnosis, SSC collection by means of biopsy was approved by 61%, hemicastration by 33% and collecting sperm by 70% (P < 0.013). The acceptability of performing hemicastration was significantly lower than all other forms of SSC/sperm collection. No differences were observed between parents' present opinion and opinion at diagnosis. No differences related to treatment intensity, presumed negative fertility effects and pubertal state were found. CONCLUSIONS: Infertility is a major topic for parents. For prepubertal boys, the collection of SSCs might be a great relief in respect of the fertility issue. Collecting SSCs by biopsy is desired and accepted by the majority of parents; hemicastration is accepted by one-third of parents. The translation of SSC cryopreservation and transplantation from animal models to humans is eagerly awaited.

Adolescent↗

Calcitonin therapy in central giant cell granuloma of the jaw: a randomized double-blind placebo-controlled study.

The successful therapeutic use of calcitonin in patients with a central giant cell granuloma has been shown in several case reports. In a prospective, randomized, double-blinded, placebo-controlled clinical trial, 14 patients with a histologically confirmed central giant cell granuloma and normal calcium and parathyroid hormone serum levels were studied over 2 years. Patients were treated with intranasally administered salmon calcitonin (200 IU/day) or a placebo once a day. The placebo-controlled period was 3 months, after which all patients were treated with calcitonin for 1 year. Treatment response was assessed at the end of the placebo-controlled study phase (3 months), at the end of therapy (15 months' timepoint with patients being on calcitonin treatment for either 12 or 15 months) and at 6 months' follow-up. The chi(2)-test was used to compare the proportion of patients with a tumour reduction >/=10% of the pretreatment measurement between the 2 populations at the 3 timepoints: no differences were observed between the placebo group and the calcitonin group. At the 6-month follow-up timepoint, tumour volume had decreased by >/=10% in a total of 7 patients with a 37.9% (95% CI 31.3-44.5%) mean volume reduction in this subgroup. Complete remission was not observed.

Adolescent↗

Limited regression of central giant cell granuloma by interferon alpha after failed calcitonin therapy: a report of 2 cases.

Central giant cell granuloma (CGCG) is a benign lesion of the jaws with a sometimes locally aggressive behaviour. The most common therapy is surgical curettage which has a high recurrence rate, especially in lesions with aggressive signs and symptoms (i.e. pain, paresthesia, root-resorption and rapid growth). Alternative therapies such as interferon alpha (INFalpha) or calcitonin are described in the literature. In this study 2 patients with an aggressive CGCG are presented who were treated with INF mono-therapy. INF mono-therapy was capable of terminating the rapid growth of the lesion in both patients and induced a partial reduction. Total resolution, however, was not obtained and alternative treatment is still necessary.

Adolescent↗

Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans.

OBJECTIVE: The aim of this study was to investigate whether milk fortified with folic acid enhances the folate status of humans and whether the presence of folate-binding proteins (FBP) in pasteurised milk affects the bioavailability of folic acid from fortified milk. In untreated and pasteurised milk, folate occurs bound to FBP, while FBP is (partly) denatured in ultra-high-temperature (UHT)-treated milk. The effect of FBP on folate bioavailability is still unclear. DESIGN, SUBJECTS AND SETTING: Healthy, free-living subjects (n=69) aged 18-49 y participated in a 4-week double-blind, placebo-controlled dietary intervention study. INTERVENTION: In addition to a fully controlled diet, the subjects consumed each day 500 ml of pasteurised or UHT milk, either fortified or not with 200 mug folic acid. RESULTS: Consumption of fortified milk increased folate concentrations in serum and in red blood cells (RBC) by 6.6-7.0 nmol/l (P<0.001) and 32-36 nmol/l (P<0.01), respectively. Similarly, plasma homocysteine concentrations were lowered 0.88-0.89 micromol/l (P=0.001) in subjects who consumed fortified milk. The bioavailability of folic acid from pasteurised milk relative to that of folic acid from UHT milk was 74-94% (NS), depending on the parameter used. CONCLUSIONS: Milk fortified to supply an additional 200 microg of folic acid/s substantially increased folate status, and decreased plasma total homocysteine concentrations in young, healthy subjects. Milk is therefore a suitable matrix for fortification to enhance the folate status in humans. No significant effect of endogenous FBP was found on the bioavailability of folic acid from milk.

Adolescent↗

Decreasing the number of MOPP courses reduces gonadal damage in survivors of childhood Hodgkin disease.

BACKGROUND: Children treated for Hodgkin disease are at risk for gonadal damage. Since most children were treated with radiotherapy (RT) in combination with chemotherapy, the presumed detrimental effect of MOPP (mustine, vincristine, procarbazine, and prednisone) (in contrast to schemes with less or without alkylating agents) could not be discerned completely from the effects of RT. PROCEDURES: Children with Hodgkins disease treated without RT were included in sequential protocols containing six courses of MOPP (n = 24), six courses of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (n = 17), or three courses of MOPP/ABVD (n = 35). Of these 76 patients, 48, who had completed treatment and had reached puberty, were investigated for gonadal damage. RESULTS: Of the male patients, 81% of MOPP treated patients had increased follicular stimulating hormone (FSH) values, in 23% luteinizing hormone (LH) values were abnormal. In ABVD treated patients, no elevated levels of FSH or LH were noted. In 30% of patients treated with MOPP/ABVD, FSH values were abnormal, but no abnormal LH values were found. Median testicular volume per group decreased in relation to a higher number of MOPP courses. Sperm analysis revealed azoospermia in nearly all MOPP treated patients. In ABVD and MOPP/ABVD treated patients both oligospermia and azoospermia were noted. The number of sperm samples were too less to make any sound conclusions. Menarche occurred in all females, however in some at a relatively later age. One female patient treated with MOPP/ABVD had a normal pregnancy. CONCLUSIONS: Limitation of MOPP therapy to three courses, in children treated without any RT, results in less gonadal damage as compared with six MOPP courses. From our data, MOPP damages Sertoli cells and may also damage Leydig cells as suggested by the higher LH values in conjunction with normal testosterone levels.

Adolescent↗

[Nutrition and health--vitamins and vitamin supplements].

A balanced diet based on the Guidelines of the Netherlands Nutrition Centre provides a suitable basis for the maintenance of good health. However, there are a number of situations where supplementation with vitamins is clearly indicated. These include infants (vitamin A, D and K), young children, and pregnant and lactating women (vitamin D), future expectant mothers (folic acid) and the elderly (vitamin D). If doubts exist about a sufficient vitamin intake via the regular diet, a daily supplement supplying all vitamins at the level of the recommended daily allowance (RDA) is considered to be a responsible and safe choice. Epidemiological research indicates that the incidence of certain diseases is lower if the intake of vitamins is significantly higher than the RDA. However to date, targeted intervention studies have provided little unequivocal evidence to support this argument. For certain vitamins (A, D, folic acid, B6, nicotinic acid and beta-carotene) excessive intakes are associated with a health risk or clear toxicity. In the case of vitamin B6, nicotinic acid, folic acid and beta-carotene this risk is mainly limited to the use of high-dose supplements.

Age Factors↗

Pan-European multicentre economic evaluation of recombinant urate oxidase (rasburicase) in prevention and treatment of hyperuricaemia and tumour lysis syndrome in haematological cancer patients.

GOALS: Hyperuricaemia (HU) and tumour lysis syndrome (TLS) are complications of acute myeloid/lymphoid leukaemia (AML/ALL) and non-Hodgkin lymphoma (NHL) leading to increased morbidity and mortality. The objective was to assess incremental cost-effectiveness ratios (ICER) of preventing/treating HU and TLS with recombinant urate oxidase, rasburicase (Fasturtec/Elitek). PATIENTS AND METHODS: Incidence and costs of HU and TLS were based on a multi-country chart review. Life expectancy at the time of diagnosis was based on published survival rates and age at diagnosis. Reductions of HU/TLS following treatment with rasburicase were based on clinical trial data. RESULTS: Prevention with rasburicase appears highly cost-effective in children (ICER between Eur 425 and Eur 3054 per life-year saved, LYS). In adults, prevention is more cost-effective in NHL and ALL (maximum ICER of Eur 41383 and Eur 32126 per LYS). Treatment of established HU/TLS with rasburicase is cost-saving in children and highly cost-effective in adults. The results are robust in children. In adults, the prevention strategy appears sensitive to the risk of HU/TLS. CONCLUSIONS: In conclusion, rasburicase, in addition to the demonstrated clinical benefit, is an economically attractive new option in the treatment of HU, both in adults and children. In prevention the drug has an attractive economic profile in children, and is cost-effective in adults with ALL and NHL.

Adult↗

Mechanistic and anti-proliferative studies of two novel, biologically active bis-benzimidazoles.

We have previously synthesised a number of novel head-to-head bis-benzimidazole derivatives that are structurally related to the fluorochrome, Hoechst 33258, and which possess strong affinity for A:T sites in the minor groove of duplex DNA. Initial studies revealed these compounds to exhibit potent antiproliferative activity against a range of ovarian cell lines and to inhibit transcription in an in vitro setting. In this study, we have examined their cellular behaviour in detail and have shown that two of these compounds (ABA13 and ABA833) potently inhibit the proliferation of a range of human tumour cell lines, and show some specificity towards breast carcinoma cell lines. In most of the cell lines investigated, ABA833 was the more potent of the two compounds. Flow cytometric analysis revealed that ABA13 and ABA833 (50-500 nM) induced an S phase block and increased the pre-G1 population in MCF-7 and MDA 468 human breast cancer cells. An increase in the pre-G1 population of RKO colon carcinoma cells was seen only at 500 nM with ABA833, reflecting the reduced sensitivity of this cell line to the bis-benzimidazoles in comparison to the breast cancer cell lines. Mechanistic studies revealed that neither ABA13 or ABA833 act as topoisomerase I (topo I) or topoisomerase II (topo II) poisons in plasmid or kinetoplast DNA (kDNA) relaxation assays, but both compounds do inhibit the catalytic activity of these enzymes. Drug uptake studies showed that reduced sensitivity of MCF-7adr and RKO cells compared with MCF-7 to both ABA13 and ABA833 correlated with a markedly reduced intracellular drug accumulation.

Antineoplastic Agents↗

[Nephrotic syndrome as a paraneoplastic symptom of Hodgkin's disease in two children].

A 13-year-old girl and a 3-year-old boy presented with the clinical symptoms of nephrotic syndrome. Both patients developed a nodular mass in the cervical region, which appeared to be due to Hodgkin's disease. The renal disease was a paraneoplastic phenomenon of Hodgkin's disease. Chemotherapy given for Hodgkin's disease also cured the nephrotic syndrome. A few years later one of the patients experienced a recurrent episode of nephrotic syndrome in conjunction with a recurrence of Hodgkin's disease but this was once again treated successfully. Nephrotic syndrome is a known but rare paraneoplastic syndrome accompanying Hodgkin's disease. It is thought that T cell dysfunction leads to a secretion of cytokines which alters the permeability of the glomerular basement membrane. This dysfunction is not only apparent during the period of active disease and this could clarify why paraneoplastic syndrome can exist or recur outside the period in which the malignancy is overt. The clear recognition of a paraneoplastic syndrome is important, as it is often only necessary to treat the malignancy.

Adolescent↗

The TEL-AML1 real-time quantitative polymerase chain reaction (PCR) might replace the antigen receptor-based genomic PCR in clinical minimal residual disease studies in children with acute lymphoblastic leukaemia.

Prospective studies in children with B-precursor acute lymphoblastic leukaemia (ALL) have shown that polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) using immunoglobin (Ig) and T-cell receptor (TCR) gene rearrangements as targets can be used to identify patients with a high relapse risk. The disadvantage of this approach is that for each patient preferably two different targets have to be identified. The t(12;21)(p13;q22) with the TEL-AML1 fusion gene is present in approximately 25% of children with B-precursor ALL. In these patients, sensitive reverse transcription (RT)-PCR analysis of the TEL-AML1 fusion transcript might be a more simple and less laborious alternative approach. However, it is unknown how stable the mRNA is and whether the number of transcripts per leukaemic cell remains constant during follow-up. We investigated whether the MRD results obtained using RT-PCR of TEL-AML1 transcripts correlated with the clinically validated genomic PCR for Ig and TCR gene rearrangements. Therefore, we used real-time quantitative (RQ)-PCR analysis for both types of targets and assessed the MRD levels in 36 follow-up bone marrow samples (obtained during the first 1.5 years after diagnosis) from 13 patients with B-precursor ALL. In 34/36 bone marrow samples the Ig/TCR RQ-PCR and TEL-AML1 RQ-PCR revealed equal levels of MRD and these results had a strong correlation (P < 0.0001, R2 = 0.84). Therefore, we conclude that the TEL-AML1 RQ-PCR can, in principle, replace Ig/TCR RQ-PCR in B-precursor ALL with t(12;21).

Child↗

[Juvenile xanthogranuloma: a form of histiocytosis with an excellent prognosis].

In three patients, a girl aged six weeks and two boys aged eight and three months, juvenile xanthogranuloma was diagnosed. This is a rare cutaneous disorder that predominantly occurs during infancy and early childhood. It is one of the non-malignant, non-Langerhans cell histiocytoses (class II histiocytoses). It is characterized by a circumscript, firm, yellow-brown and sometimes pink-red nodule or papule located mainly on the face or scalp. Diagnosis can be made on the clinical appearance. However, this may need to be confirmed by a histopathological investigation, which includes immunohistochemical stains. In contrast to generalized histiocytoses, the prognosis of juvenile xanthogranuloma is excellent: the cutaneous tumour disappears spontaneously in one to six years. However, extracutaneous involvement, which is most frequently located in the eye, can occur. Moreover, juvenile xanthogranuloma is associated with neurofibromatosis type I and juvenile chronic myeloid leukaemia. This rare but possibly life-threatening systemic involvement justifies meticulous follow-up.

Diagnosis, Differential↗

Identification of four new translocations involving FGFR1 in myeloid disorders.

The 8p11 myeloproliferative syndrome (EMS) is associated with three translocations, t(8;13)(p11;q12), t(8;9)(p11;q33), and t(6;8)(q27;p11), that fuse unrelated genes (ZNF198, CEP110, and FOP, respectively) to the entire tyrosine kinase domain of FGFR1. In all cases thus far examined (n = 10), the t(8;13) results in an identical mRNA fusion between ZNF198 exon 17 and FGFR1 exon 9. To determine if consistent fusions are also seen in the variant translocations, we performed RT-PCR on four cases and sequenced the products. For two patients with a t(8;9), we found that CEP110 exon 15 was fused to FGFR1 exon 9. For two patients with a t(6;8), we found that FOP exon 5 (n = 1) or exon 7 (n = 1) was fused to FGFR1 exon 9. To determine if FGFR1 might be involved in other myeloid disorders with translocations of 8p, we developed a two-color FISH assay using two differentially labeled PAC clones that flank FGFR1. Disruption of this gene was indicated in a patient with a t(8;17)(p11;q25) and Ph-negative chronic myeloid leukemia in association with systemic malignant mast cell disease, a patient with acute myeloid leukemia with a t(8;11)(p11;p15), and two cases with T-cell lymphoma, myeloproliferative disorder, and marrow eosinophilia with a t(8;12)(p11;q15) and ins(12;8)(p11;p11p21), respectively. For the patient with the t(8;11), the chromosome 11 breakpoint was determined to be in the vicinity of NUP98. We conclude that 1) all mRNA fusions in EMS result in splicing to FGFR1 exon 9 but breakpoints in FOP are variable, 2) two-color FISH can identify patients with EMS, and 3) the t(8;17)(p11;q25), t(8;11)(p11;p15), t(8;12)(p11;q15), and ins(12;8)(p11;p11p21) are novel karyotypic changes that most likely involve FGFR1.

Chromosomes, Human, Pair 11↗

Reduction of irradiated small bowel volume and accurate patient positioning by use of a bellyboard device in pelvic radiotherapy of gynecological cancer patients.

PURPOSE: To reduce the volume of small bowel within pelvic treatment fields for gynecological cancer using a bellyboard device and to determine the accuracy of the prone treatment position. MATERIALS AND METHODS: Fifteen consecutive patients with a gynecologic malignancy who were treated with postoperative pelvic radiotherapy were selected for this study. The volume of small bowel within the treatment fields was calculated for both the supine and prone treatment positions. The patients were treated in the prone position in a so-called bellyboard device. During treatment sessions electronic portal images were obtained. An off-line setup verification and correction protocol was used and the setup accuracy of the positioning in the bellyboard was determined. RESULTS: The average volume of small bowel within the treatment fields was 229 cm(3) and 66 cm(3) in the supine and prone treatment, respectively, which means an average volume reduction in the prone position of 64% (95% CI 56-72%), as compared with the supine position. For the position of the patient in the field, the systematic error defined by the standard deviation (SD) of the mean difference per patient between simulation and treatment images was 1.7 mm in the lateral direction, 2.1 mm in the craniocaudal direction and 1.7 mm in the ventrodorsal direction. On average, only 0.4 setup correction per patient was required to achieve this accuracy. The random day-to-day variations were 1.9 (1SD), 2.6 and 2.3 mm, respectively. Standard deviations of the systematic differences between patient positioning relative to the bellyboard were 6.2 mm in lateral direction and 9.1 mm in craniocaudal direction. CONCLUSIONS: Treatment of gynecological cancer patients in the prone position using a bellyboard reduces the volume of irradiated small bowel. An off-line verification and correction protocol ensures accurate patient positioning. Daily setup variations using the bellyboard were small (1 SD<3 mm). Therefore for pelvic radiotherapy in patients with a gynecological malignancy, the use of a bellyboard is recommended.

Aged↗