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R Fimmers

Publications and source records attributed to R Fimmers.

At least 37 records · Page 2Linked to original sources
PubMed2001

Linkage analysis of asthma and atopy including models with genomic imprinting.

Asthma and atopy are two closely related, common complex traits in which a number of genetic and environmental factors are suspected to play a role. We have performed parametric and nonparametric multi-marker linkage analysis for the Busselton data set, which is part of problem 1 of Genetic Analysis Workshop 12. In particular, we have focused on the dichotomous trait atopy, as well as on dichotomized versions of the quantitative traits RASTI and loge slope. The lod score analysis with adequate modeling of a parent-of-origin effect, by use of the program GENEHUNTER-IMPRINTING, was a special interest. The most prominent findings are a multipoint mod score of 3.12 at D13S153 for RASTI, and a multipoint mod score of 4.32 at the same locus for atopy, both with four-penetrance imprinting models that point to a gene subject to maternal imprinting. In addition, there are marked differences between imprinting and non-imprinting mod scores. These results corroborate earlier findings of linkage between atopy and D13S153, but add the aspect of paternal gene expression. Furthermore, suggestive evidence for linkage to atopy is found near D6S291, D7S530, and D14S74. The best-fitting models for chromosome 6 and 14 may suggest that genomic imprinting takes plae at these two loci as well.

Adult↗
PubMed2001

The role of ovarian volume in an in vitro fertilization programme as assessed by 3D ultrasound.

The study was designed to investigate the role of ovarian volume, as assessed by three-dimensional (3D) sonography, in predicting conception in an in-vitro fertilization-embryo transfer (IVF-ET) programme. Transvaginal 3D sonography was performed in 152 cycles before initiation of ovarian stimulation (day 1) and on the day of oocyte retrieval. Ovarian volume showed no significant correlation with IVF outcome. On the contrary, all ovarian measurements were lower, albeit nonsignificantly, in the conception group. Fifteen patients (15/152, 9.9%) had a minimum unilateral ovarian volume of < or =3 mL (1 SD below the mean) on day 1 of the stimulation cycle. In this subgroup, the likelihood of conception was 6.7% (1/15) versus 21.9% (30/137) in patients with an initial minimum ovarian volume of >3 mL. This difference did not reach statistical significance. In both groups, cancellation rates due to poor ovarian response or lack of fertilization were similar. In conclusion, ovarian volumetry as assessed by three-dimensional ultrasound failed to predict conception in women undergoing IVF treatment.

Adult↗
PubMed2001

Paternity testing using Y-STR haplotypes: assigning a probability for paternity in cases of mutations.

In parentage testing with male children, Y-chromosomal STR evidence is gaining more and more importance. In some cases, multilocus haplotypes of related persons can differ at a single locus due to a mutation. In this work, a likelihood approach is presented for the calculation of a probability for paternity under consideration of a single mutation event on the Y-chromosome. The new methodology is applied to two case examples.

Child↗
PubMed2001

Endometrial receptivity in an in vitro fertilization program as assessed by spiral artery blood flow, endometrial thickness, endometrial volume, and uterine artery blood flow.

OBJECTIVE: To investigate the role of sonographic parameters in assessing endometrial receptivity in an in vitro fertilization (IVF) program. DESIGN: Prospective clinical study. SETTING: University setting. PATIENT(S): One hundred thirty-five patients in our IVF program, selected prospectively on the day of oocyte retrieval. INTERVENTION(S): Transvaginal ultrasound examination was performed before oocyte collection. MAIN OUTCOME MEASURE(S): Association between implantation rate and spiral artery blood flow (primary outcome measure) and between implantation rate and endometrial measurements as well as uterine artery blood flow (secondary outcome measures). RESULT(S): Overall implantation rate was 23.7% per cycle. Subendometrial blood flow was detected in 113 (83.7%) cases, with pregnancy occurring in 21.2%. Mean spiral artery pulsatility index values were 1.12 +/- 0.28 and 1.21 +/- 0.27 for nonconception and conception cycles, respectively. Nondetectable spiral artery blood flow was not associated with a lower implantation rate. Neither endometrial thickness nor endometrial volume was correlated with the likelihood of successful implantation. Minimum endometrial thickness and volume associated with pregnancy were 6.9 mm and 1.59 mL, respectively. CONCLUSION(S): Neither Doppler sonography of the spiral or uterine arteries nor measurement of the endometrial thickness or volume allowed a reliable prediction of subsequent IVF outcome.

Arteries↗
PubMed2001

Affective symptomatology in schizophrenia: a risk factor for tardive dyskinesia?

Affective symptomatology has repeatedly been suggested to confer susceptibility to tardive dyskinesia (TD). In our sample of 174 schizophrenic patients a history of depressive symptoms was not associated with the occurrence of TD, whereas manic symptomatology was significantly associated with the absence of TD. Thus, our data suggest that affective symptomatology cannot unambiguously be considered to predispose to TD.

Adult↗
PubMed2001

TP53 gene mutations, nuclear p53 accumulation, expression of Waf/p21, Bcl-2, and CD95 (APO-1/Fas) proteins are not prognostic factors in de novo glioblastoma multiforme.

Glioblastoma multiforme (WHO grade IV; GBM) is the most common primary brain tumor with a median survival of less than one year despite multimodal treatment regimens. However, a small subgroup of GBM patients has a better clinical outcome, with a small number of patients surviving several years. Apoptosis, a genetically determined program of cell suicide, may be induced as a consequence of critical DNA damage. However, due to defects in the signaling pathways, cancer cells may escape apoptosis, despite carrying irreversible DNA damage. In the present study, we have analyzed tumors of two age-matched, equally treated groups of GBM patients with different postoperative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 54), and 'long-term' for TTP of more than 12 months (n = 39) for alterations in apoptosis regulatory pathways: Mutations of the TP53 tumor suppressor gene and/or nuclear accumulation of its gene product p53, expression of Waf/p21, CD95 (Apo1/Fas), and Bcl-2. TP53 mutations were found in 12 out of 54 (22%) GBMs of short-term survivors and 8 out of 35 (23%) tumors of long-term survivors; the respective numbers for nuclear p53 protein accumulation were 12/53 (23%) and 10/37 (27%). Waf1/p21 expression was found in 13/53 (25%) tumors of short-term survivors and 9/35 (26%) GBMs of long-term survivors. The respective numbers for Bcl-2 expression were 25/42 (60%) and 22/36 (61%) and for CD95 (Apo1/Fas) expression 20/49 (41%) and 14/36 (39%) GBMs. The percentage of alterations in genes/proteins involved in the apoptotic pathway investigated here was virtually identical in the two groups of clinically different GBM patients. Thus, our data imply that none of these alterations investigated per se has a strong impact on the overall survival of GBM patients.

Adult↗
PubMed2001

The HLA-G genotype is potentially associated with idiopathic recurrent spontaneous abortion.

The causes for recurrent spontaneous abortion (RSA) remain unknown in a large proportion of the cases. Human leukocyte antigen (HLA)-G and HLA-E are expressed on invasive trophoblast cells, and are supposed to confer to materno-fetal tolerance. A total of 14 different nucleotide sequences have been described for HLA-G, including one dysfunctional null allele (HLA-G*0105N), while five different sequences have been described for HLA-E. In this study, 78 RSA couples and 52 fertile controls were typed for HLA-G and HLA-E by direct sequencing or single strand conformational polymorphism (SSCP) respectively. The overall analysis showed no significant difference in allele frequencies for either HLA-G or HLA-E between the two groups. However, HLA-G allele frequencies in women who had suffered from five or more RSA differed significantly from fertile controls (P: = 0.001), and from women who had undergone three or four RSA (P: = 0.027). Detailed analysis demonstrated a significant increase in the proportion of the HLA-G alleles *01013 and *0105N in the whole group of RSA women compared with fertile controls (P: = 0.007). When studying the prognostic value of HLA genotyping for pregnancy outcome (n = 41), 31 patients (76%) gave birth to a living child without performing immunotherapy. Seven out of 10 (70%) couples suffering from a further RSA carried the HLA-G*01013 or *0105N allele, compared with 10 out 31 (32%) couples giving birth (P: = 0.06). This study suggests that the HLA-G genotype may be a contributing factor in RSA.

Abortion, Habitual↗
PubMed2001

Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study.

The objective was to evaluate response rate, response duration, and toxicity after systemic and intraventricular chemotherapy in primary CNS lymphoma (PCNSL). From September 1995 to September 1998, 20 consecutive patients with PCNSL (median age 64, range 27 to 71 years) were enrolled in a pilot study evaluating chemotherapy without radiotherapy. A high dose methotrexate (MTX) (cycles 1, 2, 4, 5) and cytarabine (ara-C) (cycles 3, 6) based systemic therapy (including dexamethasone, vinca alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ara-C. Complete response was achieved in 11 and partial remission in two patients; in one response could not be determined. Four patients showed progressive disease and two (70, 71 years) died from treatment related complications. Observation time was 2 to 59 months (median 31.5 months). Kaplan-Meier estimate for median time to treatment failure (TTF) was 20.5 months, and for median survival 54 months. Systemic toxicity was mainly hematological. Ommaya reservoir infection occurred in four patients and acute transient MTX induced encephalopathy in two (subacute in another). Cognitive dysfunction possibly due to treatment was seen in only one patient after relapse and after a total of 12 cycles (six at relapse). In conclusion, primary chemotherapy based on high dose MTX and ara-C is highly efficient in PCNSL. Toxicity is manageable in patients younger than 70 years.

Adult↗
PubMed2001

Treatment of knee osteoarthritis with a topical non-steroidal antiinflammatory drug. Results of a randomized, double-blind, placebo-controlled study on the efficacy and safety of a 5% ibuprofen cream.

The efficacy and safety of a 5% ibuprofen cream (Dolgit cream) in primary knee osteoarthritis was assessed in this double-blind, randomized, placebo-controlled, parallel-group study with an adaptive sequential design. The background of the study was the need to confirm the efficacy of ibuprofen cream. Patients aged 40-75 years, with a visual analog scale (VAS) score of pain on motion of 40 mm, a Lequesne index score of 5-13 points, and a Kellgren and Lawrence radiographic score of grade II-III were enrolled between September 1999 and November 2000. The study medication was applied in a 10-cm strip t.i.d. for 7 days on the more painful knee. In the active group, each strip contained approximately 200 mg ibuprofen. The main outcome measure was the response rate to the treatment compared between both groups. Response was defined as a reduction of pain on motion, self-assessed on a VAS, of > or = 20 mm compared with baseline. The planned interim analysis after inclusion of 2 x 50 patients showed a response rate of 32 (64.0%) in the ibuprofen group and 15 (30.0%) in the placebo group (p = 0.000615). The study could then be terminated. All secondary endpoints, pain at rest, pain on pressure, Lequesne index and overall assessment, also confirmed the statistically significant differences between the groups. No drug-related adverse events were recorded. The study confirmed the efficacy of ibuprofen cream by demonstrating its statistically significant and clinically relevant superiority over the placebo cream in the treatment of primary knee osteoarthritis.

Administration, Topical↗
PubMed2001

Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in urological malignancies.

Several studies suggest that cellular adhesion molecules (CAM) play a role in cancer progression and metastasis. To evaluate the role of these molecules as possible tumor markers in patients with urological malignancies, we examined the serum levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular cellcular adhesion molecule-1 (VCAM-1) and E-selectin in patients with renal cell-, bladder-, prostate- and testicular cancer. Serum levels of 237 patients with urological cancers, renal cell carcinoma (n = 47), bladder cancer (n = 81), prostate cancer (n = 87) and testicular cancer (n = 22) and a group of 41 patients with benign prostate hyperplasia (BPH) as well as a 42 healthy control persons were examined for CAMs by specific ELISA tests. Serum CAM concentrations of all tumor patients were compared with controls and within the group according to T stage, N stage, tumor grade and extent of distant metastasis. Our results demonstrate that ICAM-1 and VCAM-1 serum levels are not stage dependently elevated; in contrary, they demonstrate a wide range and are highly variable throughout the different cancer types. In renal cell cancer and in bladder cancer, there is a significant difference for ICAM-1 between controls and T3 and T4 and metastatic cancers. A similar difference was found for VCAM-1, however not for E-selectin in any tumor group. Testicular cancer and prostate cancer did not demonstrate any difference in CAM serum levels between patients with tumors and controls. In metastatic renal cell-, bladder- and prostate cancer, the serum levels of ICAM-1 and VCAM-1 showed a tendency to correlate with the extent of metastatis although no statistical difference between patients with a single metastatic lesion and patients with multiple lesions could be demonstrated. The results of this study implicate a rather limited role of cellular adhesion molecules. Despite of significant ICAM-1 or VCAM-1 serum levels in some locally advanced tumors or metastatic disease, this observation does not provide enough relevant clinical information for use as tumor markers.

Adult↗
PubMed2000

Parametric and nonparametric multipoint linkage analysis with imprinting and two-locus-trait models: application to mite sensitization.

We present two extensions to linkage analysis for genetically complex traits. The first extension allows investigators to perform parametric (LOD-score) analysis of traits caused by imprinted genes-that is, of traits showing a parent-of-origin effect. By specification of two heterozygote penetrance parameters, paternal and maternal origin of the mutation can be treated differently in terms of probability of expression of the trait. Therefore, a single-disease-locus-imprinting model includes four penetrances instead of only three. In the second extension, parametric and nonparametric linkage analysis with two trait loci is formulated for a multimarker setting, optionally taking imprinting into account. We have implemented both methods into the program GENEHUNTER. The new tools, GENEHUNTER-IMPRINTING and GENEHUNTER-TWOLOCUS, were applied to human family data for sensitization to mite allergens. The data set comprises pedigrees from England, Germany, Italy, and Portugal. With single-disease-locus-imprinting MOD-score analysis, we find several regions that show at least suggestive evidence for linkage. Most prominently, a maximum LOD score of 4.76 is obtained near D8S511, for the English population, when a model that implies complete maternal imprinting is used. Parametric two-trait-locus analysis yields a maximum LOD score of 6.09 for the German population, occurring exactly at D4S430 and D18S452. The heterogeneity model specified for analysis alludes to complete maternal imprinting at both disease loci. Altogether, our results suggest that the two novel formulations of linkage analysis provide valuable tools for genetic mapping of multifactorial traits.

Allergens↗
PubMed2000

Induced corneal astigmatism using an asymmetric corneoscleral tunnel and a large-optic intraocular lens.

PURPOSE: To prospectively evaluate the induction of corneal astigmatism using an asymmetric corneoscleral tunnel incision (J-incision) to implant large-optic (7.0 mm) intraocular lenses (IOLs). SETTING: Department of Ophthalmology, University of Bonn, Germany. METHODS: Thirty-five patients had sutureless phacoemulsification with implantation of a 7.0 mm poly(methyl methacrylate) posterior chamber IOL using an inverse J-shaped asymmetric tunnel incision. The corneal astigmatism was measured by corneal keratometry and topography preoperatively and 1 day and 1 and 3 months postoperatively. Induced astigmatism was calculated by vector analysis. RESULTS: Mean induced changes in the corneal radii measured by keratometry were 0.17 mm +/- 0.14 (SD) on the first postoperative day, 0.18 +/- 0.14 mm after 1 month, and 0.17 +/- 0.14 mm after 3 months. Mean postoperative induced astigmatism measured by corneal topography was 1.08 +/- 0.66 diopters (D), 0.89 +/- 0.78 D, and 0.85 +/- 0.70 D, respectively. No signs of wound instability were detected. CONCLUSION: An asymmetric corneoscleral incision was suitable for implantation of large-optic IOLs, resulting in immediate stability of the induced cylindrical power in the central 3.0 mm zone as measured by keratometry. A reduction in induced corneal astigmatism can be achieved using this technique versus using symmetrical wound constructions and large-optic IOLs.

Aged↗
PubMed2000

Fetal weight estimation by three-dimensional ultrasound.

OBJECTIVE: To assess the value of three-dimensional volume scanning in predicting fetal weight at birth. STUDY DESIGN: Prospective cross-sectional study within 7 days of delivery. A total of 190 patients were considered for final analysis (formula-finding group: n = 125, formula evaluation group: n = 65). Inclusion criteria were a singleton pregnancy and absence of chromosomal or significant structural anomalies. Three-dimensional (3D) volumetric measurements of the fetal thigh, upper arm and abdomen were performed together with conventional two-dimensional (2D) biometry. RESULTS: All measurements were completed successfully in each patient. Polynomial regression analysis with standard biometric parameters and volumes of the upper arm, the thigh and the abdomen was employed to yield the best-fit formula for prediction of fetal weight at birth. The new 3D formula (estimated fetal weight (EFW) = -1478.557 + 7.242 x thigh volume + 13.309 x upper arm volume + 852.998 x log10 abdominal volume + 0.526 x BPD3) proved to be superior to established 2D equations with the lowest mean error (25.8 +/- 194.4 g), the lowest mean absolute error (155.2 +/- 118.2 g) and the lowest mean absolute percentage error (6.1 +/- 5.0%) when studied prospectively in the evaluation group. CONCLUSION: 3D sonography allows superior fetal weight estimation by including soft tissue volume. Further studies at the extremes of fetal weight are needed to confirm the value of our formula in these subsets.

Adult↗
PubMed2000

The size of the fetal thoracolumbar spine: a three-dimensional ultrasound study.

OBJECTIVE: To evaluate three-dimensional sonographic measurements of the thoracolumbar spine in the 16-37 week fetus. DESIGN: Prospective cross-sectional study. SUBJECTS: Two hundred and eighty-nine patients between 16 and 37 weeks of gestation were enrolled at the time of their anomaly scan or routine third trimester scan if fetal size was appropriate for gestational age and if no fetal anomalies were apparent. METHODS: Three-dimensional (3D) volume calculation of the first and fifth lumbar vertebral body, the 12th thoracic vertebral body and the whole lumbar spine was performed in the transverse plane of the multiplanar mode while lumbar spine length was determined in the sagittal plane. RESULTS: All volumetric measurements were significantly correlated with gestational age and estimated fetal weight. For each examined parameter regression analysis was performed to describe the 'best-fit' equation. CONCLUSIONS: 3D sonography allows volume calculation of the fetal spine. Our study provides further data relating to volume changes in the developing fetal spine between 16 and 37 weeks of gestation.

Cross-Sectional Studies↗
PubMed2000

Evidence for major histocompatibility complex-mediated effects on spermatogenesis in humans.

Studies in fertile and infertile populations suggest an influence of genes of the major histocompatibility complex (MHC) on reproduction, although it remains unresolved if MHC-mediated effects on fertility are based on direct immunological or non-immunological effects of human leukocyte antigen (HLA) genes or rather on defects in MHC-associated non-HLA genes which affect gamete quality and embryonic development. We analysed allele frequencies for HLA class II loci DQA1, DQB1 and DRB1 and HLA class II haplotype frequencies in couples with tubal and andrological infertility who were treated with assisted reproductive techniques. Males with severe andrological infertility had significantly different allele frequencies for all three HLA loci when compared to males with normozoospermia, whereas no difference was found in the females. Differences in allele frequencies were stronger when only males whose partners achieved pregnancies after assisted reproduction treatment were compared. In those subgroups, we could also observe significant differences in three locus HLA class II haplotype frequencies. In summary, patients with male factor infertility differ in their HLA class II allele constitution from males with normozoospermia, which suggests that genes identical to or located in close vicinity to HLA class II genes may influence spermatogenesis and male gamete function.

Alleles↗
PubMed2000

Quantitative assessment of subendometrial blood flow by three-dimensional-ultrasound is an important predictive factor of implantation in an in-vitro fertilization programme.

This study was designed to investigate the role of three-dimensional (3D) power Doppler sonography of the (sub-) endometrial area on the first day of ovarian stimulation in predicting the outcome of an in-vitro fertilization (IVF) programme. Among the 75 cycles analysed, the overall pregnancy rate was 20% (15/75) per cycle and 23.8% (15/63) per embryo transfer. Intra-observer variability of the colour histogram was checked in 14 patients with the results demonstrating a high level of agreement. Neither endometrial measurements nor uterine blood flow were correlated with the pregnancy rate. In contrast, all 3D indices were significantly lower in conception compared with non-conception cycles (P < 0.05). Logistic regression analysis found the subendometrial flow index to be the strongest predictive factor of IVF success among the tested sonographic parameters (P = 0.04). In conclusion, quantitative assessment of spiral artery blood flow may be of predictive value for implantation in IVF cycles even before ovarian stimulation therapy is started.

Adult↗
PubMed2000

Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors.

Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2, and PTEN genes were analyzed in addition. Our data point to several novel genetic loci associated with brain tumor development, demonstrate relationships between molecular changes and histopathological features, and further expand the concept of molecular tumor variants in neuro-oncology. This catalogue may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors.

Alleles↗