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Biomedical subjects

R Fimmers

Publications and source records attributed to R Fimmers.

At least 55 records · Page 3Linked to original sources

Qualitative determination of urinary human complement factor H-related protein (hcfHrp) in patients with bladder cancer, healthy controls, and patients with benign urologic disease.

OBJECTIVES: To assess the diagnostic quality of human complement factor H-related protein (hcfHrp, BTA STAT(TM)) as a qualitative urinary marker for bladder cancer. METHODS: Urine samples of 354 individuals (76 healthy volunteers, 111 patients with benign urologic disorders, 167 patients with histologically proven bladder cancer) were examined prior to therapy for the presence of hcfHrp. RESULTS: Overall test sensitivity was 62.9%. Sensitivity of low-grade/low-stage tumors was <50% and was thus comparable to published sensitivities of urinary cytology. In high-stage, high-grade tumors sensitivity was 100 and 77.3%, respectively. Superficial tumors with high risk of progression (pT1G3) were detected significantly better (88.9% sensitivity) than low-risk superficial tumors (pTa G1-3/pT1G1-2; 48.2%; p < 0.001). The overall specificity (healthy individuals and patients with benign urologic disease) was 93.0%. CONCLUSION: Since test sensitivity is comparable to urinary cytology and specificity is excellent, hcfHrp should be further evaluated in prospective studies focussing on the follow-up of patients with bladder cancer.

Adolescent↗

Usefulness of conventional blood groups, DNA-minisatellites, and short tandem repeat polymorphisms in paternity testing: a comparison.

A total of 215 paternity cases were analysed after testing 24 marker systems. Despite technical advantages of polymerase chain reaction related polymorphisms (automatisation, employment of robots, lesser requirements concerning of quality and quantity of DNA) it could be shown that the exclusive employment of a parentage testing kit is compromised by an increased risk of erroneous conclusions. It is estimated that in about 3-4% of the cases ambiguous situations have to be expected which are caused by the occurrence of single or double exclusions. In these cases it is impossible to decide whether the exclusions indicate either true nonpaternity or a de novo mutation. The situation might become even more complicated if an involvement of a close relative of the alleged father cannot be ruled out. We cautiously advance the hypothesis that in parentage testing DNA minisatellite polymorphisms from an optimal set of tools.

Blood Grouping and Crossmatching↗

Linkage analysis with adequate modeling of a parent-of-origin effect.

We present an extension to parametric linkage analysis that allows modeling diseases with a parent-of-origin effect (i.e., imprinting). Different penetrances are assumed for individuals being heterozygous at the disease locus, depending on their having inherited the disease allele from the father or mother. Motivated by the finding of a maternally expressed locus influencing alcohol consumption in mice (Alcp2), the analysis method has been included into the program GENEHUNTER for application to Problem 1, Collaborative Study on the Genetics of Alcoholism of Genetic Analysis Workshop 11. By this extension, a powerful tool is provided for adequately modeling an inherited disease in linkage analysis that supposedly has imprinting effects. The program has been used to analyze the data set on alcohol dependence in humans and can be applied to other genetically determined traits as well.

Alcoholism↗

The fetal spinal canal--a three-dimensional study.

The size of the lumbar spinal canal was evaluated in a prospective cross-sectional ultrasound (US) study to determine normal size values for lumbar part of the vertebral canal. A total of 88 patients undergoing routine obstetric US were studied between 16-41 weeks gestation. Structural anomalies or growth restriction were excluded. Area and volume of the vertebral canal in L1, L3 and L5 were calculated by three-dimensional (3-D) US. The size of the spinal canal correlated well with gestational age and no major differences could be found between upper and lower lumbar spine. By 3-D US, in vivo assessment of the spinal canal becomes possible. Further studies are needed to confirm our findings.

Cross-Sectional Studies↗

Vascular endothelial growth factor (VEGF) in astrocytic gliomas--a prognostic factor?

Survival in astrocytic gliomas is closely related to WHO tumor grade. Within one tumor grade, especially in grade II and III tumors, the clinical course is variable and can hardly be predicted by histological criteria. Neovascularization is a neuropathological hallmark in high grade gliomas and angiogenic factors may play an important role in malignant tumor progression. Therefore, 162 primary astrocytic gliomas (57 astrocytomas WHO grade II, 27 astrocytomas WHO grade III and 78 glioblastomas WHO grade IV) were investigated immunohistochemically for expression of vascular endothelial growth factor (VEGF), which is considered to represent the main angiogenic factor in astrocytic gliomas. Clinical data known to influence prognosis were documented. VEGF expression was found in 21 of 57 astrocytomas WHO grade II (36.8%), in 18 of 27 astrocytomas WHO grade III (66.7%) and in 50 of 78 glioblastomas (64.1%). A strong correlation between VEGF expression and survival was found within the whole study group, however, within one tumor grade no such correlation was obvious. In a multifactorial analysis VEGF expression was not found to be an independent prognostic factor in astrocytic gliomas.

Adult↗

Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families.

Previously reported linkage of bipolar affective disorder to DNA markers on chromosome 18 was reexamined in a large sample of German bipolar families. Twenty-three short tandem repeat markers were investigated in 57 families containing 103 individuals with bipolar I disorder (BPI), 26 with bipolar II disorder (BPII), nine with schizoaffective disorder of the bipolar type (SA/BP), and 38 individuals with recurrent unipolar depression (UPR). Evidence for linkage was tested with parametric and non-parametric methods under two definitions of the affected phenotype. Analysis of all 57 families revealed no robust evidence for linkage. Following previous reports we performed separate analyses after subdividing the families with respect to the sex of the transmitting parent. Fourteen families were classified as paternal and 12 families as maternal. In 31 families the parental lineage of transmission of the disease could not be determined ('either' families). Evidence for linkage was obtained for chromosomal region 18p11.2 in the paternal families and for 18q22-23 in the 'either' families. The findings on 18p11.2 and 18q22-23 support prior evidence for susceptibility loci in these regions. The parent-of-origin effect on 18p11.2 is confirmed in our sample. The delineation of characteristics of 'either' families requires further study.

Bipolar Disorder↗

Fetal lumbar spine volumetry by three-dimensional ultrasound.

OBJECTIVES: To evaluate three-dimensional sonographic volume measurements of the thoracolumbar spine from 16 to 25 weeks of gestation in the normally developing fetus. DESIGN: Prospective cross-sectional study. SUBJECTS: The study included 103 women between 16 and 25 weeks of gestation. They were enrolled at the time of their anomaly scan. None of the pregnancies was associated with structural anomalies and in each case fetal size was deemed appropriate for gestational age. METHODS: Three-dimensional volume calculation of the 1st and 5th lumbar vertebral body, the 12th thoracic vertebral body and the whole lumbar spine was performed, using the perpendicular frontal, sagittal and transverse planes. The lumbar spine length was determined. RESULTS: A statistically significant increase in all measurements was found with advancing gestational age. CONCLUSIONS: Three-dimensional ultrasonography allows volume calculation of the fetal spine. Our study provides preliminary data about volume changes in the developing fetal spine between 16 and 25 weeks' gestation.

Adolescent↗

[Can 3D volumetric analysis of the fetal upper arm and thigh improve conventional 2D weight estimates?].

AIM: To determine the usefulness of three-dimensional ultrasound volumetry of fetal thigh and upper arm in predicting weight at delivery. METHOD: Inclusion criteria to our prospective study were single-ton pregnancies with a planned or expected delivery within 96 hours of enrollment. In 74 patients (formula-finding group) standard fetal biometry, followed by measurement of thigh and upper arm volumes by three-dimensional ultrasound, was performed. Subsequently, our new 3D-formulas were tested in a prospective validation group of 52 patients. RESULTS: Both upper arm and thigh volumes correlated well with birth weight (r2 = 0.95, respectively, p < 0.0001). The best result, however, was achieved by a combination of standard 2D-measurements with the volumetric data of upper arm and thigh (r2 = 0.98, p < 0.0001). With use of polynomial regression analysis we obtained two best-fit formulas: BIRTH WEIGHT: -263.8 +13.7269 x Arm Volume +7.16575 x Thigh Volume +148.2 x ATD. Birth weight: -1288.7 +51.9502 x Arm Volume -0.252 x Arm Volume 2 -2.1766 x Thigh Volume +0.0321 x Thigh Volume 2 +36.2509 x GA -0.7526 x GA2 +654.3 x BIP -36.6136 x BIP2 -381.8 x ATD +24.0927 x ATD2. CONCLUSION: Three-dimensional volumetry of the fetal thigh and upper arm may improve prediction of birth weight. Further larger studies are needed to validate our results.

Arm↗

Three-dimensional endometrial volume calculation and pregnancy rate in an in-vitro fertilization programme.

This study was designed to investigate the role of three-dimensional (3D) endometrial ultrasound in predicting the outcome of an in-vitro fertilization (IVF) programme. In 47 IVF cycles measurements of endometrial thickness and volume, as assessed by 3D transvaginal ultrasound on the day of oocyte retrieval, and concentrations of oestradiol and progesterone in the same patient sampled on the day of sonography, were related to the occurrence of a successful implantation. The overall pregnancy rate was 31.9% (15/47). Fifteen pregnant patients had a mean endometrial thickness and volume of 10. 8 +/- 2.3 mm (mean +/- SD) and 4.9 +/- 2.2 ml, respectively. Thirty-two non-pregnant patients had corresponding measurements of 11.8 +/- 3.4 mm and 5.8 +/- 3.4 ml respectively. Endometrial thickness varied widely in both groups, in pregnant patients from 6. 9 to 16.0 mm, in non-pregnant patients from 6.5 to 21.1 mm. Oestradiol concentrations were not significantly correlated with either endometrial thickness or volume. The conclusion from the present data is that 3D volume estimation of the endometrium as well as analysis of endometrial thickness on the day of oocyte retrieval had no predictive value for conception in IVF cycles.

Adult↗

Molecular genetic analysis as a tool for evaluating stereotactic biopsies of glioma specimens.

Over the last years, distinct genetic lesions have been associated with individual tumor entities. Stereotactic biopsy has become an essential diagnostic tool in surgical neuro-oncology. In order to evaluate the potential of molecular analyses in stereotactic biopsies, we examined a series of 156 human brain tumors from patients undergoing stereotactic biopsy for molecular alterations typically seen in astrocytic gliomas and compared those results with a control group of 268 astrocytic tumors obtained at open surgery. Stereotactic biopsies of astrocytomas with borderline histopathological features between the WHO grades II and III showed a higher rate of allelic losses on chromosome 10 than those of the WHO grade II from open surgery (p = 0.011). Stereotactic biopsies of astrocytomas with borderline histopathological features between the WHO grades III and IV showed a higher rate of allelic losses on chromosome 10 than those of the WHO grade III from open surgery (p = 0.013). This indicates that stereotactic biopsies with features intermediate between grades are likely to correspond to the higher malignancy grade. Our data demonstrate that molecular genetic approaches can be successfully applied to stereotactic glioma biopsies. The difference in the distribution of malignancy associated genetic alterations between a stereotactic and openly resected group of gliomas indicates that histopathology may underestimate the malignant potential in some stereotactic specimens. We propose to further evaluate the molecular analysis of stereotactic glioma biopsies as a useful adjunct to standard histopathological procedures.

Biopsy↗

Comparison of membrane filtration methods for the recovery of legionellae from naturally contaminated domestic drinking water supplies.

We compared four methods for the cultural recovery of legionellae from naturally contaminated water samples: (A) inoculating 1 and 0.1 ml directly on the selective solid growth medium, (B) filtration through cellulose nitrate membrane filters and inoculating the resuspended residue corresponding to 100 and 10 ml of the original sample on the medium, (C) filtration through polycarbonate filters and inoculating the resuspended residue corresponding to 100 and 10 ml of the original sample, and (D) filtration of 100 and 10 ml through cellulose nitrate filters and incubating the filter directly on the medium. Of the water samples tested in parallel, 103 samples tested positive for legionellae in at least two of these methods. The mean number of CFU/ml recovered by methods A, B, C, and D werte 5.45, 1.85, 1.70, and 2.26, respectively. The differences between the methods proved to be highly significant except for methods B and C (p = 0.112), the results of which correlated closely with each other (r = +0.96). In comparison with method A the recovery rates of methods B, C, and D were found to be 60, 57, and 69%, respectively. We recommend the use of method A for the recovery of legionellae at concentrations of > or = 1 CFU/ml. If legionellae below this concentration are to be detected we recommend method D as the easiest and most sensitive technique.

Collodion↗

Expression of the ATM gene is significantly reduced in sporadic breast carcinomas.

The gene mutated in ataxia telangiectasia (A-T) patients (ATM) is located on chromosome 11q22-23, a region frequently altered in mammary tumors. Patients homozygous for ATM mutations are prone to develop a variety of different neoplasms. Female heterozygotes have been reported to carry a 5- to 8-fold increased risk of breast cancer. However, germline mutations in the ATM gene are rare in women with sporadic breast carcinomas. Most of the alterations described in A-T patients result in a functionally inactive ATM protein. Moreover, it has been suggested that mutations of the ATM gene in A-T patients influence the amount of ATM mRNA and that this may affect the severity of the disease. In the present study, we have analyzed ATM transcripts in a series of 39 breast carcinomas, 14 benign breast lesions and 12 normal breast tissue samples. ATM mRNA levels were determined by semiquantitative competitive RT-PCR. Competitor RNA molecules for the ATM gene and the housekeeping gene beta-2-microglobulin (B2M) were generated by PCR mutagenesis. Low concentrations of ATM transcripts were detected in breast carcinomas, intermediate levels in benign lesions and highest levels in normal breast tissue specimens (F-test, p = 0.0013). Our results indicate that reduced expression of the ATM gene may contribute to the development and/or malignant progression of breast carcinomas.

Ataxia Telangiectasia Mutated Proteins↗

D3S1358: sequence analysis and gene frequency in a German population.

Eight alleles of the STR system D3S1358 were observed and sequenced. The alleles ranged in size from 119 bp (13 repeats) to 147 bp (20 repeats) and consist of two diverse tetranucleotides: [AGAT] and [AGAC]. Alleles 16 and 17 show basic repeats which are different in one base. The allele frequency of 499 unrelated persons from SW-Germany yielded no deviation from Hardy-Weinberg equilibrium. A comparison with a Portuguese population showed some small differences, i.e. one allele has not been found in the Portuguese sample until now. The mutation rate was estimated with 0.8% analysing 65 families.

Alleles↗

Prospective evaluation of shoulder-related problems in patients with pectoral cardioverter-defibrillator implantation.

BACKGROUND: The pectoral approach to implantation of cardioverter defibrillators (ICDs) has become a standard in defibrillator therapy because of reduced generator size, weight, and volume. But the size of these devices is still comparable to the size of the early conventional antibradycardia pacemakers that were associated with a number of significant pocket- and shoulder-related problems after implantation in the pectoral region. In a prospective, single-center study of 50 patients with subpectoral implantation of a fourth-generation ICD, the ipsilateral shoulder joint was evaluated regarding active shoulder motility, shoulder-related pain, shoulder function, shoulder elevation, insertion tendinitis, and morphologic alterations of the shoulder. METHODS AND RESULTS: The shoulder was evaluated before implantation and at 3, 6, and 12 months after implantation. Shoulder motility was documented by evaluating active abduction, forward flexion, and external rotation. Shoulder-related pain and function were documented by the "Basic Shoulder Evaluation Form," insertion tendinitis was diagnosed by standardized palpation and the impingement test, and morphologic alterations were documented by ultrasound and radiograph of the shoulder. Three months after implantation, 20 (40%) patients had a reduced active abduction, 30 (60%) patients had an impaired active forward flexion, and eight (16%) patients had a reduced external rotation. Thirty-one (62%) patients reported shoulder-related pain or impaired shoulder function according to the "Basic Shoulder Evaluation Form." Twenty-four (48%) patients showed a shoulder elevation and 21 (42%) patients demonstrated clinical signs of insertion tendinitis. After 12 months the number of patients with reduced active abduction, forward flexion, and external rotation dropped to four (8%). Shoulder-related pain and reduced function were documented in seven (13%) patients, four (8%) patients still had shoulder elevation, and five (10%) patients still had signs of insertion tendinitis. None of the postoperatively performed ultrasounds or radiographs showed any pathologic shoulder alterations. No predictors for the occurrence of shoulder-associated problems could be found. CONCLUSIONS: (1) Decreased active shoulder motility, shoulder-related pain, reduced function, shoulder elevation, and insertion tendinitis of the ipsilateral shoulder joint are diagnosed in many patients 3 months after subpectoral ICD implantation. (2) After 12 months the number of patients with impaired shoulder motility, function, shoulder-related pain, shoulder elevation, and insertion tendinitis decreased significantly. (3) Ultrasound and radiographs of the ipsilateral shoulder showed no evidence of pathologic morphologic alterations after subpectoral ICD implantation. (4) No shoulder-associated problems required an operative revision of the subpectoral generator pocket.

Defibrillators, Implantable↗

[Evaluation of the effects of bioadhesive substances as addition to oral contrast media: an experimental study].

PURPOSE: To evaluate the additional effect of bioadhesives in combination with iotrolan and barium as oral contrast media in an animal model. METHOD: The bioadhesives Noveon, CMC, Tylose and Carbopol 934 were added to iotrolan and barium. The solutions were administered to rabbits by a feeding tube. The animals were investigated by computed tomography (CT) and radiography after 0.5, 4, 12, 24 and in part after 48 hours. Mucosal coating and contrast filling of the bowel were evaluated. RESULTS: Addition of bioadhesives to oral contrast media effected long-term contrast in the small intestine and colon, but no improvement in continuous filling and coating of the gastrointestinal tract was detected. Mucosal coating was seen only in short regions of the caecum and small intestine. In CT the best results for coating were observed with tylose and CMC, in radiography additionally with carbopol and noveon. All contrast medium were well tolerated. CONCLUSION: The evaluated contrast medium solutions with bioadhesives have shown long-term contrast but no improvement in coating in comparison to conventional oral contrast media.

Acrylic Resins↗

Redifferentiation therapy-induced radioiodine uptake in thyroid cancer.

UNLABELLED: Due to a dedifferentiation of tumor cells, some thyroid carcinomas lose their capability for radioiodine (RI) concentration. This phenomenon is associated with a worse prognosis and prevents effective treatment. Retinoic acid (RA) is known to induce redifferentiation in various kinds of tumors and has been used recently in thyroid cancer. METHODS: Twelve patients (9 women, 3 men) with 6 papillary, 4 follicular and 2 mixed-cell type tumors (including 4 Hurthle cell carcinomas) were treated orally with RA (dose: 1.18 +/- 0.37 mg/kg body weight) for at least 2 mo before RI therapy. None of the patients could be treated with any other modality (RI, surgery, external radiation) when RA administration was started. Initially, clinically important tumor sites did not take up significant amounts of RI. Changes of RI uptake and thyroglobulin (Tg) serum values were determined. Glucose metabolism was followed with fluorodeoxyglucose (FDG) PET imaging in 10 patients before and in 5 patients after RA treatment. RESULTS: In 2 patients, a significant RI uptake was induced by RA, and in another 3 patients a faint RI uptake was achieved (responder group). In 7 patients, no change of RI uptake was observed (nonresponder group). Median Tg was increased from 105-840 microg/liter during RA therapy in the responder group, which was significantly higher than the nonresponder group (173-134 microg/liter). FDG PET was positive in all 10 patients before RA therapy. PET showed variable patterns of changes (increase/decrease/disappearance) in glucose consumption related to RA response. CONCLUSION: RA can induce RI uptake in some patients with RI negative thyroid carcinoma tumor sites. Response to RA is associated with a significantly higher increase of Tg, suggesting that a restoration of Tg synthesis can be addressed as a redifferentiation parameter in these patients.

Adenocarcinoma, Follicular↗

Genomic deletions in the BRCA1, BRCA2 and TP53 regions associate with low expression of the estrogen receptor in sporadic breast carcinoma.

Sporadic breast carcinoma is associated with multiple genetic alterations. The clinical relevance of these alterations, however, needs further clarification. In the present study we analyzed 266 spontaneously arising breast carcinomas for allelic losses in the BRCA1 and TP53 regions on chromosome 17, the BRCA2 region on chromosome 13, the ATM (mutated in ataxia-telangiectasia) region on chromosome 11 and on the chromosomal arms 7q and 16q. In addition the following clinical and pathological parameters were evaluated: age at diagnosis, tumor size, presence or absence of regional and distant metastases, hormone-receptor status, histopathological classification and tumor grading. The analysis of genetic and clinical observations revealed significant associations: absence of expression of the estrogen receptor was linked to a high rate of allelic losses of markers in the BRCA1, TP53 and BRCA2 regions. Expression of the progesterone receptor coincided with allelic loss on the long arm of chromosome 16. High-grade malignant lesions and ductal differentiation were frequently associated with allelic losses in the proximal portion of chromosome 17q. The accumulation of multiple allelic deletions was linked to high-grade malignant tumors, to tumor size, and to loss of expression of the estrogen receptor. Our data point to a relationship between clinically relevant prognostic factors and specific genomic deletions in the BRCA1, BRCA2 and TP53 region.

Breast Neoplasms↗

Efficacy and side-effects of clozapine not associated with variation in the 5-HT2C receptor.

In the present study we tested the hypothesis that individual response to clozapine treatment and/or the occurrence of side-effects may be influenced by genetic variation in the serotonin 5-HT2C receptor. We investigated the frequency of a common Cys23Ser substitution, which is known to alter the pharmacological properties of the protein, in 152 patients treated with clozapine. Presence of the Ser23 variant was previously reported to predict a good response to clozapine. However, our results did not support an association between genetic variation of the 5-HT2C receptor and response to clozapine. This held true whether the patients were subgrouped for sex and length of treatment. Moreover, we found no consistent association with any of the observed side-effects.

Adult↗