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R Fimmers

Publications and source records attributed to R Fimmers.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Changes in the blood picture after radioiodine therapy of thyroid cancer].

AIM: In this study the effect of radioiodine which was administered because of thyroid carcinoma on blood count and various other parameters was examined. PATIENTS AND METHODS: In 567 patients who had been treated because of a thyroid carcinoma between 1980 and 1990 with radioiodine, changes of hemoglobin, RBC, WBC, platelets, potassium, uric acid, gamma GT, GOT, GPT and AP were measured in correlation with the totally administered dose. RESULT: In low doses (< 18.5 GBq [500 mCi]), which are sufficient in most cases with clinical course without complications, relevant changes of blood count (hemoglobin: < or = 9.0/10.5 g/dl, RBC: < or = 3.1/3.5 10(12)/l (female/male), WBC: < or = 2.5 10(9)/l, platelets: < or = 0.5 10(11)/l) were observed in only 5 out of 469 cases. After moderate doses (> or = 18.5 GBq [500 mCi] and < 37 GBq [1000 mCi]) we found in only 1 out of 77 cases relevant changes. After very high doses (> or = 37 GBq [1000 mCi]), which are used to treat metastases and/or recurrences, thrombopoesis is most sensitive to the radiation exposure of the bone marrow. Relevant decrease of RBC and WBC were observed in 2 out of 21 patients. Pancytopenia (hemoglobin: < or = 12.0/13.5 g/dl, RBC: < or = 3.9/4.3 10(12)/l [female/male], WBC: < or = 3.5 10(9)/l, platelets: < or = 1.4 10(11)/l) occurred in 4 cases. CONCLUSION: In high-dose therapy with radioiodine frequent (monthly, but in any cases before each therapy) controls of blood count are necessary. In patients without metastases or recurrence no relevant changes can be expected in most cases.

Adolescent↗
PubMed1994

TP53 alterations and clinical outcome in low grade astrocytomas.

Thirty-eight WHO grade II astrocytomas and 10 malignant recurrent gliomas in these patients were examined for the presence of TP53 alterations. Seventeen/38 low grade astrocytomas and 6/10 malignant recurrent tumors harbored mutations of the gene detected by SSCP analysis and direct sequencing of PCR products. TP53 mutations in five out of six high grade mutant tumors were already present in the corresponding low grade astrocytomas. In two cases, TP53 mutations present in the low grade astrocytoma could not be demonstrated in the recurrent glioma. Immunohistochemistry with two different antibodies to the human TP53 protein revealed nuclear immunoreaction of tumor cells in 11/38 low grade and in 8/10 recurrent tumors. There was no correlation between the presence of TP53 alteration and clinical course. We conclude that, although TP53 mutations are detectable in a substantial fraction of WHO grade II astrocytomas, they do not appear to play a role in the malignant progression of these tumors and they are not of prognostic significance.

Amino Acid Sequence↗
PubMed1994

Human dopamine D4 receptor gene: frequent occurrence of a null allele and observation of homozygosity.

We report a null mutation in the first exon of the human dopamine D4 receptor (DRD4) gene. The mutation is predicted to result in a truncated non-functional protein and is the first natural nonsense mutation found in a human dopamine receptor gene. It occurs with a frequency of about 2% in the general population. The distribution of the mutation was found to be similar in healthy controls and patients suffering from psychiatric diseases which included schizophrenia, bipolar affective disorder and Tourette's syndrome, indicating that heterozygosity for this mutation in the DRD4 gene is not causally related to major psychiatric diseases. We also identified an adult male who is homozygous for this mutation. He shows no symptoms of major psychiatric illness, but he displays somatic ailments including acousticous neurinoma, obesity and some disturbances of the autonomic nervous system. Some of these symptoms might be related to the absence of functional DRD4 protein.

Alleles↗
PubMed1994

Association and haplotype analysis at the tyrosine hydroxylase locus in a combined German-British sample of manic depressive patients and controls.

Tyrosine hydroxylase (TH) is the key enzyme in the synthesis of catecholamines and may therefore be of aetiological relevance in the development of psychiatric illness. Hipolar affective disorder association studies, with restriction fragment length polymorphisms located in flanking regions of the TH gene, have shown conflicting results. Alleles of a tetranucleotide repeat polymorphism (TH4) located in intron 1 of the gene were tested for association with bipolar affective disorder in a combined German and British sample of 183 bipolar patients and 209 healthy control probands. No differences in TH4 allele frequencies were found in the two groups. A subset of patients and controls was typed with the flanking markers Ty7/BglII and pJ4.7/TaqI and frequencies of two-locus haplotypes were estimated. Linkage disequilibrium was found between TH4-Ty7 and TH4-pJ4.7. Haplotype frequencies did not differ between patients and controls.

Alleles↗
PubMed1994

An estimate on the frequency of duplicated haplotypes and silent alleles of human C4 protein polymorphism. II. Investigations in healthy Negro families.

The first investigation of complete MHC marker data in South African Negroes by segregation analysis in 11 families with up to three generations is presented, including quantitative evaluation of C4 allotype patterns and C4 beta chain determinations according to Steuer et al. (1). The frequency of homo- and heteroduplicated, hybrid, and non-expressed C4 alleles was determined from C4 protein phenotyping, including C4 alpha and beta chains, quantitative estimates of the relative electrophoretic C4 banding patterns by scanning densitometry, and from the other classical MHC markers by submitting all results to the family analysis program (FAP). From unrelated non-diseased individuals (n = 105) in these families with 62 haplotypes, the following frequencies were observed for non-expressed alleles: C4A*Q0 0.1189, C4B*Q0 0.2552, and for the total of heteroduplicated alleles: C4A 0.0645, C4B 0.0608. Applying additionally quantitative determinations of C4 banding patterns, homoduplications such as C4A*3 A*3, C4B*1 B*1, C4B*3 B*3, and the heteroduplication C4A*3 A*2 were assumed. In the investigated individuals the heteroduplications of C4A*12 and C4A*3 with the A*91 allele and of C4B*2 with C4B*92 were observed. It was concluded that not only allele frequencies but also the frequency of heteroduplications seems to be of specific ethnic character. Furthermore, the prior hypothesis that deletion or non-expression at one C4 locus is accompanied by duplication at the other was only confirmed for non-expressed B-alleles with C4A*3 A*91 or C4A*12 A*91.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1993

DNA-minisatellite mutations: recent investigations concerning distribution and impact on parentage testing.

At least 815 meioses were studied in the HinfI polymorphisms of DNA minisatellite loci D1S7, D2S44, D7S21, D7S22, and D12S11 in order to collect data on respective mutation rates. At locus D7S21 (probe MS31) a striking difference between the paternal and maternal mutation rate was observed (1.5% versus 0.2%). This study also describes, how to deal biostatistically with paternal mutations in parentage testing. Possible implications of mutations are illustrated by the description of 2 cases. Case 1 reports an "exclusion" of mother and father with probe MS1. Case 2 describes 2 paternal "exclusions" with probes MS31 and G3. The statistical likelihood for a paternal "exclusion" with 2 of the 5 probes is 0.13%. By omitting probe MS1, this frequency can be reduced to 0.02%. Nevertheless, the second case clearly shows, that informative blood group markers cannot be replaced by DNA polymorphisms.

Alleles↗
PubMed1993

A serine to glycine substitution at position 9 in the extracellular N-terminal part of the dopamine D3 receptor protein: no role in the genetic predisposition to bipolar affective disorder.

Association studies offer a promising tool to investigate the potential role of DNA sequence variation affecting the expression or sequence of proteins in susceptibility to common diseases. We determined the frequency of a DNA polymorphism resulting in a glycine to serine substitution at position 9 in the extracellular N-terminal part of the dopamine D3 receptor protein in a sample of 83 patients suffering from bipolar affective disorder and 100 control subjects. No significant differences between the groups were found. Thus, this substitution, which is the first sequence variation identified in the dopamine D3 receptor gene altering the amino acid sequence of the protein, can be regarded as a protein variant with no major effect on the susceptibility to bipolar affective disorder.

Alleles↗
PubMed1993

The use of microsatellites in zygosity diagnosis of twins.

Although numerous genetic and anthropological markers are available for determining zygosity of twins, there is still a need for a more practical and informative method in zygosity diagnosis. Dinucleotide repeats or other short repeats (microsatellites) are highly variable between individuals and offer a simple, fast, cheap, and exact approach for zygosity determination. The feasibility of a set of microsatellites to be used for this purpose is demonstrated.

Alleles↗
PubMed1992

Biostatistical basis of individualization and segregation analysis using the multilocus DNA probe MZ 1.3: results of a collaborative study.

A collaborative study using the multilocus minisatellite DNA probe MZ 1.3 was carried out to investigate segregation information, mutation rate, DNA fragment frequencies as well as band sharing characteristics. The fingerprint patterns of 393 children as well as 694 unrelated individuals were analysed after digestion of DNA with the restriction enzyme HinfI. A mutation rate of 1% per meiosis or 0.04% per band was found with a mean number of 26 bands/individual. It was shown that maternal and paternal fragments are inherited in equal proportions. Population frequencies of restriction fragments demonstrated a distribution with increasing frequencies in the small fragment size range below 10 kb as well as the absence of very common or very rare fragments. Our data can be used to calculate simple exclusion probabilities based on the number of non-maternal bands in the child.

Biometry↗
PubMed1992

Early signs of cognitive deficits among human immunodeficiency virus-positive hemophiliacs.

A total of 181 human immunodeficiency virus (HIV)-seropositive hemophiliacs and 28 hemophilic controls were evaluated by psychometric tests and by electroencephalogram (EEG). Patients were classified from stages 1-6 according to the immunological criteria of the Walter Reed staging system. Statistical analysis of psychometric data showed an effect of the stage of the disease on test performances, indicating a decline in attention, accumulation of perceptual interferences, decline in visuoperceptual speed and visuomotor response speed and reduced verbal memory performance, especially in stage 6 patients. Comparison of performance levels with normative test data already revealed cognitive deficits in about 20-30% of the patients in stages 2-5. As regards verbal memory, especially learning and recognition of new verbal information were impaired. In contrast, there was no significant deficit for nonverbal memory processing. Compared with the controls, patients exhibited an increasing number of abnormal EEG findings in stages 2-6. As a conclusion, in the stages before acquired immunodeficiency syndrome (AIDS) develops, EEG findings as well as psychometric findings indicate central nervous system involvement of AIDS in about 20-30% of cases, whereas in full-blown AIDS there is a marked increase to 80%. Besides a more general deficit of attention and psychomotor speed as is seen in subcortical dementia, there is evidence for a particular verbal learning disorder, suggesting additional selective impairment of the brain.

AIDS Dementia Complex↗
PubMed1992

Lack of association between dopamine D1 and D2 receptor genes and bipolar affective disorder.

Fifty-six patients with bipolar affective disorder and 69 healthy control subjects were tested for association of restriction fragment length polymorphism alleles at the dopamine D1 and D2 receptor loci. No significant associations were found; thus, the hypothesis that a single mutant form of either receptor gene is responsible for the phenotype of patients with bipolar affective disorder was not supported.

Alleles↗
PubMed1991

Atrioventricular septal defects. Analysis of short- and medium-term results.

Atrioventricular septal defects were repaired in 87 patients from 1981 to 1988. Interventricular communications were present in 73 patients, and major associated anomalies were present in 17 (tetralogy of Fallot in four, double-outlet right ventricle in two, multiple ventricular septal defects in 11). Five deaths occurred in the hospital (5.7%; 70% confidence limits, 3.2% to 9.7%). A preoperative New York Heart Association class V functional condition was the only incremental risk factor (p = 0.02) for death in the hospital. No patient (0%; 70% confidence limits, 0% to 2.15%) had complete heart block. Actuarial survival rate at 80 months was 81.4%. The only incremental risk factor (p = 0.005) leading to reoperation was a preoperative valve incompetence. Actuarial rate at 80 months for freedom from reoperation was 84.2% in the overall group of patients after repair of atrioventricular septal defect. We conclude that an improvement in survival and success rates should be found when a policy of earlier repair is followed.

Actuarial Analysis↗
PubMed1990

Isolation of the DNA minisatellite probe MZ 1.3 and its application to DNA 'fingerprinting' analysis.

A minisatellite probe, MZ 1.3, detecting hypervariable fragment patterns was isolated from a human genomic library. A repetitive sequence of 27 bp length was identified which is contained in the probe approx. 40 times. The MZ 1.3 repeat shows variable homology of 53-73% to the repetitive sequence of the protein III gene of the bacteriophage M13 genome. Polymorphic restriction fragment patterns were found with MZ 1.3 using the enzymes Hinf I, BstN I, Hae III, Mbo I, PstI/Pvu II, and Rsa I. An average of 18 polymorphic fragments was observed using Hinf I as enzyme. The band sharing frequency after Hinf I digestion among unrelated individuals was determined to be 23.8 +/- 7.2%. An example for the application of MZ 1.3 to paternity testing in an incest case is given. The probe can be used with radioactive or non-radioactive detection systems. An approach is presented to compare polymorphic fragment patterns from individuals obtained by independent gel runs on the basis of relative band positions (RBP) and calculated in a computerized analysis.

Base Sequence↗
PubMed1990

[Chemosensitivity studies with soft agar culture systems in ovarian cancer].

Since 1982, chemosensitivity studies have been conducted in our laboratory with 181 tumour samples from 132 woman patients suffering from carcinoma of the ovaries, using the colony test and capillary assays. Colonisation rates were 67% and assay rates between 60 and 47%; in 36 cases the in vitro result was compared with the course of the disease observed in vivo. Whereas in 11 of 12 patients it was possible to correctly assess chemoresistance (in vitro growth inhibition less than or equal to 49%) pretherapeutically, chemosensitivity (growth inhibition greater than or equal to 50%) proved more difficult to confirm, 15 predictions being true and 9 false. To assess the prognostic significance of the test results, survival curves were calculated from the data of 33 patients. With a p-value of 0.49, the courses of disease of "in vitro resistant" and "in vitro sensitive" patients differed only slightly from one another. We can conclude from our experiments, that an important indication for performing the colony test in ovarian carcinoma should always be assumed in patients with a poor prognosis, e.g. in women having a large postoperative residual tumour. If, in such cases, the possibility of chemosensitivity testing via the colony test is considered, this examination may offer the chance of sparing the patient additional strain due to the side effects of a treatment with cytostatics if the latter is most likely to be of no significant use.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Genetic analysis of IDDM: the GAW5 multiplex family dataset.

In a collaborative effort by 12 centers from Europe and North America, data were assembled from 94 multiplex families with insulin-dependent diabetes mellitus (IDDM) for analysis of genetic and other factors of possible etiological importance. The dataset contains information on the following genetic markers: HLA-DR beta and -DQ beta restriction fragment length polymorphisms (RFLPs), three RFLPs detected with two probes that map 5' to the insulin gene, the serologically defined HLA loci, and the immunoglobulin allotypes. Data also were included for auto-antibodies to insulin and pancreatic islet cells as possible indicators of pathogenesis and for antibodies to certain viruses that have been implicated as "triggering" agents in IDDM. Medical history of family members was obtained by means of a uniform questionnaire. Identical copies of the dataset were distributed to anyone wishing to participate in the analysis for the IDDM component of GAW5. The multiplex IDDM family dataset is now available on request for further analysis.

Adolescent↗