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B Christensen

Publications and source records attributed to B Christensen.

At least 91 records · Page 5Linked to original sources
PubMed1996

Prenatal detection of chromosome aneuploidies in uncultured chorionic villus samples by FISH.

We developed a 1-d FISH assay for detection of numerical chromosome abnormalities in uncultured chorionic villus samples (CVS). Probes specific for chromosomes 13, 18, 21, X, and Y were used to determine ploidy by analysis of signal number in hybridized nuclei. Aneuploidy detection using this assay was directly compared with the results obtained by conventional cytogenetic analysis in a consecutive, clinical study of 2,709 CVS and placental samples. The FISH assay yielded discrete differences in the signal profiles between cytogenetically normal and abnormal samples. On the basis of these results, we generated FISH-assay cutoff values that discriminated between karyotypically normal and aneuploid samples. Samples with mosaicism and a single sample with possible heritable small chromosome X probe target were exceptions and showed poor agreement between FISH results and conventional cytogenetics. We conclude that the FISH assay may act as a more accurate and less labor-demanding alternative to "direct" CVS analysis.

Aneuploidy↗
PubMed1996

Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR.

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, a methyl donor in the conversion of homocysteine to methionine. Patients with severe MTHFR deficiency have hyperhomocysteinemia, hypomethioninemia, and a range of neurological and vascular findings with a variable age at onset. We have previously described nine mutations in patients with severe MTHFR deficiency. A mild form of MTHFR deficiency, associated with a thermolabile enzyme, has been proposed as a genetic risk factor for cardiovascular disease and for neural tube defects. We have shown that a common missense mutation (an alanine-to-valine substitution) encodes this thermolabile variant. We now report an additional five mutations causing severe MTHFR deficiency and an analysis of genotype (alanine/valine status) and enzyme thermolability in 22 patients with this inborn error of metabolism. Six of these patients have four mutations in the MTHFR gene-two rare mutations causing severe deficiency and two mutations for the common alanine-to-valine mutation that results in thermolability. Even in severe MTHFR deficiency, the thermolabile variant is frequently observed, and there is a strong relationship between the presence of this variant and increased enzyme thermolability.

Adolescent↗
PubMed1995

Image analysis in comparative genomic hybridization.

Comparative genomic hybridization (CGH) is a new technique by which genomic imbalances can be detected by combining in situ suppression hybridization of whole genomic DNA and image analysis. We have developed software for rapid, quantitative CGH image analysis by a modification and extension of the standard software used for routine karyotyping of G-banded metaphase spreads in the Magiscan chromosome analysis system. The DAPI-counterstained metaphase spread is karyotyped interactively. Corrections for image shifts between the DAPI, FITC, and TRITC images are done manually by moving the three images relative to each other. The fluorescence background is subtracted. A mean filter is applied to smooth the FITC and TRITC images before the fluorescence ratio between the individual FITC- and TRITC-stained chromosomes is computed pixel by pixel inside the area of the chromosomes determined by the DAPI boundaries. Fluorescence intensity ratio profiles are generated, and peaks and valleys indicating possible gains and losses of test DNA are marked if they exceed ratios below 0.75 and above 1.25. By combining the analysis of several metaphase spreads, consistent findings of gains and losses in all or almost all spreads indicate chromosomal imbalance. Chromosomal imbalances are detected either by visual inspection of fluorescence ratio (FR) profiles or by a statistical approach that compares FR measurements of the individual case with measurements of normal chromosomes. The complete analysis of one metaphase can be carried out in approximately 10 minutes.

Humans↗
PubMed1995

Regional cerebral activation during auditory stimulation in patients with cochlear implants.

OBJECTIVE: To evaluate a possible change in the regional cerebral blood flow (rCBF) in the language-related cortical areas of the brain during stimulation of a cochlear implant. METHODS: The rCBF was measured by single-photon emission tomography and inhalation of Xenon Xe 133, providing information on the regional functional level of the brain. A supplementary single-photon emission tomographic scan was also performed, using technetium Tc 99m hexamethylpropyleneamineoxime as a flow marker. The rCBF was measured during rest (baseline) and during auditory stimulation by presenting white noise and running speech to the ear with the implant. PATIENTS: Five deaf patients who had undergone intracochlear or extracochlear implantation surgery. RESULTS: As in subjects with normal hearing, notable activation was not found in the relevant primary auditory cortex on stimulation with white noise. Two of the patients with implants had an increase in the rCBF in the relevant contralateral hemisphere on stimulation with running speech, but in the other three patients, a notable increase was not detected. This lack of increase in the rCBF on speech stimulation was consistent with the lack of speech recognition experienced by the subjects when using the implant. In one subject, the implant had a beneficial effect on speech understanding that was associated with a significant increase in the cerebral blood flow in the Broca's speech area and Wernicke's second speech area. CONCLUSIONS: Although the results are preliminary, the single-photon emission tomographic technique may be useful when evaluating the function of a cochlear implant. The method may also help select patients and/or ears for cochlear implantation. Four of five patients had functional defects of auditory relevant cortical areas, suggesting that their deafness might be associated with central impairment in addition to their cochlear defects.

Acoustic Stimulation↗
PubMed1995

Effects of folate deficiency on embryonic development.

While there is strong evidence that folate deficiency including the use of anti-folate drugs in early pregnancy is teratogenic and may lead to a range of serious abnormalities of the developing fetus including intrauterine death, the mechanism(s) for these effects have not yet been delineated. In neural tube defects, there is increasing evidence that marginal folate status exacerbates the effect of an underlying genetic defect in the mother, the fetus, or both. An abnormal relationship between the ingestion of folate and the folate levels in red blood cells has been found in women who have given birth to infants with neural tube defects. Periconceptional folate supplementation has been shown to give effective protection against the development of neural tube defects. The mechanism of the prevention is as yet unknown. However, folic acid will not prevent all cases of neural tube defect. Moreover, neither determinations of periconceptional vitamin profiles (Mooij et al, 1993) nor determinations of methylmalonic acid and homocysteine levels will detect all women at risk. Anencephaly and spina bifida can be identified prenatally by detection of excessive levels of alpha-fetoprotein in amniotic fluid and maternal serum and by ultrasonographic scanning (Wilson and Rudd, 1993). Both genetic counselling and prenatal diagnosis should be offered to women who are recognized to be at high risk. Research into the underlying biology of neural tube defects is of major importance. The identification of underlying genetic defects would allow for genetic testing and better counselling of families at risk for the occurrence of a neural tube defect.

Animals↗
PubMed1995

[Endometriosis--diagnosis and therapy. Results of a current survey of 6,700 gynecologists].

The aim of this study is to obtain an actual survey of diagnostic and therapeutic procedures of endometriosis (EMT) in gynaecological practice in West Germany. A questionnaire was sent to 6,700 gynaecologist; 1,364 responded. Approximately 5% of all the patients in daily practice have symptoms related to EMT. Most of the patients are in their twenties. The common clinical symptoms of EMT are dysmenorrhoea (91.8%), infertility (79.7%), pelvic pain (70.9%), menstrual irregularity (46.3%), dyspareunia (21.8%) and painful defaecation (12.8%). The diagnostic standard is laparoscopy, but there are many doctors diagnosing EMT also by means of gynaecological examination (23.8%) or ultrasound (21.3%) - especially in young patients. Hormones are the first choice of therapy. Progestins and danazol are preferred. GnRH-analogues are only used by a smaller proportion of gynaecologists - particularly in infertile patients. Surgical procedures with or without hormonal suppression are another line of therapy adapted by 70.9% of the gynaecologists, which are often preferred in infertile patients. Psychological problems in EMT are caused by the uncertainties between EMT and infertility and by the difficulties between physiological menstrual discomfort and pain caused by EMT. 68.5% of the gynaecologists suggest that more information beyond diagnosis and therapy should be given to the patients. Promotion of self-supporting groups should be encouraged by the doctors.

Adult↗
PubMed1995

Characteristics of attenders and non-attenders at health examinations for ischaemic heart disease in general practice.

OBJECTIVE: To clarify the importance of health beliefs and some socio-demographic data for accepting an invitation to take part in a health examination by comparing attenders and non-attenders with respect to health beliefs and social status. DESIGN: Multipractice study including questionnaires for men. SETTINGS: 65 GPs in two areas in the county of Aarhus, Denmark, invited 2452 40-49 year old men to a health examination for ischaemic heart disease. The examination was free in one area, whereas there was a fee in the other. All 1272 attenders and 423/1180 non-attenders completed the questionnaire. RESULTS: The attendance rate was 66% in the area with free examination and 37% in the fee-paying area. The attendance was significantly higher for cohabitants than for single men in both areas. There was a slightly higher attendance of men with an occupational training in both areas, but the difference was not significant. In general, all agreed that IHD is a serious disease, and that it can be prevented by a personal effort. There were only minor differences in the attenders' and non-attenders' health beliefs. CONCLUSION: The main conclusion is that 40-49 year old men are in general concerned about IHD. Whether they want to have a health examination for IHD depends mainly on its availability (exemplified here as fee versus free), since the differences were small with respect to health beliefs between attenders and non-attenders.

Adult↗
PubMed1995

Psychological reactions to information about risk of ischaemic heart disease in general practice.

OBJECTIVE: To examine the psychological reactions in 40-49 year old men diagnosed as having an increased risk for the development of ischaemic heart disease at a health examination in general practice. DESIGN: A multipractice study including a questionnaire about the psychological well-being before and 6 months after a health examination aimed at finding an increased risk for ischaemic heart disease. SETTING: General practice in the county of Aarhus, Denmark. Sixty five general practitioners. PARTICIPANTS: 123 men with and 150 men without an increased risk of ischaemic heart disease. OUTCOME MEASURES: Psychological well-being was measured by the General Health Questionnaire (12 item version). RESULTS: No significant change in GHQ-scores after the screening examination. CONCLUSION: Information about increased risk of IHD in 40-49 year old men at a health examination in general practice did not change the psychological well-being as measured by a General Health Questionnaire 6 months after the examination.

Adult↗
PubMed1995

The effect of prosthetic rehabilitation in lower limb amputees.

The objectives of this project were to ascertain whether, to date, the views concerning the determination of prosthetic candidacy have been optimal and whether the training methods applied have been effective and have resulted in constant use of the prosthesis after conclusion of the training programme. Secondly it was intended to set up guidelines for future budgeting as well as providing a reference framework for the process of rehabilitation. An inquiry based on questionnaires was the first phase in a quality assurance project carried out among 29 amputees trained in 1990 and 1991. The result of the inquiry was that rehabilitation using PTB prostheses for 19 trans-tibial amputations in 18 cases (one patient was a bilateral trans-tibial amputee) led to constant use of the prosthesis and that advanced age was no hindrance to constant use in this group. For 10 trans-femoral amputees the inquiry revealed that advanced age combined with problems of donning the prosthesis was a hindrance to constant use in two cases. It is concluded that there is a need for testing/developing new types of femoral prostheses. The patients' evaluation of the rehabilitation process and their prostheses stresses the need for communication between the team of professionals and the patients in the decision process concerning the provision of a prosthesis as well as the provision of complete information on the patients' future functional possibilities. Qualitative measurements must include the kind and number of medical complications and the social conditions of the amputee as well as tests of physical and mental resources.

Adult↗
PubMed1995

Comparative genomic hybridization in clinical cytogenetics.

We report the results of applying comparative genomic hybridization (CGH) in a cytogenetic service laboratory for (1) determination of the origin of extra and missing chromosomal material in intricate cases of unbalanced aberrations and (2) detection of common prenatal numerical chromosome aberrations. A total of 11 fetal samples were analyzed. Seven cases of complex unbalanced aberrations that could not be identified reliably by conventional cytogenetics were successfully resolved by CGH analysis. CGH results were validated by using FISH with chromosome-specific probes. Four cases representing common prenatal numerical aberrations (trisomy 21, 18, and 13 and monosomy X) were also successfully diagnosed by CGH. We conclude that CGH is a powerful adjunct to traditional cytogenetic techniques that makes it possible to solve clinical cases of intricate unbalanced aberrations in a single hybridization. CGH may also be a useful adjunct to screen for euchromatic involvement in marker chromosomes. Further technical development may render CGH applicable for routine aberration screening.

Chromosome Aberrations↗
PubMed1995

Payment and attendance at general practice preventive health examinations.

BACKGROUND AND OBJECTIVES: This study's purpose was to determine how conditions of payment influence attendance at preventive health examinations. METHODS: A multi-practice study of 65 general practitioners (GPs) was conducted in two areas in the county of Aarhus, Denmark. The GPs invited 2,452 men aged 40-49 to a preventive health examination for coronary heart disease (CHD). The examination was free in one area but cost $40 in the other area. A risk profile was estimated, based on a summation of points for risk factors for CHD, including blood pressure, serum cholesterol, smoking behavior, body mass index, and family history of CHD. RESULTS: Attendance at the examinations was 37% in the required payment area and 66% in the free area. Of the total attenders, 13% had an increased risk of CHD. A slight but significant tendency, a lower risk for developing CHD, existed among attenders who paid for the examination. CONCLUSION: A requirement for payment for health examination leads to fewer patients obtaining examinations.

Adult↗
PubMed1994

Development and reversion of methionine dependence in a human glioma cell line: relation to homocysteine remethylation and cobalamin status.

We investigated the biochemical changes which accompanied the development and reversion of methionine dependence in a human glioma cell line GaMg. This cell line attained a higher proliferation rate and more malignant morphology with increasing passages in vitro. Early passages (P10, P25, and P45) were able to grow in a methionine-deficient medium supplemented with homocysteine (Met-Hcy+), while a later passage (P60) had lost this ability, i.e., it had become methionine-dependent. From P60 cells, a methionine-independent revertant (P60R) was established by exposing the cells to 5-aza-2-deoxycytidine, followed by culture in a Met-Hcy+ medium. In these genetically related cell lines, we investigated homocysteine remethylation and the functional state of cobalamin-dependent methionine synthase, the enzyme responsible for remethylation of homocysteine to methionine. The methionine synthase activity in cell extracts was similar in all cell sublines. Intact cell methionine biosynthesis and nitrous oxide-dependent homocysteine export reflect homocysteine remethylation in cells cultured in a Met-Hcy+ and methionine-containing (Met+Hcy-) medium, respectively. Both of these parameters, as well as the cellular content of the substrate 5-methyltetrahydrofolate, and the cofactor methylcobalamin, in addition to adenosylcobalamin, were high in P10, declined progressively in P45 and P60, and were restored in P60R. P25 cells had some unique features among the methionine-independent phenotypes because both homocysteine remethylation and the level of 5-methyltetrahydrofolate were low in Met+Hcy- medium. The maximal homocysteine export rate in the presence of nitrous oxide, which reflects the overall transmethylation rate, was high in P60 and even higher in P60R compared to the lower passages. The basis for development of methionine dependence during culture of this glioma cell line seems related to the combined effects of reduced methionine biosynthesis and an increased overall transmethylation rate. The single parameter which most closely correlated to the ability to use homocysteine for growth was methylcobalamin. These data support a model for methionine dependence, which implies impaired provision of cobalamin to methionine synthase.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1994

Fluorescence in situ hybridization with a chromosome 21-specific cosmid contig: 1-day detection of trisomy 21 in uncultured mesenchymal chorionic villus cells.

We present a modified, fast trisomy 21 detection assay using fluorescence in situ hybridization (FISH) on uncultured mesenchymal chorionic villus cells. The whole test takes about 24 h. We used a cosmid contig as a probe and modified an in situ sample preparation method first described by Klinger et al. (1992). The assays saves time and cost of culture in comparison with a previously described trisomy 21 detection FISH assay (Bryndorf et al., 1993). A small blind clinical study comparing the modified and the previously described FISH assays using mesenchymal chorionic villus cells showed comparable results and concordance with conventional cytogenetic analysis. The frequency of nuclei with three hybridization signals from samples disomic for chromosome 21 ranged from 0 to 8 per cent with both assays, while trisomic samples had 60-80 and 54-90 per cent of the mesenchymal nuclei with three signals in the modified and previously described assays, respectively. Normal (disomic) and trisomic mesenchymal chorionic villus samples can be distinguished clearly and rapidly without culture in the modified assay.

Base Sequence↗
PubMed1994

Prenatal aneuploidy detection in interphase cells by fluorescence in situ hybridization (FISH).

FISH is a quick, inexpensive, accurate, sensitive and relatively specific method for aneuploidy detection in samples of uncultured chorionic villus cells and amniotic fluid cells. FISH allows detection of the autosomal trisomies 13, 18 and 21 and X and Y abnormalities and any other chromosome abnormality for which a specific probe is available. The detection rate of these abnormalities is high in informative samples which have a concordance of > 99.5% with cytogenetic results. A relatively high number of abnormal cases are found in uninformative samples. However, such samples should be regarded as samples to be investigated further. Clinical experience with the use of FISH for prenatal diagnosis is now beyond 10,000 cases; a number of clinical protocols and smaller trials have also been carried out, resulting in 90% of attempted analyses giving informative results with a high detection rate and extraordinarily low false-positive and false-negative rates. Unsolved problems remain, such as occasional technical failures, admixtures of maternal blood and up to 20% uninformative scoring results, especially for abnormal specimens. FISH is at present used as an adjunct to classical cytogenetic analysis. However, this should not be interpreted as meaning that FISH could not be used as a methodology in its own right. If FISH were to be considered a diagnostic test then this might be the case, due to the risk of false-negative and false-positive results and the fact that FISH does not allow a diagnosis of certain structural abnormalities. If, on the other hand, FISH is considered a screening test, which means that in all abnormal (or indeterminate) cases, classical cytogenetic analysis would follow the abnormal screening test, the accuracy which is potentially higher than for other screening methods, for example in cases of trisomy 21, justifies FISH as a prenatal screening test in its own right.

Amniotic Fluid↗