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At least 55 records · Page 3Linked to original sources

Slow rehabilitation of a traumatic lower limb amputee.

A 65-year-old male (GM) was referred to the physiotherapy department of the regional limb fitting centre for outpatient rehabilitation following a right transfemoral amputation five weeks previously. He had been knocked down by a bus and suffered a crush injury to the right leg resulting in a stable fracture to the right pubic ramus, a fractured skull and orbital bone. Immediately following admission to the local district general hospital, his right leg was amputated at the transfemoral level. He was nursed post-operatively in ITU for three days and was ventilated during this time. GM was then transferred to the general orthopaedic ward. He received physiotherapy throughout his hospital stay by ward-based physiotherapists--not experts in amputee management but with access to specialist advice. Early physiotherapy was primarily concerned with respiratory care and maintenance of limb mobility and function in bed. Gentle, active stump exercises were commenced on the first post-operative day. GM sat out of bed on the sixth day and stood with the support of two people on the eighth day. His wound was healing well and treatment in the physiotherapy gym began the same day. Use of the pneumatic post-amputation mobility aid (PPAM aid) (Redhead, 1983; Marks, 1996) was started on day nine. However, progress with this early walking aid (EWA) was slow and GM achieved independent walking using parallel bars on the eighteenth post-operative day.

Aged↗

[First responder defibrillation in the LAGO-die Therme--results and experiences].

The use of automated external defibrillator (AED) by persons other than paramedics and emergency medical technicians is advocated by several US- and European organizations. However, at the present time it is still unclear to identify public places with a high incidence of out-of-hospital cardiac arrest. There are few data on the potential impact of public access defibrillators on survival after out-of-hospital cardiac arrest in sporting arenas or water parks. Therefore, we studied prospectively incidence of out-of-hospital cardiac arrest in the LAGO-die Therme in Herne. This is one of the most important swimming parks in Europe and member of the European Waterpark Association EWA. Eight AEDs were placed in the waterpark LAGO-die Therme. The locations where the defibrillators were stored were chosen to make possible a target interval of 60 seconds from collapse to first defibrillation. Twenty waterpark officers were instructed in cardiopulmonary resuscitation and in the use of the AED. During November 16, 2001 and December 31, 2004, 2.05 Mio. visitors were counted in the LAGO. Out-of-hospital cardiac arrest occurred in none of them. AED were used in two visitors with non arrhythmogenic syncope, no shock was delivered. Questionaires were done in 588 visitors (336 males, 252 females, mean age 38+21 years) in 2002 and in 579 visitors (322 males, 257 females, mean age 37+/-25 years) in 2004. In 2002, 77% of the visitors noticed the AED and, therefore, 49% performed more sporting activities. In addition, in 2004, AED was noticed by 480 visitors (83%) and 277 visitors (48%) did more sporting activities. There were no significant differences between 2002 and 2004 (p=ns). Despite no out-of-hospital cardiac arrest in the waterpark during the 3 year follow- up, it seems reasonable to install AED in sporting places with thousands of visitors per year.

Adult↗

Esketamine multi-omic biomarker evaluation in major depressive disorder (EMBER-MDD): concept, objectives and methodologies of a non-clinical investigator-initiated study.

Treatment resistance (TR) in major depressive disorder (MDD) affects a substantial minority of patients and is hard to recognize early, delaying intensified care. The Esketamine multi-omic biomarker evaluation in MDD (EMBER-MDD) is a non-interventional, investigator-initiated, in-vitro study within the EU Psych-STRATA programme, analyzing biospecimens collected in the randomized INTENSIFY study and the mirror OBS-TR cohort after participants complete treatment. EMBER-MDD aims to discover individual-omic and integrated multi-omic (hypothesis-free) biomarkers and signatures associated with TR risk, and molecular correlates of clinical response to esketamine nasal spray versus treatment as usual (TAU). Biomaterials will derive from approximately 420 adults with MDD (estimated n = 210 esketamine; n = 210 TAU) and include whole blood, RNA-stabilized whole blood, plasma and serum, sampled at baseline and, when feasible, during and after treatment (up to ~ 5,040 aliquots stored at - 80 °C). Genomics will use baseline DNA genotyping on Illumina Infinium GSA v3.0+MD arrays; epigenomics will profile genome-wide DNA methylation across time points using MethylationEPIC v2.0; transcriptomics will employ mRNA-seq (NovaSeq X/ X Plus); and proteomics/ metabolomics will be generated using high-throughput Olink and/ or Biocrates platforms. Each layer will undergo state-of-the-art preprocessing and analyses (e.g., GWAS/ PRS, EWAS, differential expression, WGCNA, pathway and network analyses), followed by integrative strategies including QTL mapping (meQTL/ eQTL/ pQTL/ mQTL) and intermediate-fusion machine learning with nested cross-validation, explainable AI (SHAP/ LIME) and treatment-effect modelling. All outputs are research-only and will not support individual efficacy, tolerability, or clinical decision-making. The study will deliver robust biosignatures and mechanistic hypotheses to guide future validation and inform stratified, molecularly guided intervention strategies in subsequent prospective trials. Trial registration number: 2023-506617-21-00 and 2025-178-f-S.

Humans↗

The effects of oral and transdermal hormone replacement therapy on C-reactive protein levels and other inflammatory markers in women with high risk of thrombosis.

INTRODUCTION: In the estrogen in venous thromboembolism (EVTET) study of 140 women with a history of venous thromboembolism (VTE), oral hormone replacement therapy (HRT) was associated with strong activation of coagulation markers and increased risk of recurrent VTE. No such associations were observed in the estrogen women atherosclerosis (EWA) study of 118 women with established coronary artery disease who were given transdermal HRT. OBJECTIVES AND METHODS: The aim of the present study was to evaluate the effects of oral and transdermal HRT on levels of C-reactive protein (CRP), which was assayed with a highly sensitive method. We also evaluated the effects on other inflammatory markers and the influence of possible confounding factors. RESULTS: Oral HRT was associated with a significant increase in CRP after 3 months as compared with placebo (median 79% [95% confidence interval 36-119%] versus -4% [-13 to 10%], p = 0.001). These changes sustained after 12 months. Among those allocated HRT, the median increase in CRP was higher in women who subsequently developed recurrent thrombosis (median 328%, n = 5, versus 54%, n = 60). TNF-alpha levels decreased significantly by mean -10% [-15 to -5%] versus 3% [-4 to 10%], p=0.004. Soluble VCAM-1 decreased in the HRT group compared to the placebo group (mean -13% [-18 to -8%] versus 1%, [-3 to 5%], p < 0.001). There were no significant changes in levels of IL-6, TGF-beta or P-selectin. On transdermal HRT no significant changes in CRP were observed after 3 and 12 months of treatment. CONCLUSIONS: Our findings substantiate that oral HRT containing estradiol is associated with a marked and rapid increase in CRP, whereas transdermal treatment is not. However, this increase on oral treatment was associated with no increases of other inflammatory markers.

Administration, Cutaneous↗

Scalable screening of ternary-code DNA methylation dynamics associated with human traits.

Epigenome-wide association studies (EWASs) are transforming our understanding of the interplay between epigenetics and complex human traits. We introduce the methylation screening array (MSA) to enable scalable and quantitative screening of trait-associated DNA cytosine modifications in large human populations. The MSA integrates EWASs and cell-type-linked methylation signatures, covering diverse traits and diseases. Using the MSA to profile the ternary-code DNA methylations-dissecting 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and unmodified cytosine-revealed a previously unappreciated role of 5hmC in mediating human trait associations and epigenetic clocks. We demonstrated that 5hmCs complement 5mCs in defining epigenetic cell identities. In-depth analyses highlighted the cell-type context of EWAS and genome-wide association study (GWAS) hits. Targeting aging, we uncovered shared and tissue-specific 5hmC aging dynamics and tissue-specific rates of mitotic hyper- and hypomethylation. These findings chart a landscape of the complex interplay of the two forms of cytosine modifications in diverse human tissues and their roles in health and disease.

Humans↗

Effective energy resolution and scatter rejection in nuclear medicine.

All available imaging devices in nuclear medicine have finite energy resolution. This leads to inclusion of scattered radiation, which in turn degrades the image quality. Different scatter correction schemes therefore try to eliminate the effect of scattered radiation. On the other hand, improvement of the camera's intrinsic energy resolution would reduce the amount of detected scattered radiation as well. A simple model was developed in order to simulate the influence of the energy resolution on the camera response. It is shown that improvement of the energy resolution and scatter correction schemes have a similar effect on the point spread function. On this basis, it is suggested that 'effective energy resolution' be used as a new measure for the effectiveness of scatter correction schemes. As an example, this is done for energy-weighted acquisition (EWA), a scheme wherein each event contributes imaging information according to a real-valued, energy-indexed weighting function.

Models, Theoretical↗

Adaptive filter for event-related bioelectric signals using an impulse correlated reference input: comparison with signal averaging techniques.

Many bioelectric signals result from the electrical response of physiological systems to an impulse that can be internal (ECG signals) or external (evoked potentials). In this paper an adaptive impulse correlated filter (AICF) for event-related signals that are time-locked to a stimulus is presented. This filter estimates the deterministic component of the signal and removes the noise uncorrelated with the stimulus, even if this noise is colored, as in the case of evoked potentials. The filter needs two inputs: the signal (primary input) and an impulse correlated with the deterministic component (reference input). We use the LMS algorithm to adjust the weights in the adaptive process. First, we show that the AICF is equivalent to exponentially weighted averaging (EWA) when using the LMS algorithm. A quantitative analysis of the signal-to-noise ratio improvement, convergence, and misadjustment error is presented. A comparison of the AICF with ensemble averaging (EA) and moving window averaging (MWA) techniques is also presented. The adaptive filter is applied to real high-resolution ECG signals and time-varying somatosensory evoked potentials.

Algorithms↗

The tissue-specific effects of glucose-lowering drug targets on aging mediated through DNA methylation: a multi-omics genetic study.

BACKGROUND: DNA methylation plays a key role in mediating the anti-aging effects of glucose-lowering drugs. This study aims to systematically explore the potential anti-aging effects of target genes of FDA-approved glucose-lowering drugs and the underlying epigenetic mediators. METHODS: We conducted a two-sample Mendelian randomization (MR) study to investigate the putative causal relationships between the gene expression levels of glucose-lowering drug targets and 10 aging-related phenotypes, followed by a two-step MR to estimate the mediation effect of DNA methylation. Drug candidates were selected according to the latest review of clinical drug use for type 2 diabetes, and their target genes were obtained from the DGIdb. Tissue-specific cis-expression quantitative trait loci (eQTLs) from GTEx Consortium were selected as genetic instruments to proxy the expression level of drug-target genes. Glycemic phenotypes were used as positive controls to validate the instruments. The cis- and trans-methylation QTLs of Cytosine-phosphate-Guanine sites near the drug target genes were obtained from GoDMC Consortium. Additionally, we performed enrichment analyses focused on tissue specificity and aging pathways to further corroborate our findings. RESULTS: We obtained 194 target genes interacting with 36 FDA-approved anti-diabetic drugs, of which the tissue-specific eQTLs were used to proxy the drug target effects. MR showed strong evidence that nine interacting genes of six glucose-lowering drugs showed anti-aging potential on one or more aging-related phenotypes mediated by DNA methylation: EHMT2, HSPA4, IGF2BP2, IRS1, LPL, NDUFAF1, NDUFS3, SLC22A3, and TCF7L2. These genes were distributed in 17 tissues, especially in the central nervous system, suggesting a potential neural component in their anti-aging effects. For instance, expression of EHMT2 in several brain basal ganglia regions, where the gene interacted with Tolazamide, showed a protective effect on frailty (odds ratio (OR) in caudate&#x2009;=&#x2009;1.02, 95%CI&#x2009;=&#x2009;1.01-1.04, FDR adjusted P&#x2009;=&#x2009;1.69&#x2009;&#xd7;&#x2009;10-2; OR in putamen&#x2009;=&#x2009;1.02, 95% CI&#x2009;=&#x2009;1.01-1.03, PFDR&#x2009;=&#x2009;3.37&#x2009;&#xd7;&#x2009;10-2, OR in nucleus accumbens&#x2009;=&#x2009;1.02, 95% CI&#x2009;=&#x2009;1.01-1.04, PFDR&#x2009;=&#x2009;3.37&#x2009;&#xd7;&#x2009;10-2). These associations were externally validated by searching literature evidence in existing EWAS and TWAS studies, as well as evidence from enrichment analyses. CONCLUSIONS: This study prioritizes nine glucose-lowering genes as anti-aging drug targets in specific tissues and prioritizes their epigenetic regulation through DNA methylation for future drug development.

DNA Methylation↗

Advancing translational exposomics: bridging genome, exposome and personalized medicine.

Understanding the interplay between genetic predisposition and environmental and lifestyle exposures is essential for advancing precision medicine and public health. The exposome, defined as the sum of all environmental exposures an individual encounters throughout their lifetime, complements genomic data by elucidating how external and internal exposure factors influence health outcomes. This treatise highlights the emerging discipline of translational exposomics that integrates exposomics and genomics, offering a comprehensive approach to decipher the complex relationships between environmental and lifestyle exposures, genetic variability, and disease phenotypes. We highlight cutting-edge methodologies, including multi-omics technologies, exposome-wide association studies (EWAS), physiology-based biokinetic modeling, and advanced bioinformatics approaches. These tools enable precise characterization of both the external and the internal exposome, facilitating the identification of biomarkers, exposure-response relationships, and disease prediction and mechanisms. We also consider the importance of addressing socio-economic, demographic, and gender disparities in environmental health research. We emphasize how exposome data can contextualize genomic variation and enhance causal inference, especially in studies of vulnerable populations and complex diseases. By showcasing concrete examples and proposing integrative platforms for translational exposomics, this work underscores the critical need to bridge genomics and exposomics to enable precision prevention, risk stratification, and public health decision-making. This integrative approach offers a new paradigm for understanding health and disease beyond genetics alone.

Humans↗

Characterization of DNA methylation in PBMCs and donor-matched iPSCs shows age-related methylation is reset during stem cell reprogramming.

DNA methylation is an important epigenetic mechanism that helps define and maintain cellular functions. It is influenced by many factors, including environmental exposures, genotype, cell type, sex, and aging. Since age is the primary risk factor for developing neurodegenerative diseases, it is important to determine if age-related DNA methylation is retained when cells are reprogrammed to an induced Pluripotent Stem Cell (iPSC) state. Here, we selected peripheral blood mononuclear cells (PBMCs; n&#x2009;=&#x2009;99) from a cohort of diverse and healthy individuals enrolled in the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT) study to reprogram to iPSCs. After reprogramming, the resulting iPSCs were evaluated for DNA methylation signatures to determine if they reflect the confounding factors of aging and environmental effects. Data from genome-wide DNA methylation arrays in both cell types showed that age-related methylation measured by epigenetic clocks is largely reset to an early methylation age after reprogramming of PBMCs to iPSCs. We further examined the epigenetic age of each cell type using an Epigenome-wide Association Study (EWAS) and identified a set of methylation Quantitative Trait Loci in each cell type. Our results show that age-related DNA methylation is largely reset in iPSCs, and each cell type has a unique set of methylation sites that are modified by population-level genetic variation.

DNA Methylation↗

A 2-year follow-up of 120 Swedish female alcoholics treated early in their drinking career: prediction of drinking outcome.

BACKGROUND: One hundred twenty women alcoholics recruited to a treatment program called EWA (Early Treatment for Women With Alcohol Addiction) were studied. The selected women were not previously treated for alcohol abuse. METHODS: The women were followed up by use of a structured personal interview, biomarkers sensitive for alcohol abuse (i.e., glutamyl transpeptidase), and questionnaires, by using defined criteria for abstinence, social drinking, satisfactory drinking outcome, and unsatisfactory drinking outcome. RESULTS: Drinking outcome was good (i.e., total abstinence, social drinking, or satisfactory drinking outcome) for 67% of the women during the total follow-up time, by use of strict criteria for relapse. The results were corroborated by the biomarkers. Similar results were reported from two previously studied groups of women from the same department. However, the frequency of abstinence was higher and social drinking was significantly lower among this sample of women. Daily drinking, the use of sedatives, and a long duration of pretreatment alcohol abuse predicted an unfavorable outcome. However, a long duration of outpatient treatment predicted a good outcome, whereas treatment dropout was related to an unsatisfactory drinking outcome. A majority of the women (96%) rated the treatment experience and the treatment program favorably. The overall good results might reflect the selection of the subjects studied. CONCLUSIONS: Improving treatment program adherence would probably improve outcome for the women with an unsatisfactory drinking outcome.

Adult↗

[Operatory strategies and information management of nursing work in the hospital context].

The paper examines the relationship between operatory strategies and information process used by nurses, in hospital context, in order to regulate their ongoing activities. As a conceptual framework, a cognitive ergonomics model was adopted, linking concepts of work regulation and representation to action. The Ergonomics Work Analyses tool (EWA) was used to collect data. The results show that the cognitive strategies used by nurses, in the decision-making process, are based on their ongoing activities as in the preparation of personal notes, aiming, in particular, at reducing their mental workload and assuring the viability of their actions.

Ergonomics↗

Increased interleukin-18 content and angiogenic activity of sera from diabetic (Type 2) patients with background retinopathy.

Hyperglycaemia increases inflammatory cytokine concentration in the blood. Elevated levels of interleukin-18 (IL-18), a cytokine belonging to the interleukin-1 (IL-1) family, were recently reported in patients with Type 2 diabetes mellitus (DM2) and nephropathy. The aim of the present work was an examination of IL-18 concentration in the sera of elderly DM2 patients with nonproliferative retinopathy and age-matched control people and an estimation whether this cytokine plays pro- or anti-angiogenic role in in vivo angiogenic activity of their sera in mice cutaneous angiogenesis test. Recombinant human IL-18 injected intradermally to murine skin induced significant neovascular reaction. DM2 patients sera contained higher concentration of IL-18 and induced stronger neovascular reaction in mice skin than did the sera of corresponding control people. Sera from both groups of people after neutralization with antihuman IL-18 antibodies lost substantial part of their angiogenic activity.

Aged↗

New arylpiperazine 5-HT(1A) receptor ligands containing the pyrimido[2,1-f]purine fragment: synthesis, in vitro, and in vivo pharmacological evaluation.

New 1H,3H-pyrimido[2,1-f]purine-2,4-dione derivatives of arylpiperazine (11-22) were prepared and evaluated in vitro for their affinity for 5-HT(1A), 5-HT(2A), alpha(1), and D(2) receptors. The tested compounds showed high affinity for 5-HT(1A) and alpha(1) receptors (K(i) = 1.1-87 and 10-62 nM, respectively) and moderate to low affinity for 5-HT(2A) (K(i) = 56-881 nM) and D(2) receptors (K(i) = 94-1245 nM). Compounds 14, 15, 18, 19, and 21, mostly 3'-chlorophenylpiperazine derivatives, can be classified as mixed 5-HT(1A)/5-HT(2A)/alpha(1) ligands. Compound 13, which showed the highest 5-HT(1A) receptor affinity (K(i) = 1.1 nM), was 50-fold selective in relation to alpha(1) adrenoceptors and at least 250-fold over 5-HT(2A) and D(2) sites. On the basis of in vivo functional tests, 8-phenylpiperazinoethylamino (11), 8-(2'-methoxyphenylpiperazino)ethylamino (13), and 8-phenylpiperazinopropylamino (14) derivatives of 1,3-dimethyl-1H,3H-pyrimido[2,1-f]purine-2,4-dione were identified as potent pre- and postsynaptic 5-HT(1A) receptor antagonists. 1,3-Dimethyl-7-bromo-8-(phenylpiperazinopropylamino)-1H,3H-pyrimido[2,1-f]purine-2,4-dione (20) behaved like an agonist of presynaptic and as a partial agonist of postsynaptic 5-HT(1A) receptors and resembled ipsapirone in terms of functional intrinsic activity. It revealed marked anxiolytic-like activity in the Vogel test in rats, comparable to that of the reference drug diazepam, and exhibited antidepressant-like activity in the Porsolt test in rats. The sedative effect of 20, evaluated in the open field test in rats, appeared at doses twice as high as those inducing a minimal anxiolytic-like effect and was similar to the effects of diazepam.

Animals↗

The isolation of cDNA clones from cucumber (Cucumis sativus L.) floral buds coming from plants differing in sex.

In this study, we found flower cDNA clones which may be connected with the development of flower sex in cucumber. Two pairs of nearly-isogenic lines: gynoecious GY3 (FFMMGG) versus hermaphrodite HGY3 (FFmmGG) and monoecious B10 (ffMMGG) versus gynoecious 2gg (ffMMgg) were used for clone isolation. To obtain differentially-expressed clones, we applied the differential screening method. 454 clones from GY3 and 478 from B10 cDNA libraries were isolated. The results of RFLP analysis with 56 cDNA clones showed no clones which cosegregated with sex in cucumber. The 28 cDNA B10 and 33 cDNA GY3 clones isolated using the differential screening method were sequenced. Some of them seem to may play a role in cell differentiation or flower development. Among the 61 identified clones, 14 show high homology to plant proteins, although of unknown function. 11 show high homology to known proteins, and the possible function of some of them is discussed. For 3 clones, no significant similarity was found. The 31 clones displayed high homology to plant cDNA in EST database. The patterns of expression of five differential cDNA clones, 35GY3, 216GY3, 47GY3, 100B10 and 157B10, were analyzed in cucumber flower buds using in situ RT-PCR. The most interesting clone is 35GY3, because of its possible role in the inhibition of the development of male specific elements in the female cucumber flower.

Amino Acid Sequence↗

[Pathomechanism of hyperlipoproteinemia in chronic renal failure].

Lipid disorders are one of the known metabolic changes associated with chronic renal failure (CRF) [1, 2]. They are present as: hypertriglyceridemia--existed in 60% of CRF patients and hypercholesterolemia observed in 20-30% of people with this syndrome. These disorders, what was shown also in our own studies, are existing in different intensity in patients treated with maintenance haemodialysis [3], peritoneal dialysis [4] and after renal transplantation as well [5]. Mechanism of hypertriglyceridemia, despite over thirty years of studies, is still not finally elucidated. The opinion that it is a result of impaired triglyceride removal (due to decreased activities of both lipoprotein and hepatic lipases) is well documented, however the role of lipogenesis in its development is obscure [6, 7]. The reports concerning this problem contain contradictory data. In our studies performed several years ago we have shown that lipogenesis rate in white adipose tissue of uremic rats is significantly augmented [8, 9, 10] due to activation of free fatty acid synthase. Therefore, recently we paid once again our attention on the activity of this lipogenesis rate limiting enzyme responsible for the long term regulation. We measured its activity, protein abundance and mRNA level in liver and epididymal white adipose tissue of rats with surgically induced renal failure (two-stage subtotal nephrectomy). The results support the thesis that lipogenesis takes a part in a hypertriglyceridemia found in renal failure. There have been observed a significant increase in plasma triglyceride and VLDL concentrations in uremic animals and it was associated with the increase of FAS activity, FAS protein abundance and FAS mRNA. The results were similar in both studied tissues. Moreover, there have been also observed the increased activities of malic enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. All these enzymes participate in NADPH production, which is a necessary substrate for fatty acid biosynthesis [11, 12, 13]. Concluding, it appears that the rise in plasma triglyceride and VLDL concentrations observed in CRF rats is not only the result of increased liver and white adipose tissue lipogenesis rate. One has to remember, that these date are strictly original and enabling to elucidation further pathogenesis of hyperlipidemia in CRF. In the second set of experiments performed also in rats with experimentally induced CRF we have found that hypercholesterolemia observed in those animals is dependent on the significant activation of cholesterol synthase, induced by increased production of this enzyme (increment of protein abundance and synthase mRNA [14, 15]. Simultaneously, we have performed original studies on the diurnal rhythm of cholesterologenesis, showing that activity of this process is significantly augmented during whole twenty four hours [15]. Summarizing, one have to underline that our observations have important impact to the elucidation of lipid disturbances pathomechanism. Nevertheless further studies are necessary to establish how experimental data are corresponding with human pathology.

Humans↗

Subtelomeric rearrangements: results from FISH studies in 84 families with idiopathic mental retardation.

BACKGROUND: The etiology of mental retardation (MR) is unexplained in at least 50% of cases. Recently it was shown that subtle telomeric rearrangements may be a common cause of idiopathic mental retardation (IMR). MATERIAL/METHODS: We studied 84 families with IMR and unspecific clinical features suggesting chromosomal aberration, including 59 patients with moderate to severe MR and 24 with mild MR. One healthy father of three deceased, severely MR children was also included. Fluorescence in situ hybridization (FISH) using 41 subtelomeric probes (the Chromoprobe Multiprobe--T System) was performed in all patients. RESULTS: Ten (11.9%) subtle chromosome rearrangements were identified. Nine (10.7%) were subtelomeric abnormalities. Seven were familial, with six of paternal origin. All but one were products of parental balanced reciprocal translocation or inversion. Retrospective G-banding analysis showed that six of the nine rearrangements could be seen or suspected at the 450-550 band levels. Subtelomeric abnormalities were recognized in six patients with severe/moderate (including the father of children with severe MR) and in three with mild MR. CONCLUSIONS: Our results confirm previous findings on the importance of subtelomeric rearrangements in the etiology of MR. They also show the diagnostic utility of subtelomeric FISH in detecting subtle telomeric rearrangements in IMR cases. The high proportion of familial rearrangements emphasizes their importance for genetic counseling. FISH screening was more reliable and efficient in identifying subtle telomeric abnormalities than G-banding analysis. However, as many of the subtelomeric abnormalities could be detected in retrospect even at the 550 band level, high-resolution G-banding analysis should always precede subtelomere assay. This is important for a better estimation of the real frequency of cryptic subtelomeric abnormalities.

Chromosome Aberrations↗