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Biomedical subjects

E Keller

Publications and source records attributed to E Keller.

At least 109 records · Page 6Linked to original sources
PubMed1999

Growth retardation in Turner syndrome: aneuploidy, rather than specific gene loss, may explain growth failure.

The etiology of short stature (SST) in Turner syndrome (TS) is still a subject of speculation. A variety of hypotheses have been put forward, from SST as a result of increased intrauterine tissue pressure after fetal lymphedema to haploinsufficiency of a specific growth gene(s). These hypotheses have various statistical-auxological implications on the growth distribution in TS. Empirical research has provided no clear evidence for any of these theories, but the well known correlation between patients' and midparental height (MPH) could be established. The influence of undetected mosaic status has often been cited as a major problem in the investigation of growth in TS. However, an assessment of mosaic status (simultaneous analysis of karyotype and phenotype) and its effect on growth with inclusion of MPH has been not yet carried out for a large sample. The aim of this study was to evaluate growth and its complex relationship to mosaic status and MPH in TS. In a mixed cross-sectional and longitudinal study we retrospectively analyzed the auxological and clinical data of 447 patients with a pure loss of X-chromosomal material (n = 381 with 45,X0; n = 66 mosaics). The 447 patients were selected from a series of 609 consecutive patients with TS. To assess the effect of mosaic status on growth, we computed a bifactorial analysis of variance (phenotype, karyotype), including MPH as a covariate. In line with the mosaic hypothesis, we found a correlation between individual loss of X-chromosomal material and phenotypical expressivity. In contrast, no correlation was found with respect to growth. With respect to MPH, we found growth retardation (GR) even in those patients with "normal" height above the third percentile (-2 or more SD score). The interindividual variance of GR in TS (comparable to growth variance in the normal population) seems to be unrelated to other TS-specific factors (e.g. mosaic status or single gene loss). Instead, both interindividual variance and the global growth shift distribution are best explained by the presence of an unspecific aneuploidic effect. Furthermore, consideration of patient height in relation to MPH should lead to a better understanding of the nature of GR in TS than the commonly used, strictly qualitative definition of SST.

Adolescent↗
PubMed1999

Predictive value of human leukocyte antigen class II typing for the development of islet autoantibodies and insulin-dependent diabetes postpartum in women with gestational diabetes.

Gestational diabetes mellitus (GDM) is a risk factor for the development of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus postpartum. To evaluate whether there is any association of human leukocyte antigen (HLA) class II alleles (DR and DQ) with GDM and the postpartum development of IDDM, we analyzed 184 women with GDM from Germany for HLA class II alleles, islet autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), and protein tyrosine phosphatase IA-2 autoantibodies (IA-2A), and the postpartum development of diabetes. No elevation in the frequency of any HLA class II alleles was observed in GDM patients compared to 254 nondiabetic unrelated subjects. DR3 allele frequency was significantly increased in 43 women with islet autoantibodies [corrected P value (Pc) = 0.02], in particular in those with GADA (Pc = 0.002), or in the 24 women who developed IDDM postpartum (Pc = 0.005). In women with GADA, DR4 and DQB1*0302 were significantly elevated (Pc = 0.009). Twenty-five (59.5%) islet antibody-positive women and 17 (74%) women who developed IDDM postpartum had a DR3- or DR4-containing genotype. The cumulative risk to develop IDDM within 2 yr postpartum in GDM women with either DR3 or DR4 was 22% compared to 7% in women without those alleles (P = 0.02) and rose to 50% in the DR3- or DR4-positive women who had required insulin during pregnancy (P = 0.006). Combining the determination of susceptible HLA alleles (DR3, DR4) with islet autoantibody measurement increased the sensitivity of identifying GDM women developing postpartum IDDM to 92%, but did not improve risk assessment above that achieved using GADA measurement alone, which was the strongest predictor of IDDM. These results indicate that women with GDM who have islet autoantibodies at delivery or develop IDDM postpartum have HLA alleles typical of late-onset type 1 diabetes, and that both HLA typing and islet antibodies can predict the development of postpartum IDDM.

Alleles↗
PubMed1999

Infantile fibromatosis of the neck with intracranial involvement: MR and CT findings.

CT and MR imaging studies were performed in a 3-year-old boy with infantile fibromatosis arising from the infratemporal fossa and extending into the middle cranial fossa. On CT scans, the lesion was hyperattenuating (44-49 Hounsfield units [HU]), enhancing significantly after application of contrast material (63-66 HU). The MR images showed a multilobulated lesion of heterogeneous signal intensity. The tumor was markedly hypointense on T2-weighted images and slightly hypointense on T1-weighted images relative to brain tissue, iso- or slightly hyperintense relative to tongue muscle on both T2- and T1-weighted images, and enhanced strongly after administration of gadopentetate dimeglumine.

Brain↗
PubMed1998

Effectiveness of treatments of depression in older ambulatory patients.

OBJECTIVE: To determine the effectiveness of acute-phase pharmacological and psychological treatments of depression in older ambulatory patients by systematically reviewing original research relevant to this topic. METHODS: Searches in MEDLINE and PsycINFO and manual reviews of bibliographies located 233 articles. Of these, 40 (37 different studies) met our 8 inclusion criteria: original research, written in English or French, subjects 55 years and older, diagnosis of depression, outpatient or community setting, prospective controlled study design, acute-phase pharmacological or psychological treatment, and outcome measure of depression. Two independent reviewers assessed the methodological quality of each article using a standard form and a quality score was computed. Quantitative data on levels of depression at the end of treatment were abstracted. Results were grouped by specific treatment comparison (type of treatment and type of control group). For comparisons that used the Hamilton Depression Rating Scale, we computed mean posttreatment differences. Effect sizes were computed from the Hamilton Depression Rating Scale or an alternative scale. RESULTS: In studies that compared active drugs with placebo, the heterocyclic drugs significantly reduced the posttreatment Hamilton Depression Rating Scale score (mean difference, -5.78; 95% confidence interval, -8.31 to -3.25); other drugs had smaller effects. In studies that compared active drugs, there were no significant differences overall between different classes of drugs; selective serotonin reuptake inhibitors appeared to be as effective as heterocyclic drugs. Rational psychological treatments performed significantly better than no treatment (mean posttreatment Hamilton Depression Rating Scale difference, -7.25; 95% confidence interval, -10.10 to -4.40) but not significantly better than that for controls who received similar attention. Adjustment for the study quality score did not affect these results. CONCLUSIONS: Based on comparisons with untreated controls, heterocyclic antidepressants and rational psychological therapies appear to be the most effective treatments for older ambulatory patients with mild to moderate depression. Based on drug-drug comparisons, selective serotonin reuptake inhibitors appear to be as effective as heterocyclic drugs. However, overall, the magnitude of the treatment effects is modest. Limitations in the quantity and quality of appropriate studies suggest a sober approach to treatment in this population.

Acute Disease↗
PubMed1998

The Nuclear Receptor Resource: a growing family.

Last year, the original Glucocorticoid Receptor Resource was expanded into a comprehensive project: the Nuclear Receptor Resource (NRR, http:// nrr.georgetown.edu/nrr/nrr.html ). The NRR has since been offering comprehensive information on nuclear receptor structure and function, as well as general facts of interest to the scientific community on meetings, funding and employment opportunities. The project now includes individual resources as part of a network which integrates information on glucocorticoid, androgen, mineralocorticoid, thyroid hormone, Vitamin D and peroxisome-proliferator activated receptors. Many investigators have joined the NRR network by filling the Who is who? form available in the NRR home page. This has facilitated communication among scientists in the field and dissemination of data nor otherwise published. Because several investigators have contacted NRR authors over the past few months asking for advice and materials for educational purposes, we have recently decided to include in our project an educational resource on nuclear receptors termed the 'Graphics Library'. The input and suggestions of NRR users do shape the future direction of the project, so we encourage user to give us feedback.

Computer Communication Networks↗
PubMed1998

Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements.

OBJECTIVES: To determine the motor cortex degeneration in patients with amyotrophic lateral sclerosis (ALS) using proton magnetic resonance spectroscopy, and to prove that proton magnetic resonance spectroscopy is suited to monitor the course of disease with follow-up examinations. MATERIALS AND METHODS: We studied 33 patients with ALS whose conditions were diagnosed according to the El Escorial World Federation of Neurology criteria. Nine patients with ALS were followed up for up to 2 years. The control group included 20 healthy volunteers and 4 patients with multifocal motor neuropathy. Proton magnetic resonance spectroscopy determined levels of the brain metabolites N-acetylaspartate (NAA), choline, inositol-containing compounds, glutamate/glutamine, and phosphocreatine. RESULTS: Patients with ALS showed a significant reduction in the NAA-choline (P <.001) and NAA-phosphocreatine (P <.005) metabolite ratios and significantly elevated choline-phosphocreatine (P <.005) ratios compared with controls. Inositol-phosphocreatine ratios were also elevated in case patients, but the increase was less pronounced (P <.05). No differences in glutamate/glutamine-phosphocreatine ratios were detected between case patients and controls. An analysis of subgroups demonstrated less significant differences in NAA-choline metabolite ratios (P<.05), even in patients with pure lower motor neuron syndrome (suspected ALS). No changes in metabolite T1 and T2 relaxation times were observed. Patients with multifocal motor neuropathy showed normal metabolic ratios. Progressive alterations in affected metabolite ratios could be documented in the follow-up examinations. CONCLUSIONS: Spectroscopic changes in the motor cortices of patients with ALS correspond with a reduction in levels of NAA and an elevation in levels of choline and inositol compounds. Since NAA is exclusively expressed in neurons, the observed decrease of NAA reflects neuronal loss or dysfunction. Inositol and choline are associated with plasma membrane metabolism, so the release of these compounds may be related to membrane disorders.

Adult↗
PubMed1998

Moderate hypothermia and brain temperature in patients with severe middle cerebral artery infarction.

Elevated temperature is known to facilitate neuronal injury after ischemia. After head injury a gradient between temperature and body temperature of up to 3 degrees C higher in the brain has been reported. Hypothermia may limit some of the deleterious metabolic consequences of such increased temperature. In 20 patients who had suffered severe ischemic stroke in the middle cerebral artery (MCA) territory, intracerebral temperature combined with ICP monitoring was recorded using two different thermocouples, with epidural, and parenchymatous measurements. Mild hypothermia was induced using cooling blankets. Patients were kept at 33 degrees C core temperature for 48 to 72 hours. In all patients brain temperature exceeded body-core temperature by at least up to 1 degree C (range 1.0-2.1 degrees C). Systemic cooling was effective and sustained hypothermic (33-34 degrees C) brain temperatures. With mild hypothermia critically elevated ICP values could be controlled. 12 patients survived the hemispheric stroke with a mean Barthel index of 70. Severe side effects of hypothermia were not detected. After MCA stroke, human intracerebral temperature is higher than central body-core temperature. Mild hypothermia in the treatment of severe cerebral ischemia using cooling blankets is safe and does not lead to severe side effects. Mild hypothermia can help to control critically elevated ICP values in severe space-occupying stroke and may improve clinical outcome in these patients.

Adult↗
PubMed1998

Spondyloenchondrodysplasia: several phenotypes--the same syndrome.

We present details of a dwarfing skeletal dysplasia in two boys. Radiographs show multiple enchondromas of tubular and flat bones together with abnormalities of the spinal column. Clinical, laboratory and radiological findings enable this entity to be grouped within the spectrum of enchondromatoses with vertebral changes. A literature review suggests heterogeneity of this group of conditions.

Adolescent↗
PubMed1998

Evaluation and optimisation of separation buffers for the determination of corticosteroids with micellar electrokinetic capillary chromatography (MECC).

Separation buffers for the determination of the corticosteroids cortisone, hydrocortisone, prednisone and prednisolone with micellar electrokinetic chromatography were developed with respect to separation efficacy and the migration times, depending on the type and the concentration of the organic modifier acetonitrile as well as on the addition of gamma-cyclodextrin. The buffer containing 50 mM SDS and 16% (v/v) acetonitrile enables the rapid profiling of prednisolone together with cortisone and prednisone. Addition of gamma-cyclodextrin alters the elution sequence, but does not further enhance resolution of the corticosteroids. Baseline separation at long migration times for cortisone, hydrocortisone, prednisone and prednisolone is achieved with a buffer containing 50 mM each of SDS, dehydrocholic acid sodium salt and glycodeoxycholic acid sodium salt.

Acetonitriles↗
PubMed1998

A vigorous virus-specific CD4+ T cell response may contribute to the association of HLA-DR13 with viral clearance in hepatitis B.

A strong virus-specific CD4+ and CD8+ T lymphocyte response to hepatitis B virus (HBV) has been associated with viral clearance, but little is known about factors determining the individual's ability to mount such a T cell response. Recently a strong association between the HLA class II allele DR13 and a self-limited course of HBV infection has been described. In the present study of 33 patients with acute hepatitis B we show that individuals carrying HLA-DR13 mount a more vigorous CD4+ T cell response to HBV core (5706 ct/min (25th/75th percentile 3239 ct/min; 10,552 ct/min)) than patients without HLA-DR 13 (1365 ct/min (490 ct/min; 5334 ct/min); P = 0.006). However, peptide epitopes aa 50-69, aa 61-85, and aa 81-105 were recognized most frequently by both patient groups. Moreover, among 14 HBV core-specific CD4+ T cell clones from two patients with HLA-DR13, only one T cell clone was HLA-DR13-restricted. Our data suggest that the beneficial effect of the HLA-DR13 alleles on the outcome of HBV infection could be explained by a more vigorous HBV core-specific CD4+ T cell response, which may either be due to more proficient antigen presentation by the HLA-DR13 molecules themselves or a linked polymorphism in a neighbouring immunoregulatory gene.

Acute Disease↗
PubMed1998

Inflammatory bowel disease: no association between allele combinations of the interleukin (IL) I beta and IL-I receptor antagonist gene polymorphisms.

BACKGROUND: Interleukin 1 (IL-1) and its physiological antagonist interleukin-1 receptor antagonist (IL-1 ra) play a crucial role in the pathogenesis of inflammatory bowel disease. Polymorphisms in the genes coding for these cytokines, the restriction enzyme TaqI polymorphism for IL-1 beta and the variable number of tandem repeats (VNTR) polymorphism for IL-1 ra, have been shown to influence cytokine synthesis in vitro. Recently, an association has been described for distinct allele combinations of these two polymorphisms in patients with ulcerative colitis and with Crohn's disease but not in healthy control subjects. METHODS: We studied 56 patients with ulcerative colitis, 64 patients with Crohn's disease and 196 healthy control subjects. All were unrelated Caucasians of European ancestry. After polymerase chain reaction (PCR) the amplification products were analysed on agarose gels. For the IL-1 beta polymorphism the PCR product was additionally digested using the restriction enzyme TaqI. RESULTS: The allele and genotype frequencies as well as the carriage rates of the IL-1 beta TaqI polymorphism in healthy control subjects were in agreement with previous findings in other populations. Allele and genotype frequencies of the IL-1 beta polymorphism were not different in inflammatory bowel disease patients compared with healthy control subjects. Comparing allele combinations of both polymorphisms no association could be identified either within healthy control subjects or in the groups of patients with ulcerative colitis or Crohn's disease. CONCLUSION: Thus, we could not confirm the results of a previous study reporting an association between the IL-1ra and IL-1 beta gene polymorphisms in patients with inflammatory bowel disease.

Adult↗
PubMed1998

[A rational study of the great abdominal veins using 2D-TOF- and turbo-spin-echo sequences].

PURPOSE: Development of a fast and reliable protocol for the detection and exclusion of abdominal venous thrombosis with an optimised T2-TSE- and 2D-TOF sequence. MATERIAL AND METHOD: Evaluation of the flow-void phenomenon with a flow phantom on a 1.5 and 0.5 Tesla system using different echo times. Examination of 22 patients with suspected abdominal shunt- or abdominal vein-thrombosis with a optimum T2-TSE- and 2D-TOF sequence with a 1.5 or 0.5 Tesla system. Confirmation of thrombosis with contrast-enhanced computed tomography or digital subtraction angiography. RESULTS: The most effective combination of strong flow-void phenomena, signal/noise ratio and scan time was found with the following parameters: TE 120 ms, TR 2000 ms, 5 mm slice gap. In the patient group two complete and two partial thromboses were diagnosed with both sequences. One wrong positive thrombosis occurred in a stenotic anastomosis with the 2D-inflow sequence. CONCLUSION: With optimum parameters the T2-TSE sequence produces a strong "flow-void" phenomenon suitable for "black-blood"-MRA. The use of this sequence alone or in combination with 2D-inflow MRA, if "bright-blood" MRA is recommended, allows a reliable evaluation of thrombosis in abdominal veins without high-tech MRA equipment and contrast media.

Abdomen↗
PubMed1998

[31P-mr spectroscopy of peripheral skeletal musculature under load: demonstration of normal energy metabolites compared with metabolic muscle diseases].

PURPOSE: 31P-MR spectroscopy of skeletal muscle under exercise was used to obtain the range of normal variation and comparison was made for different neuromuscular diseases. METHODS: 41 examinations of 24 volunteers and 41 investigations in 35 patients were performed on 1.5 T MR systems (Gyroscan 515 und S15/ACSII, Philips). Localised 31P-MR spectra of the calf muscle were obtained in time series with a resolution of 12 s. RESULTS: Two types of muscle energy metabolism were identified from the pattern of spectroscopic time course in volunteers: While the first group was characterised by a remarkable decline to lower pH values during exercise, the second group showed only small pH shifts (minimum pH: 6.48 +/- 0.13 vs 6.87 +/- 0.07, p < 10(-6)) although comparable workload conditions were maintained. The pH-values correlated well with blood lactate analysis. Patients with metabolic disorders and chronic fatigue syndrome (CFS) showed decreased resting values of PCr/(PCr + Pi) and increased pH levels during exercise. PCr recovery was significantly delayed (0.31 vs 0.65 min-1, p < 0.00005) in metabolic muscle disorders but was normal in CFS patients. CONCLUSION: Findings in volunteers indicate utilisation of different metabolic pathways which seems to be related to the fibre type composition of muscle. Reduced resting levels for PCr/(PCr + Pi), altered pH time courses, and decreased PCr recovery seem to be helpful indicators for diagnosis of metabolic muscle disorders.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1998

[Improved diagnosis of early cerebral infarct by the combined use of diffusion and perfusion].

PURPOSE: To evaluate the feasibility and the diagnostic efficacy of multislice diffusion-weighted and perfusion imaging in addition to FLAIR-TSE, T2w-GraSE and MR-angiography in the diagnosis of acute stroke. METHODS: 18 patients with acute stroke were examined at 1.5 Tesla (Gyroscan ACS-NT, Philips Medical Systems) within 6 (n = 9) and 6-48 (n = 9) hours, respectively, and followed at regular intervals. For diffusion imaging we used a multislice multishot EPI-SE sequence with navigator echo correction and cardiac gating. Perfusion imaging was done by means of a FFE-EPI sequence after bolus injection of Gd-DTPA. RESULTS: The diagnostic value of diffusion-weighted and perfusion imaging was significantly higher compared with FLAIR-TSE (p = 0.0023) and GraSE (p = 0.0012) during the first 6 hours. With FLAIR-TSE and GraSE first pathologic changes were seen after 4 hours. We detected perfusion deficit (rCBV < 10%) and a corresponding drop of the ADC in all infarcts larger than 1 cm in diameter. Within the area of low rCBV the combined analysis of diffusion and perfusion imaging allows to identify an infarct region with characteristics of a penumbra and one with characteristics of the infarct core. TTP was increased in the surrounding tissue. However, parts of this area were rarely included in the infarct. The final extension of the untreated infarct, as revealed by computed tomography, corresponded well to the perfusion deficit. CONCLUSIONS: Early ischaemic cerebral infarcts can be diagnosed with diffusion and perfusion imaging before pathological changes are visualized with other imaging modalities. The combined use may allow to distinguish the infarct core from surrounding, potentially salvageable tissue.

Adult↗
PubMed1998

[Diffusion-weighted MR tomography: navigated multi-shot SE-EPI technique for clinical use].

PURPOSE: Evaluation of a navigated multi-shot SE EPI sequence for routine clinical use in MR diffusion imaging. METHODS: We compared a multi-shot SE EPI sequence with the conventional SE sequence as well as with a single-shot SE EPI sequence on a standard 1.5 Tesla MR-scanner (ACS-NT, Philips Medical Systems) with a conventional gradient system (10 mT/m). Image quality and the reproducibility of the apparent diffusion coefficient were analysed with phantoms and with healthy volunteers. The diffusion coefficients of different brain areas were determined in a group of twenty volunteers. RESULTS: The multi-shot SE EPI sequence showed considerably shorter measurement times and smaller motion artifacts than the SE sequence and was less sensitive to susceptibility artifacts than the single-shot version. The reproducibility of the diffusion coefficients was better than 10%. CONCLUSION: The navigated multi-shot SE technique is more practicable and meaningful than the SE and the single-shot SE EPI techniques on a standard 1.5 Tesla MR-scanner with a conventional gradient system. In our opinion it is now the best method for diffusion imaging and should be preferred in clinical use. The determination of diffusion coefficients yields reliable results and characteristic values for different tissue can be obtained.

Adult↗