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Biomedical subjects

E Keller

Publications and source records attributed to E Keller.

At least 19 recordsLinked to original sources
PubMed2002

[1H-MR Spectroscopy of brain tumors in the course of radiation therapy: Use of fast spectroscopic imaging and single-voxel spectroscopy for diagnosing recurrence].

PURPOSE: To improve differential diagnosis of residual or recurrent tumor vs. tissue necrosis in the course of radiation therapy of neurosurgically-treated brain tumors by application of fast (1)H-MR spectroscopic imaging in combination with single-voxel spectroscopy (SVS). METHODS: 54 patients after with malignant brain tumor (44 cases of glioblastoma, 10 other high-grade gliomas) were examined post-surgically in a total of 140 proton MRS examinations in the course of radiotherapy and in follow-up controls. Fast SI acquisition was performed as single-slice or double-slice TSI sequence with 32 x 32 phase encodings within 11 or 15 minutes, respectively. SVS with TR/TE 2000/272 ms yielded relative metabolite ratios, and in 15 patients the time courses of the absolute concentrations of brain metabolites were also determined. RESULTS: In the group of 44 patients that could be tracked by MRS until therapy completion, TSI localized in 23 patients a persistent or newly arisen distinct choline accumulation indicating residual or recurrent tumor after radiation therapy. In all these cases MRS diagnosis was confirmed histologically or by short-term follow-up. However, in 6 of 15 patients showing a normal choline pattern in the TSI acquisition, tumor recurrence appeared within three months. SVS provided early recognition of recurrent tumor when detecting characteristic alterations of metabolite concentrations oin therapy follow-up. CONCLUSION: TSI and SVS represent complementary MRS techniques and are able to diagnose tumor recurrence early and unambiguously in cases where focal choline accumulation is detected.

Adult↗
PubMed2002

Favorable final height outcome in girls with Ullrich-Turner syndrome treated with low-dose growth hormone together with oxandrolone despite starting treatment after 10 years of age.

The objective of this study was to find out whether moderate doses of growth hormone (GH) in combination with oxandrolone (Ox) and late initiation of puberty could improve adult height even in relatively old patients with Ullrich-Turner syndrome (UTS). Ninety-one patients with UTS were randomly assigned to receive either GH alone (Saizen, Ares-Serono, Geneva) 18 IU/m2/week (0.2 mg/kg/week) by daily s.c. injections (group GH) or a combination of GH and Ox 0.1 mg/kg/day p.o. (group GH + Ox). Prior to treatment mean age was 10.2 years (GH) and 10.5 years (GH + Ox), mean projected adult height (PAH) was 146.4 cm (GH) and 146.7 cm (GH + Ox). During year 2 the GH dose was increased in the GH group to 24 and later to 28 IU/m2/week (0.27 mg and later 0.31 mg/kg/week). In group GH + Ox, the Ox dose was reduced to 0.05 mg/kg/day after the first 12 months of therapy, and during the last treatment years the GH dose was raised to 24-28 IU/m2/week (0.27-0.31 mg/kg/week) due to declining growth promotion. Some of the patients of group GH were later given Ox in addition to GH because of waning growth velocity, whereas some of the patients of group GH + Ox were taken off Ox due to virilizing side-effects of the high Ox dose, thus making up a third group of patients: group GH + transient Ox. Puberty was induced at a mean age of 14.9 years. In group GH + Ox, cumulative growth during 5 years of therapy was twice the growth anticipated from standards of untreated patients with UTS. Forty-seven patients are now near or at final height: in group GH (n = 7), mean final height was 151.7 cm (PAH 148.1 cm, gain 3.6 cm); in group GH + Ox (n = 15), 155.1 cm (PAH 147.2 cm, gain 7.9 cm); and in group GH + transient Ox (n = 25), 152.8 cm (PAH 146.4 cm, gain 6.4 cm). These results should be regarded as an underestimate of true final height since some the patients are still growing. Moderate doses of GH plus Ox and late induction of puberty definitely improved final height even in patients with UTS treated relatively late.

Adolescent↗
PubMed2001

[Effect of retinoic acid on the cytogenetic remission in the first chronic phase of chronic myeloid leukemia treated with interferon].

Cytogenetic responses of 11 chronic myeloid leukemic (CML) patients during the first chronic phase, treated with the combination of all-trans retinoic acid (ATRA) + interferon (IFN) were compared to 9 other CML patients of phase one, treated with interferon monotherapy. Metaphase and interphase cytogenetics and a semiquantitative polymerase chain reaction (PCR) were used to evaluate the cytogenetic responses. Two of the 11 patients in the ATRA + interferon treated group were withdrawn, one of them because of interferon intolerance, and the other because of compliance failure. Among the 9 ATRA + interferon treated patients 6 major cytogenetic responses could be detected and 3 of them were complete. Of the 9 patients treated with IFN monotherapy only 2 major cytogenetic responses could be registered. No severe adverse effects were observed. The first results suggest that the ATRA + interferon combination may be superior in achieving cytogenetic remission in the first chronic phase of CML.

Adult↗
PubMed2001

Decrease of N-acetylaspartate in the MTL correlates with cognitive decline of AD patients.

In this (1)H-MRS follow-up study of the medial temporal lobe (MTL) in patients with AD, the authors report a correlation of N-acetylaspartate (NAA)/creatine (Cr) with cognitive decline. Severely progressed patients showed a reduction, whereas stable or mildly progressed subjects showed a slight increase of NAA/Cr. The reduction of NAA/Cr in the MTL represents a correlate of cognitive deterioration in AD, whereas it is of limited use to detect subtle changes over time in clinically stable patients.

Aged↗
PubMed2001

Maternal isochromosome 7q and paternal isochromosome 7p in a boy with growth retardation.

A 12-year 9-month-old boy with postnatal growth retardation, normal psychomotor development, and minor anomalies that included a triangular-shaped face, small nose, and narrow and high-arched palate is reported. The constitutional karyotype was 46,XY,i(7)(p10),i(7)(q10). Molecular investigations revealed the presence of a maternal isodisomy 7q and a paternal isodisomy 7p. The clinical and molecular findings are notably congruent with a recently reported case and support the hypothesis of one or more maternally imprinted genes located on the long arm of chromosomes 7 that regulate, in particular, postnatal growth.

Adolescent↗
PubMed2001

A light stabilizer Tinuvin 770-induced toxic injury of adult rat cardiac myocytes.

Tinuvin 770/bis(2,2,6,6-tetramethyl-4-piperidinyl)sebacate is a worldwide used light stabilizer for plastic materials like polyolefins. Tinuvin 770 is a biologically active component of polypropylene tubes. Glossmann and his study group managed to extract this compound by aqueous or organic solvents from laboratory plastic tubes, and propose that Tinuvin 770 is a potent blocker of L-type Ca(2+)-channel through the phenylalkylamine and benzothiazepine-selective drug binding domains of the alpha(1) subunit of the receptor [Proc. Natl. Acad. Sci. U.S.A. 90 (1993) 9523]. We examined the direct morphological effect of Tinuvin 770 in give 25nmol, 0, 30, 60, 120 minute exposure time in isolated cardiomyocytes from adult rats. Incubation of myocytes with Tinuvin resulted in a progressive decline of rod-shaped and viable cells. It was accompanied by an increase in number of hypercontracted myocytes with microbleb formation compared to control and depletion of ATP level. In summary, our results demonstrate that plasma membrane damage and hypercontraction are manifestations of Tinuvin-induced injury of isolated cardiomyocytes.

Animals↗
PubMed2001

Phenotype assignment in symptomatic female carriers of X-linked adrenoleukodystrophy.

However, only very few studies have systematically investigated the extent and distribution of nervous and endocrine system involvement in female carriers of X-ALD. To define the phenotype in symptomatic female carriers of X-ALD we performed a prospective study including eight symptomatic women who were followed for a mean period of 3.4+/-1.8 years (range 1-6) using standardized clinical examination protocols, magnetic resonance imaging and spectroscopy, evoked potential studies including visual, brainstem auditory, somatosensory and magnetic evoked potentials, neurographic recordings and endocrine studies. Spastic paraparesis and decreased vibration sense in the lower extremities were the most frequent clinical findings. Slightly hyperintense symmetric parieto-occipital white matter lesions on magnetic resonance imaging were detectable in two of seven cases, and the N-acetylaspartate/choline ratios on magnetic resonance spectroscopy were decreased in three of seven patients. P40 latencies were abnormal in all patients, and central motor conduction times to the lower extremities in seven of eight patients. Prolonged latencies of brainstem auditory evoked potential waves III-V or interpeak latencies of waves I-III, I-V and III-V were detectable in all patients. The degree of walking impairment was positively correlated with the duration of clinical disease (r=0.58, P < 0.05) and inversely correlated with the N-acetylaspartate/choline ratios (r=0.85; P < 0.05). Neurographic recordings revealed only subtle abnormalities, suggesting that nervous system involvement in symptomatic female carriers of X-ALD is confined mainly to the central nervous system. No evidence of adrenal insufficiency was detected in any of the patients.

Adrenal Insufficiency↗
PubMed2001

Serum leptin in formerly small-for-gestational-age children during adolescence: relationship to gender, puberty, body composition, insulin sensitivity, creatinine, and serum uric acid.

Serum leptin levels reflect body fat mass (FM), and have been described to be related to serum uric acid levels in adult type 2 diabetic and healthy subjects. We therefore aimed to evaluate the interrelationship between leptin and markers of the metabolic syndrome by studying serum leptin concentration, body mass index (BMI), percent body fat (Fat%), total fat mass (FM), sum of skinfolds (SS), triglycerides (TG), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose, insulin, calculated insulin resistance (HOMA), creatinine (CR), and uric acid (UA) concentration in 50 former small-for-gestational-age (SGA) children and 21 infants born adequate for gestational age (AGA) at the time of mid-puberty. Our data confirm previous results showing a positive association between leptin and body fatness, and female gender. Twelve children with impaired glucose tolerance (IGT) had higher UA levels than subjects with normal glucose tolerance (NGT) (5.1 +/- 1.1 v 4.2 +/- 1.2 mg/dL, P <.05), and showed the strongest relation between serum leptin and UA (r =.76, P <.001). Multiple regression analyses demonstrated that gender, estimates of total body adiposity (Fat% and SS), birth weight (BW), gestational age (GA), stimulated glucose and insulin, and serum UA are independently associated with serum leptin concentration in former SGA children with dysglycemia (R(2) =.89, P <.001). A long-term effect of intrauterine growth restriction on body fatness, metabolic syndrome, and serum leptin levels is suggested.

Adolescent↗
PubMed2001

[Creutzfeldt-Jakob disease: value of MRI].

PURPOSE: To define the role of MRI in the diagnosis of Creutzfeldt-Jakob disease (CJD). METHODS: 14 patients with suspected CJD were studied within 3 years. MRI findings were correlated with WHO established diagnostic criteria (clinical findings, EEG, CSF with 14-3-3 protein assay). RESULTS: 12 patients had CJD. One patient each suffered from Hashimoto's encephalitis and ALS dementia complex, respectively. Nine of 12 CJD patients had increased signal intensity of the striatum (n = 8), pulvinar thalami (n = 5) and/or cerebellar and cerebral cortex (n = 3), respectively. Signal intensity was most pronounced on FLAIR sequences; six patients were studied with diffusion-weighted MRI and showed impaired diffusion in these areas. Both patients without CJD did not show the abovementioned signal changes (sensitivity 75%, specificity and positive predictive value 100%, respectively). CONCLUSION: If patients with suspected CJD are studied with FLAIR and diffusion-weighted sequences, this disorder can reliably be proven or ruled out. Typical MRI findings narrow down the differential diagnosis and should be included in the WHO diagnostic criteria.

Adult↗
PubMed2001

Estimation of cerebral oxygenation and hemodynamics in cerebral vasospasm using indocyaningreen dye dilution and near infrared spectroscopy: a case report.

Changes in cerebral hemodynamics and oxygenation patterns in cerebral vasospasm might be underestimated if transcranial doppler sonography and angiography findings are considered singularly. This report describes preliminary findings in further development of a noninvasive method that estimates regional cerebral oxygenation and perfusion. A 50-year-old patient suffering from cerebral vasospasm after subarachnoid hemorrhage before and after superselective papaverine infusion was examined. Measurements were taken by using a technique combining indocyaningreen dye dilution and near infrared spectroscopy. Our first results suggest that the technique could be suitable for estimation of cerebral hemodynamics. This noninvasive technique can be performed at the bedside and in special environments, such as neurocritical care units. It seems to be safe, easy to perform, and less time-consuming than conventional techniques. Combination of indocyaningreen dye dilution and near infrared spectroscopy might become a powerful tool in the detection and treatment of cerebral vasospasm causing delayed cerebral ischemic deficit. Further larger-scale investigations are necessary to evaluate the diagnostic accuracy of this technique. Our preliminary observations however, based on measurements before and after superselective papaverine infusion in vasospastic vessels, helped to clarify the influence of extracerebral contamination on the cerebral near infrared spectroscopy signal in the adult head.

Brain Chemistry↗
PubMed2001

Computer-guided, population-based screening system for growth disorders (CrescNet) and on-line generation of normative data for growth and development.

The mean age at which the diagnosis of growth disorders such as Turner's syndrome, growth hormone (GH) deficiency or true GH-dependent gigantism is established is still rather late in many countries around the world. In addition, the question of secular trends in a given population and the rate at which childhood obesity is increasing in industrialized countries make it mandatory to establish a time-adapted system to develop percentiles for body height, weight and body mass index (BMI) and also to develop a screening system for growth disorders. In 1998 we established a network, now involving more than 160 paediatric practices in Germany and seven paediatric endocrinology departments. Paediatricians record heights, weights and growth velocities of all children in their care and systematically feed the data into the database at our centre usually by mailing formatted, structured data tickets. Data are then continuously analysed at the centre and the paediatricians in the network are informed immediately about their individual patients' growth situations via phone or E-mail (feedback system). Regular annual conferences including structured reports, scientific presentations and discussion groups are organized for all participants at our centre. By May 2001, the data of 83,721 children and adolescents had been analysed. The mean values for height were 1-1.5 cm higher than the mean values in the German Synthetic Growth Curve, which serves as an internal standard. However, and most importantly, in comparison with the internal standard and historical normative data from Germany and Switzerland, there is a continuous increase in the 97th percentile for weight and BMI, while the third percentile remains unchanged. In addition, many children with short stature and tall stature due to a variety of endocrine disorders and genetic diseases which had not been diagnosed previously are now being identified. In conclusion, the databank allows for a continuous adaptation of normative curves based on a large number of children in a given population, i.e. eastern Germany. Secondly, the system allows for detection of pathological growth curves and is already serving to diagnose growth disorders in a defined population in a systematic way.

Adolescent↗
PubMed2001

The treadmill exhausting test is not suitable for screening of growth hormone deficiency!

BACKGROUND/METHOD: We compared the growth hormone response to a modified exercise test--the treadmill exhausting test--to pharmacological stimulation tests in 77 children with short stature. Each child underwent the treadmill test to individual exhaustion and at least one pharmacological test for GH stimulation. To determine the point of individual exhaustion, the heart rate, workload and oxygen consumption were measured. RESULTS: The mean +/- SEM peak GH concentration (ng/ml) in 47 small, normally growing children (group 1) was 16.1 +/- 1.3 in the pharmacological tests vs. 5.0 +/- 0.6 after a treadmill exhausting test. Thirty children with GH deficiency (group 2) had mean +/- SEM peak GH concentrations (ng/ml) of 5.5 +/- 0.5 in the pharmacological tests and 4.1 +/- 0.7 after physical exercise. The groups differed significantly in the pharmacological tests (p < 0.001) but not in the exhausting test. We found a 90% sensitivity but only a 11% specificity for the treadmill exhausting test compared to the diagnosis obtained by pharmacological testing. CONCLUSION: We do not recommend the treadmill exhausting test in clinical practice of pediatric endocrinology at all.

Adolescent↗
PubMed2001

Isolated GH deficiency with dominant inheritance: new mutations, new insights.

Autosomal dominantly inherited isolated GH deficiency is caused by mutations of GH-1 that alter the normal structure of GH. We studied 16 familial cases and 1 sporadic case with isolated GH deficiency type II from 1 Dutch and 4 German families by direct sequencing of PCR-amplified genomic DNA and ectopic transcript analysis of lymphocyte mRNA. In addition, the clinical data of the affected individuals were analyzed. Two previously reported mutations and 1 novel splice site mutation in intron III of GH-1 (+1G to C and +1G to A; new, +2T to C) were detected that cause exon 3 skipping. We also discovered a novel G6191 to T missense mutation in exon 4 of GH-1 that changes valine 110, which is highly conserved in mammalian and several nonmammalian GH, to phenylalanine. Splicing of the primary RNA transcript was not affected by this mutation, which is very likely to alter the normal GH structure at the protein level. The onset of growth failure was earlier, and the degree was more severe in affected children with GH-1 splice site mutations compared with those in children with the GH-1 missense mutation. In addition, the severity of the phenotype was variable, even within the same family. The age at diagnosis was between 0.8-9.6 yr (median, 5.1 yr); height at diagnosis was between -2.5 and -8.1 SD score (median, -4.0). Most of the children were lean at diagnosis, with a body mass index ranging from -1.7 to +3.3 SD score (median, -0.5). The 5 affected adults had final heights between -1.8 and -4.5 SD score (median, -3.6), centripetal obesity, and muscular hypotrophy. Before therapy, IGF-I and IGF-binding protein-3 serum levels of all affected children were severely diminished (<<5th percentiles for age). The maximum GH peak in a total of 25 stimulation tests was between 0.1-5.0 microg/liter (median, 0.9), indicating severe GH deficiency. The height of the adenohypophysis studied by magnetic resonance imaging was normal in 2 affected children and mildly decreased in 2 others. Substitution with GH resulted in good catch-up growth in all treated children. Children with severe GH and IGF-I deficiencies, but normal size of the adenohypophysis should be examined for GH-1 splice site and missense mutations. The observed discrepancy between the very homogeneous hormone data proving severe GH and IGF-I deficiencies and the high variability of growth failure even within the same family suggests that the onset and predominance of GH-dependent growth during infancy are individually different and modified by as yet unknown factors.

Age Determination by Skeleton↗
PubMed2001

A new and accurate prediction model for growth response to growth hormone treatment in children with growth hormone deficiency.

OBJECTIVE: To identify parameters which predict individual growth response to recombinant human GH (rhGH) therapy and to combine these parameters in a prediction model. DESIGN: Fifty-eight prepubertal patients with GH deficiency (17 females) participated in this prospective multicenter trial with 1 year of follow-up. METHODS: Auxological measurements, parameters of GH status and markers of bone metabolism were measured at baseline and at 1, 3 and 6 months after the start of rhGH treatment. Correlations with height velocity during the first 12 months of treatment (HV+12) were calculated. Prediction models were derived by multiple regression analysis. RESULTS: The model which best predicted HV+12 combined the following parameters: pretreatment bone age retardation as a fraction of chronological age, pretreatment serum levels of IGF-I, urinary levels of deoxypyridinoline (a marker of bone resorption) after 1 month of treatment and height velocity after 3 months of treatment. This model explained 89% of the variation in HV+12 with a standard deviation of the residuals of 0.93 cm/year. Defining successful rhGH therapy as a doubling of pretreatment height velocity, the model had a specificity of 90% and a sensitivity of 100% in predicting therapeutic success. CONCLUSIONS: This model is an accurate and practicable tool to predict growth response in GH-deficient children. It may help to optimize rhGH therapy by individual dose adjustment and contribute to improved overall outcomes.

Adolescent↗
PubMed2001

Long-term administration of the HMG-CoA reductase inhibitor lovastatin in two patients with cholesteryl ester storage disease.

OBJECTIVE: In order to suppress de novo cholesterol and VLDL biosynthesis, a long-term therapy trial with lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, was initiated in two patients with cholesteryl ester storage disease (CESD), and concentrations of plasma lipids were monitored over a period of 9 years. METHODS: We studied two male patients with enzymatically confirmed CESD in whom long-term lovastatin therapy (8 and 9 years) was begun at the age of 7 and 19 years. The diagnosis of CESD was confirmed by the measurement of human lysosomal acid lipase (hLAL) activity in cultured skin fibroblasts and leukocytes. Restriction fragment length polymorphism (RFLP) analysis revealed that both subjects are homozygotes for the common CESD splice site mutation. Levels of serum lipids and lipoproteins were measured yearly. RESULTS: During the first year, total serum cholesterol decreased from 317 to 201 mg/dl in Patient A and from 228 to 120 mg/dl in Patient B, due mainly to the reduction of low-density lipoprotein (LDL) cholesterol from 262 to 151 mg/dt in Patient A and from 166 to 66 mg/dl in Patient B. Accordingly, the LDL cholesterol : high density lipoprotein (HDL) cholesterol ratio was markedly reduced in both patients after one year of therapy. The treatment was continued and, after 9 years of further medication, low total cholesterol and LDL cholesterol levels were still maintained. CONCLUSIONS: The study demonstrates that HMG-CoA reductase inhibitors are well tolerated drugs during long-term treatment of CESD patients and may help to prevent the development of premature atherosclerosis.

Adult↗