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K Meyer

Publications and source records attributed to K Meyer.

At least 55 records · Page 3Linked to original sources
PubMed2001

FAB M4 and high CD14 surface expression is associated with high cellular resistance to Ara-C and daunorubicin: implications for clinical outcome in acute myeloid leukaemia.

In 145 adult patients diagnosed with non-M3 acute myeloid leukaemia (AML) the relevance of FAB-subtype and immunophenotype to in vitro cellular drug resistance towards the anthracyclines aclarubicin (Acla) and daunorubicin (Dau), and the nucleoside analogue cytarabine (Ara-C), as well as other antileukaemic drugs, was investigated using a 4-d MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. We demonstrate that high CD14 expression is highly significantly associated with high cellular Ara-C and Dau resistance in univariate as well as multivariate analyses. FAB subtypes with highest and lowest cellular Ara-C resistance were M4 and M5, respectively (P < 0.01, one-way anova), whereas FAB subtypes with highest and lowest cellular Dau resistance were M4 and M1, respectively (P < 0.01, one-way anova). By contrast, no significant differences in cellular drug resistance towards Acla could be demonstrated among FAB subtypes. Furthermore, in two cohorts of AML patients treated by two different regimens for remission induction over a period of 15 yr (1985-94, n = 159 and 1995-99, n = 76, respectively) we demonstrate in univariate analyses a significance of CD14 expression with respect to clinical outcome. With the exception of significance to probability of obtaining complete remission in the first cohort (P = 0.03, logistic regression), this significance was, however, lost in multivariate analyses. It was demonstrated that FAB-M4 patients were older than M5 patients and that high CD14 expression was associated with the presence of secondary AML and older age. We conclude that although cases with high blast cell CD14 expression (and FAB-M4 cases) were more resistant to Ara-C as well as Dau in vitro, the clinical and biological significance of this may be debatable because of interactions with major prognostic factors in AML.

Aclarubicin↗
PubMed2001

Clinical aspects of obesity in childhood and adolescence--diagnosis, treatment and prevention.

The level of fatness at which morbidity increases is determined on an acturial basis. Direct measurements of body fat content, eg hydrodensitometry, bioimpedance or DEXA, are useful tools in scientific studies. However, body mass index (BMI) is easy to calculate and is frequently used to define obesity clinically. An increased risk of death from cardiovascular disease in adults has been found in subjects whose BMI had been greater than the 75th percentile as adolescents. Childhood obesity seems to increase the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge on the role of neuropeptides such as POMC, neuropeptide Y (NPY) and the melanocyte concentrating hormone receptors (MC4R). Environmental/exogenous factors contribute to the development of a high degree of body fatness early in life. Twin studies suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders including a number of endocrine disorders (Cushing's syndrome, hypothyroidism, etc) and genetic syndromes (Prader-Labhard-Willi syndrome, Bardet-Biedl syndrome etc) that can present with obesity. A simple diagnostic algorithm allows for the differentiation between primary or secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia and psychosocial problems. Therapeutic strategies include psychological and family therapy, lifestyle/behavior modification and nutrition education. The role of regular exercise and exercise programs is emphasized. Surgical procedures and drugs used as treatments for adult obesity are still not recommended for children and adolescents with obesity. As obesity is the most common chronic disorder in the industrialized societies, its impact on individual lives as well as on health economics has to be recognized more widely. This review is aimed towards defining the clinical problem of childhood obesity on the basis of current knowledge and towards outlining future research areas in the field of energy homoeostasis and food intake control.

Adolescent↗
PubMed2001

Metabolites of Monascus ruber in silages.

A total of 233 silages were examined and found that Monascus ruber was present in 43 samples with counts between 1 x 10(3) and 9 x 10(6) colony-forming units (CFU)/g (mean: 2 x 10(5) CFU/g). Monacolin K(L) and the hydroxy acid monacolin K(A) were detected by liquid chromatography-mass spectrometry in 45 and 50 of 233 samples at levels ranging from 25-15 600 and 28-65 400 microg/kg, respectively. Citrinin was found with high-performance liquid chromatography-fluorescence detection (FLD) in 14 (6%) samples, the concentrations varied between 2.4 and 64.2 microg/kg. The concentrations of citrinin were low and toxic effects are not anticipated. Monacolin K(A) and monacolin K(L) occur frequently and in considerable amounts in silages. These metabolites are believed to influence the metabolic activity of rumen anaerobic fungi resulting in a poorer digestion of crude fibre.

Animals↗
PubMed2001

Treatment of hepatitis C infection in injection drug users.

Chronic hepatitis C is the most common infectious disease among injection drug users (IDUs). Because of the allegedly poor compliance of IDUs with treatment requirements and conditions, hepatologists recommend treatment only if former IDUs have spent 6 to 12 months drug free. The aim of this prospective study was to investigate whether opiate-dependent IDUs with chronic hepatitis C virus (HCV) infection can be treated successfully with interferon. Eligibility for the study meant IDUs had to be HCV-RNA positive by polymerase chain reaction. Subsequently 50 inpatients were enrolled during detoxification treatment. HCV treatment was started with interferon alfa-2a (through 1998) or a combined regimen consisting of interferon alfa-2a and ribavirin (begun in 1998). All patients were treated and supervised by specialized physicians in both hepatology and addiction medicine. The end point for this study was defined as a loss of detectable serum HCV RNA at week 24 after treatment. The rate of sustained virologic response was 36%. Sustained response rates were not significantly different for patients who relapsed and returned to treatment (53%), relapsed and did not return to treatment (24%), or did not relapse (40%; P >.05). During the 24 weeks after treatment, we were unable to detect any reinfection, even among patients who injected heroin during this period. This surprising result should be examined in further studies. In conclusion, HCV-infected drug addicts with chronic HCV infection can be treated successfully with interferon alfa-2a and ribavirin if they are closely supervised by physicians specialized in both hepatology and addiction medicine.

Adult↗
PubMed2001

Exercise training in heart failure: recommendations based on current research.

A review of methods used for exercise training in stable chronic heart failure patients (CHF) shows a lack of standardization to guide prescription. Previous recommendations have been adopted from fitness training or rehabilitation studies. A model for use in CHF patients requires specific guidelines which respect the various manifestations of this illness. Pathology and exercise tolerance of patients with CHF allow only a few selected activities to be performed, such as walking and cycle ergometer training. Although the steady state method has usually been applied for aerobic exercise, the interval method has been shown to cause greater exercise stimuli to peripheral muscle than that obtained during steady state training methods without inducing greater cardiovascular stress. There is no consensus at present as to an optimal parameter for measuring intensity. An intensity of 40-80% peak oxygen consumption (VO(2)) has been applied successfully. A heart rate reserve of 60-80% or 75% of peak heart rate was used as a guide to exercise intensity without consideration of the impaired force-frequency relationship in myocardial performance. Because intensity, duration, and frequency of exercise are closely interrelated, initial exercise should be kept at 40-50% peak VO(2) with exercise duration of > 3-5 min x session performed several times daily. Progression should be followed in this order: duration, then frequency, then intensity. Resistance training can be recommended when small muscle groups are involved, using short bouts of work phases and small numbers of repetitions. To increase respiratory muscle strength and endurance, resistive inspiratory muscle training at intensity 25--35% maximum inspiratory pressure, and performed 20-30 min x d(-1), is recommended. On the basis of currently available research, supervised inpatient training programs should be preferred. Future research should be performed with respect on statistically sufficient, randomized, and controlled long-term studies that compare different training modes, intensities, frequency/duration ratios, and rates of progression.

Exercise Therapy↗
PubMed2001

Successful incorporation of the Severe Head Injury Guidelines into a phased-outcome clinical pathway.

Clinical pathways have been proven to be valuable tools in improving outcomes in patients with neurological diagnoses. However, their use with trauma populations has been limited. The unpredictable nature of trauma makes it difficult to develop a day-by-day plan of care that would be applicable to all patients with the same trauma diagnosis. Nevertheless, a severe traumatic brain injury (TBI) clinical pathway was developed and implemented at a Level 1 Trauma Center with significant reductions in length of stay and number of ventilator days. With the publication of the Guidelines for the Management of Severe Head Injury, this pathway was refashioned into a severe TBI phased-outcome pathway. Rather than a day-by-day plan of care, this clinical pathway consists of four phases of care: (a) admission to the intensive care unit, (b) acute critical care, (c) mobility and weaning, and (d) pre-rehabilitation. After 12 months, the improvements accomplished by the original pathway have been maintained or exceeded.

Adult↗
PubMed2001

Melastomeae come full circle: biogeographic reconstruction and molecular clock dating.

Rhexia, with 11 species in the Coastal Plain province of North America, is the only temperate zone endemic of the tropical eudicot family Melastomataceae. It is a member of the only pantropical tribe of that family, Melastomeae. Based on the chloroplast gene ndhF, we use a fossil-calibrated molecular clock to address the question of the geographic origin and age of Rhexia. Sequences from 37 species in 21 genera representing the tribe's geographical range were analyzed together with five outgroups. To obtain better clade support, another chloroplast region, the rpl16 intron, was added for 24 of the species. Parsimony analysis of the combined data and maximum-likelihood analysis of ndhF alone indicate that the deepest split is between Rhexia plus its sister group, a small Central American genus, and all other Melastomeae. Old World Melastomeae are monophyletic and nested within New World Melastomeae. Although likelihood-ratio tests of clock and nonclock substitution models for the full or moderately pruned datasets rejected the clock, these models yielded identical topologies (for 30 taxa) with few significantly different branch lengths as assessed by a Student's t-test. Age estimates obtained were 22 million years ago (Mya) for the divergence of Rhexia from its sister group, 12 Mya for the dispersal of Melastomeae from the New World to West Africa, and 1 Mya for the diversification of Melastoma in Southeast Asia. The only other genus of Melastomeae to have reached Southeast Asia from Africa or Madagascar is Osbeckia. The age and geographic distribution of fossils, which come from Miocene sites throughout Eurasia, suggest that Melastomeae once ranged from Eurasia across Beringia to North America from whence they reached South America and subsequently Africa and Southeast Asia. Climate deterioration led to their extinction in the Northern Hemisphere, with Rhexia possibly surviving in Coastal Plain refugia.

Calibration↗
PubMed2001

Transcranial sonography of brain tumors in the adult: an in vitro and in vivo study.

BACKGROUND: Few reports indicate the potential of transcranial sonography (TCS) in detecting human brain tumors. METHODS: With an Agilent Sonos 2500 ultrasound device, the authors studied 4 brain tumor phantoms and compared the findings with magnetic resonance imaging (MRI). TCS was performed on 40 patients with intracranial tumors in a follow-up design. Sonographic tumor volume and affection of the ventricular system were compared with MRI findings. RESULTS: The authors found a good correlation between TCS and MRI volumetry in the in vitro study. TCS showed good intraobserver and interobserver reliability. A new volumetric formula for TCS measurement was determined. TCS detection rate of brain tumors in vivo was 40%. When the investigators were given access to radiological findings, the rate of tumor identification was 80%. Despite a sufficient acoustic window, 40% of gliomas grade II and III were not detected. One glioblastoma was not identified owing to an insufficient temporal acoustic window. Tumor volumes measured with MRI and TCS correlated well. MRI volumes exceeded TCS volumes by 41%. In the postoperative examinations (mean = 8 days postoperative, n = 15), the resection cavity was displayed as hyperechogenic. It appeared impossible to differentiate between residual tumor tissue and normal repair mechanisms or blood. In the follow-up examination (mean = 99 days postoperative, n = 15) in 5 patients, neither MRI nor TCS showed tumor regrowth. Ten patients had residual tumors that were detected by sonography. CONCLUSIONS: The value of TCS for the diagnostics of brain tumors is at present limited. Once the tumor has been identified, sonographic results match well with those of MRI.

Adolescent↗
PubMed2001

Selective recall of gastrointestinal-sensation words: evidence for a cognitive-behavioral contribution to irritable bowel syndrome.

OBJECTIVE: Selective attention to GI sensations has been suggested as an important mechanism that affects symptom perception in patients with irritable bowel syndrome (IBS), but this hypothesis has not yet been tested empirically. Differential recall of words describing negative affect has been used to demonstrate that depressed patients selectively attend to negative affect words. This technique may be useful for examining selective attention to somatic sensations. The aim of this study was to determine whether patients with IBS demonstrate selective recall of GI sensations compared with neutral words and words describing respiratory sensations. METHODS: A total of 16 IBS patients, nine asthmatic patients (medical controls), and eight healthy controls were shown 10 GI sensation words or phrases, 10 respiratory sensation words or phrases, and 10 neutral words in random order for 3 s each. After a distraction task, subjects wrote down all of the words or phrases they could remember. RESULTS: As predicted, IBS patients were more likely to recall GI words than other categories. Asthmatic patients were more likely to recall respiratory words in comparison with healthy controls. CONCLUSIONS: IBS patients selectively recall words describing GI sensations; this suggests that they may selectively attend to GI sensations, thus supporting the cognitive-behavioral theory of IBS.

Behavior↗
PubMed2001

Myocardial Infarction associated with methadone and/or dihydrocodeine.

Chest pain and myocardial infarction occurring in young people with angiographically normal coronary arteries is well documented. Opiates have a cardioprotective effect and are used in acute heart attacks. We described a 22-year-old opioid addicted male patient who suffered a myocardial infarction following the consumption of methadone and dihydrocodeine.

Adult↗
PubMed2001

Treatment with tissue plasminogen activator and inpatient mortality rates for patients with ischemic stroke treated in community hospitals.

BACKGROUND AND PURPOSE: Most analyses of intravenous tissue plasminogen activator (IV tPA) use for acute stroke in routine practice have been limited by sample size and generally restricted to patients treated in large academic medical facilities. In the present study, we sought to estimate among community hospitals the use of IV tPA and to identify factors associated with the use of IV tPA and inpatient mortality. METHODS: We evaluated a retrospective cohort of 23 058 patients with ischemic stroke from 137 community hospitals. RESULTS: Three hundred sixty-two (1.6%) patients were treated with IV tPA, and 9.9% of those patients died during the hospitalization period. In 35.0% of the hospitals, no patients were treated with IV tPA, whereas 14.6% of hospitals treated approximately 3.0% with IV tPA. After control for multiple factors, younger patients, more severely ill patients (OR 2.02, 95% CI 1.36 to 3.01), and patients treated in rural hospitals (OR 1.80, 95% CI 0.99 to 3.26) were more likely to receive IV tPA, whereas black patients were less likely (OR 0.54, 95% CI 0.31 to 0.95). There also was a trend showing that women were less likely to receive IV tPA (OR 0.84, 95% CI 0.69 to 1.03). Factors associated with an increased odds of inpatient mortality included receipt of IV tPA among men (OR 2.81, 95% CI 1.72 to 4.58) and increased age. Black patients were 27% less likely to die during hospitalization (95% CI 0.60 to 0.90). CONCLUSIONS: In this large, retrospective evaluation of community hospital practice, the use IV tPA and inpatient mortality rates among IV tPA-treated patients were consistent with those of other studies. The likelihood of receiving IV tPA varies by race, age, disease severity, and possibly gender. These factors may influence mortality rates.

Aged↗
PubMed2001

Mutational spectrum of the steroid 21-hydroxylase gene in Austria: identification of a novel missense mutation.

This study attempted an analysis of the mutational spectrum of 21-hydroxylase deficiency in 79 unrelated Austrian patients with classical and nonclassical forms of congenital adrenal hyperplasia and their respective 112 family members. Apparent large gene deletions/conversions were present in 31% of the 158 unrelated congenital adrenal hyperplasia alleles, whereas the most frequent point mutations were intron 2 splice (22.8%), I172N (15.8%), V281L (12%), and P30L (7.6%), in line with the frequencies reported for other countries. In 5 of the 12 congenital adrenal hyperplasia alleles carrying a P30L mutation the aberration is based on a single base substitution, whereas the remaining 7 represent part of a CYP21B conversion (1 allele) or CYP21B/21A hybrid gene (6 alleles), the latter characterized by a junction site before intron 2 as indicated by Southern blot, PCR, and sequence analyses. Previously described mutations were not present in 1.2% of unrelated congenital adrenal hyperplasia alleles, including one female patient presenting with severe genital virilization. Sequence analysis of the complete functional 21-hydroxylase gene revealed an as yet undescribed mutation in exon 10-Arg(426)His, which has not yet been described to represent a common pseudogene sequence. In vitro expression experiments showed the Arg(426)His mutant to exhibit only low enzyme activity toward the natural substrate 17-hydroxyprogesterone corresponding to the degree of disease manifestation in the patient in whom it was found.

Adrenal Hyperplasia, Congenital↗
PubMed2001

The fate of trenbolone acetate and melengestrol acetate after application as growth promoters in cattle: environmental studies.

The steroids trenbolone acetate (TbA) and melengestrol acetate (MGA) are licensed as growth promoters for farm animals in several meat-exporting countries. Although many studies have explored their safety for both animals and consumers, little is known about their fate after excretion by the animal. Our study aimed to determine the residues and degradation of trenbolone and MGA in solid dung, liquid manure, and soil. In animal experiments lasting 8 weeks, cattle were treated with TbA and MGA. Solid dung and, in case of trenbolone, liquid manure were collected and spread on maize fields after 4.5 and 5.5 months of storage, respectively. Determination of the hormone residues in all samples included extraction, clean-up (solid-phase extraction), separation of metabolites and interfering substances by HPLC (RP-18), and quantification by sensitive enzyme immunoassay. Procedures were validated by mass spectrometry (MS) methods. During storage of liquid manure the level of trenbolone decreased from 1,700 to 1,100 pg/g (17alpha-isomer), corresponding to a half-life of 267 days. Before storage, the concentrations in the dung hill ranged from 5 to 75 ng/g TbOH and from 0.3 to 8 ng/g MGA. After storage, levels up to 10 ng/g trenbolone, and 6 ng/g MGA were detected. In the soil samples trenbolone was traceable up to 8 weeks after fertilization, and MGA was detected even until the end of the cultivation period. The results show that these substances should be investigated further concerning their potential endocrine-disrupting activity in agricultural ecosystems.

Agriculture↗
PubMed2001

Estimates of covariance functions for growth from birth to 630 days of age in Nelore cattle.

Weight records of Brazilian Nelore cattle, from birth to 630 d of age, recorded every 3 mo, were analyzed using random regression models. Independent variables were Legendre polynomials of age at recording. The model of analysis included contemporary groups as fixed effects and age of dam as a linear and quadratic covariable. Mean trends were modeled through a cubic regression on orthogonal polynomials of age. Up to four sets of random regression coefficients were fitted for animals' direct and maternal, additive genetic, and permanent environmental effects. Changes in measurement error variances with age were modeled through a variance function. Orders of polynomial fit from three to six were considered, resulting in up to 77 parameters to be estimated. Models fitting random regressions modeled the pattern of variances in the data adequately, with estimates similar to those from corresponding univariate analysis. Direct heritability estimates decreased after birth and tended to be lowest at ages at which maternal effect estimates tended to be highest. Maternal heritability estimates increased after birth to a peak around 110 to 120 d of age and decreased thereafter. Additive genetic direct correlation estimates between weights at standard ages (birth, weaning, yearling, and final weight) were moderate to high and maternal genetic and environmental correlations were consistently high.

Age Factors↗
PubMed2001

Identification of novel peroxisome proliferator-activated receptor alpha (PPARalpha) target genes in mouse liver using cDNA microarray analysis.

Peroxisome proliferators, which function as peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists, are a group of structurally diverse nongenotoxic hepatocarcinogens including the fibrate class of hypolipidemic drugs that induce peroxisome proliferation in liver parenchymal cells. Sustained activation of PPARalpha by these agents leads to the development of liver tumors in rats and mice. To understand the molecular mechanisms responsible for the pleiotropic effects of these agents, we have utilized the cDNA microarray to generate a molecular portrait of gene expression in the liver of mice treated for 2 weeks with Wy-14,643, a potent peroxisome proliferator. PPARalpha activation resulted in the stimulation of expression (fourfold or greater) of 36 genes and decreased the expression (fourfold or more decrease) of 671 genes. Enhanced expression of several genes involved in lipid and glucose metabolism and many other genes associated with peroxisome biogenesis, cell surface function, transcription, cell cycle, and apoptosis has been observed. These include: CYP2B9, CYP2B10, monoglyceride lipase, pyruvate dehydrogenase-kinase-4, cell death-inducing DNA-fragmentation factor-alpha, peroxisomal biogenesis factor 11beta, as well as several cell recognition surface proteins including annexin A2, CD24, CD39, lymphocyte antigen 6, and retinoic acid early transcript-gamma, among others. Northern blotting of total RNA extracted from the livers of PPARalpha-/- mice and from mice lacking both PPARalpha and peroxisomal fatty acyl-CoA oxidase (AOX), that were fed control and Wy-14,643-containing diets for 2 weeks, as well as time course of induction following a single dose of Wy-14,643, revealed that upregulation of genes identified by microarray procedure is dependent upon peroxisome proliferation vis-à-vis PPARalpha. However, cell death-inducing DNA-fragmentation factor-alpha mRNA, which is increased in the livers of wild-type mice treated with peroxisome proliferators, was not enhanced in AOX-/- mice with spontaneous peroxisome proliferation. These observations indicate that the activation of PPARalpha leads to increased and decreased expression of many genes not associated with peroxisomes, and that delayed onset of enhanced expression of some genes may be the result of metabolic events occurring secondary to PPARalpha activation and alterations in lipid metabolism.

Animals↗
PubMed2001

The DSL analog free testosterone assay: serum levels are not related to sex hormone-binding globulin in normative data throughout childhood and adolescence.

In this study we tested the performance of easy-to-use and rapid, commercially available immunoassays to measure free testosterone (fT) and sex hormone-binding globulin (SHBG). We asked whether fT and SHBG serum levels are age-dependent and whether or not there is a gender dependence of fT and SHBG in this age group. Finally, by measuring fT and SHBG in sera of a cohort of healthy children and adolescents using commercially available immunoassays, we established normative data for fT and SHBG in this age group: in boys fT levels increased significantly (r=0.83, p<0.0001) from 0.63 pmol/l (median) in the age group below 5 years to 56.9 pmol/l in the age group 16-20 years. In girls fT levels also increased with age (r=0.66, p<0.0001): from 0.72 pmol/l (median) in the age group below 5 years to 3.34 pmol/l in the age group 16-20 years. In contrast, SHBG serum concentrations significantly decreased with age in boys (r=-0.62, p<0.0001) but remained constant in girls (r=0.04, n.s.). Importantly, fT values were independent of SHBG levels as determined by our methods. In conclusion, fT can be measured in an acceptable quality using the DSL analog tracer-based immunoassay and normative data are now available. In addition, SHBG levels in healthy children and adolescents are also given and may permit for studies of pathophysiologic states in this age group.

Adolescent↗