Biomedical subjects

J Beyer

Publications and source records attributed to J Beyer.

At least 19 recordsLinked to original sources

PubMed1999

Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial.

We performed a prospective, randomized, multicenter trial to evaluate the effectiveness of prophylactic inhalations with aerosolized amphotericin B (aeroAmB) to reduce the incidence of invasive aspergillus (IA) infections in patients after chemotherapy or autologous bone marrow transplantation and an expected duration of neutropenia of at least 10 days. From March 1993 until April 1996, 382 patients with leukemias, relapsed high-grade non-Hodgkin lymphomas, or solid tumors were randomized with a 13:10 ratio to receive either prophylactic aeroAmB inhalations at a dose of 10 mg twice daily or no inhalation prophylaxis in an unblinded fashion. The incidence of proven, probable, or possible IA infections was 10 of 227 (4%) in patients who received prophylactic aeroAmB. This did not differ significantly from the 11 of 155 (7%) incidence in patients who received no inhalation prophylaxis (P =.37). Moreover, no differences in the overall mortality (13% v 10%; P =.37) or in the infection-related mortality (8% v 7%; P =.79) were found. In contrast to other nonrandomized trials, we observed no benefit from prophylactic aeroAmB inhalations, but the overall incidence of IA infections was low.

Administration, Inhalation↗

PubMed1999

The effect of human proinsulin C-peptide on erythrocyte deformability in patients with Type I diabetes mellitus.

AIMS/HYPOTHESIS: In recent years, evidence has arisen that proinsulin C-peptide exerts biological effects especially on microcirculation, e.g. C-peptide has been shown to increase skin microcirculation in patients with Type I (insulin-dependent) diabetes mellitus and to activate endothelial nitric oxide synthase. This study aimed to investigate the influence of pro-insulin C-peptide on erythrocyte deformability which was assessed by means of laser diffractoscopy. METHODS: Blood samples from healthy control subjects (n = 10) and Type I diabetic patients (n = 15) completely deficient of C-peptide were analysed at shear stresses ranging from 0.3 to 30 Pa. RESULTS: Erythrocyte deformability was lower in the group of Type I diabetic patients than in the control subjects. Preincubation of the diabetic blood samples with various concentrations of human proinsulin C-peptide for 8 h restored the deformability of erythrocytes, almost reaching the values of control samples. In contrast, proinsulin C-peptide did not modify the erythrocyte deformability of control subjects. CONCLUSION/INTERPRETATION: We conclude that proinsulin C-peptide is able to ameliorate the impaired deformability of erythrocytes in Type I diabetic patients and we hypothesise that this effect is mediated by restoration of Na(+)-K(+)-ATPase activity, which is known to be attenuated in diabetic patients.

C-Peptide↗

PubMed1999

Confocal laser scanning microscopy: A nondestructive subsurface histotomography of healthy human bone.

Microscopy of bony tissue usually requires special treatment for decalcification and processing of thin sections. Confocal laser scanning microscopy (CLSM) allows the nondestructive histotomography of organic hard tissue. The aim of this study was to visualize healthy human bone structures and to correlate identical areas in CLSM and conventional light microscopy. Each sample of healthy human lower jaw (n = 20) was divided into three parts: (1) fresh, untreated bony blocks studied by CLSM; (2) MMA-embedded thin sections (without decalcification), HE stained and studied by CLSM and conventional light microscopy (correlation of identical areas); (3) decalcificated, HE stained, histological sections studied by conventional light microscopy. In untreated bony blocks, microstructures such as osteocytes and lamellae were identified by CLSM. These structures could be correlated with conventional light microscopy. In CLSM, subcellular structures cannot yet be interpreted, whereas cytoplastic processes of osteocytes were seen with high contrast. With CLSM, nondestructive histology of cortical bone can be obtained. The risk of artifacts due to pretreatment is minimized, and subsurface visualization does not affect the interpretation.

Histological Techniques↗

PubMed1999

Serum leptin is associated with serum uric acid concentrations in humans.

This cross-sectional study aimed to evaluate the relationship between leptin and the cluster of abnormalities often referred to as the metabolic syndrome. The serum leptin concentration, body mass index (BMI), percent body fat, total fat mass (FM), waist and hip circumference, waist to hip ratio (WHR), prevalence of hypertension, and triglyceride (TG), lipoprotein, and uric acid concentration were determined in 86 type 2 diabetic (n = 59) and healthy (n = 27) subjects. Multiple regression analyses showed that the estimates of total body obesity (BMI, percent body fat, and total FM), sex, and serum uric acid concentration are independently associated with the serum leptin concentration. The finding of a positive correlation between serum leptin and uric acid levels suggests that leptin could be a pathogenic factor responsible for hyperuricemia in obesity.

Adipose Tissue↗

PubMed1999

The burden of dementia. A medical and research perspective.

Alzheimer's disease remains the most common form of dementia. Dementia symptoms vary depending on individual personality, life experience, and social and cultural influences. As dementia progresses, involvement of multi-disciplinary health care professionals is needed to manage the disease. Alzheimer research is progressing rapidly. While 5% of all Alzheimer's disease may be genetically determined, the majority is not. Susceptibility genes can reveal the risk of contracting Alzheimer's disease. Early life risk factors such as education, nutrition, and vascular disease may increase the likelihood of dementia in later life. In the United States, two acetylcholinesterase inhibitors have been approved as cognitive enhancers. Possible prevention and symptomatic treatment interventions have focused on estrogen replacement therapy, antioxidants, and anti-inflammatory medications. Research advances have improved the clinical management of dementia. Ethical implications to the patient, family, and society are multiple and remain challenging.

Aged↗

PubMed1999

Binding of monocytes from normolipidemic hyperglycemic patients with type 1 diabetes to endothelial cells is increased in vitro.

Increased endothelial binding and emigration of monocytes play a dominant role in the pathogenesis of atherosclerosis in diabetes mellitus. Previous studies revealed that hyperlipidemia correlates with monocyte binding in vitro. The aim of this study was to characterize the monocyte-endothelial interaction of leucocytes of hyperglycemic patients with type 1 diabetes but lacking hyperlipidemia. We isolated monocytes from healthy controls and normolipidemic type 1 diabetes patients with elevated levels of HbA1c and quantified monocyte binding by an immunoilluminometric cell adhesion assay. Purity of isolated monocytes was at least 98%. Endothelial binding of monocytes from patients with type 1 diabetes was found to be significantly increased compared to controls (19.2 +/- 3.9% vs. 14.9 +/- 3.5%). This difference of monocyte binding remained unchanged if the endothelial cells were stimulated with 27.7 mmol/l glucose for seven days prior to adhesion studies (31.5 +/- 4.9% in diabetes patients vs. 25.8 +/- 4.1% in controls) whereby monocyte binding markedly increased under these hyperglycemic conditions. Furthermore, an increased CD11b expression could be demonstrated on monocytes of normolipidemic hyperglycemic type 1 diabetes patients. Thus, we suggest that hyperglycemia per se may contribute to increased monocyte binding to endothelial cells by promoting leucocyte integrin expression. Recently performed studies of our group strengthen the hypothesis that this monocyte activation is mediated by stimulation of the beta-isoform of proteinkinase C.

Adult↗

PubMed1999

Gemcitabine in patients with relapsed or cisplatin-refractory testicular cancer.

PURPOSE: Despite generally high cure rates in patients with metastatic testicular germ cell tumors, patients with incomplete response to cisplatin-based first-line therapy or with relapsed disease after high-dose salvage chemotherapy have a very poor prognosis. This phase II study evaluates the use of gemcitabine in patients with intensively pretreated or cisplatin-refractory testicular germ cell cancers. PATIENTS AND METHODS: Thirty-five patients (median age, 33 years) were enrolled; 31 patients were fully assessable. All patients had metastatic nonseminomatous germ cell tumors; eight patients had extragonadal primary tumors. Twenty patients (63%) had lung metastases, and 12 patients (39%) had liver metastases. The median number of prior cisplatin-based chemotherapy cycles was seven; 22 patients (71%) had received high-dose chemotherapy with autologous stem-cell transplantation, and 19 patients (61%) had received treatment with paclitaxel. Seventeen patients (54%) were considered refractory or absolutely refractory to chemotherapy. RESULTS: Six of 31 assessable patients (19%) responded favorably to gemcitabine, 11 patients (35%) displayed no change, and 14 patients (45%) had disease progression. The median time to treatment failure was 4 months (range, 2 to 9+ months), and the median survival was 6 months (range, 2 to 23 months). Patients received a median of six gemcitabine applications. Ten patients (32%) required dose reductions, mainly owing to hematologic toxicity. Grade 3/4 granulocytopenia occurred in four patients (13%) and grade 3/4 thrombocytopenia in seven patients (22%). One case of severe sepsis was observed. CONCLUSION: Gemcitabine displays antitumor activity in intensively pretreated and refractory germ cell tumors. Responses were observed in approximately 20% of patients, including three of 22 patients after previous high-dose chemotherapy and one of four patients with mediastinal tumors. Gemcitabine may be a reasonable palliative option for intensively pretreated patients and should be further investigated to define its role in the risk-adapted treatment strategies for germ cell tumors.

Adolescent↗

PubMed1999

Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products.

Advanced glycation end products (AGEs) have been identified as relevant mediators of late diabetic complications such as atherosclerotic disease. The endothelial migration of monocytes is one of the first steps in atherogenesis and monocyte-endothelial interaction itself is linked to the expression of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1). Recently, stimulation of VCAM-1 by AGEs has been demonstrated. Since endothelial stimulation by AGEs is followed by generation of oxygen free radicals with subsequent activation of nuclear transcription factor kappaB, we investigated the influence of alpha-lipoic acid on the expression of VCAM-1 and monocyte adherence to endothelial cells in vitro by means of cell-associated chemiluminescence assays and quantitative reverse transcriptase polymerase chain reaction using a constructed recombinant RNA standard. We found that alpha-lipoic acid was able to decrease the number of VCAM-1 transcripts from 41. 0+/-11.2 to 9.5+/-4.7 RNA copies per cell in AGE-stimulated cell cultures. Furthermore, expression of VCAM-1 was suppressed in a time- and dose-dependent manner by alpha-lipoic acid as shown by chemiluminescence endothelial cell assay. Pretreatment of endothelial cells with 0.5 mM or 5 mM alpha-lipoic acid reduced AGE-induced endothelial binding of monocytes from 22.5+/-2.9% to 18. 3+/-1.9% and 13.8+/-1.8% respectively. Thus, we suggest that extracellularly administered alpha-lipoic acid reduces AGE-albumin-induced endothelial expression of VCAM-1 and monocyte binding to endothelium in vitro. These in vitro results may contribute to the understanding of a potential antioxidative treatment of atherosclerosis.

Antioxidants↗

PubMed1999

Coupled-column liquid chromatographic analysis of catecholamines, serotonin, and metabolites in human urine.

A column-switching HPLC system was utilized for the simultaneous determination of epinephrine, norepinephrine, dopamine, serotonin, and their metabolites metanephrine, normetanephrine, 3, 4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid in human urine. The sample was injected directly onto a C18-alkyl-diol silica precolumn, which separated the analytes from matrix. The analytes were eluted from the precolumn onto the analytical column by the use of column-switching techniques and were then separated on the analytical column by means of ion-pair reversed-phase HPLC. The analytes were then oxidized to the corresponding quinones and converted into fluorescent derivatives by reaction with meso-1,2-diphenylethylenediamine.

Case-Control Studies↗

PubMed1998

[Bioequivalence of a combination of levothyroxine and iodine in comparison with levothyroxine only. A controlled double-blind study of bioavailability].

BACKGROUND: Iodine deficiency is the main cause of endemic goitre. Iodine supplementation and decrease of pituitary TSH are the therapeutical aims. In this study, bioavailability of levothyroxine combined with iodide and the same dose of levothyroxine alone were compared. PATIENTS AND METHODS: Fourty-eight subjects aged 18 to 40 years were randomly assigned for 6 days either 150 micrograms levothyroxine and 150 micrograms iodide (group A, n = 25) or 150 micrograms levothyroxine (group B, n = 23). Baseline TSH and thyroid hormones were measured 2 days before starting therapy as well as daily till day 6. TRH-test (delta TSH) and thyroid sonography were performed at day -2 and 6. RESULTS: During therapy baseline TSH decreased markedly from 1.26 to 0.35 mU/ml (median) in group A and from 1.37 to 0.39 to 0.39 mU/ml in group B (both p < 0.001), as well as delta TSH (A from 5.66 to 2.61 mU/ml; B from 6.3 to 2.95 mU/ml; p < 0.001). Difference of delta TSH (day -2 versus day 6) was negatively correlated to body surface (r = -0.307; p < 0.05). TT4 levels increased in both groups (A from 7.1 to 9.1 microU/dl; B from 7.2 to 9.4 microU/dl; p < 0.005). No significant differences were noted between both groups for thyroid-related parameters. In both groups, confidence intervals for baseline TSH and TT4 were in the expected range. CONCLUSION: In this study, similar bioavailability and bioequivalence for levothyroxine and the combination of levothyroxine with iodide were demonstrated.

Adolescent↗

PubMed1998

[Individually dosed levothyroxine with 150 micrograms iodide versus 100 micrograms levothyroxine combined with 100 micrograms iodide. A randomized double-blind trial].

BASIC PROBLEM AND OBJECTIVE: Intrathyroid deficiency and the influence of thyroid stimulating hormone (TSH) are the main pathogenetic factors in the development of endemic euthyroid goitre. Goitre reduction is achieved with either administration of levothyroxine, which diminishes hypophyseal TSG production, or of iodide. Aim of this study was to compare the efficacy of treatment with a dose-fixed combination of levothyroxine plus iodide with that of an individualized dosage of levothyroxine plus iodide. PATIENTS AND METHODS: After randomization 49 patients with euthyroid goitre (24 women, 25 men, aged 20-43 years) were treated for 12 weeks in a double-blind trial. Patients in group A received levothyroxine in a weight-adapted dosage (75,100 or 150 micrograms) plus 150 micrograms iodide, while those in group B were given a fixed dosage of 100 micrograms levothyroxine plus 100 micrograms iodide. Basal TSH, thyroid hormones, iodide excretion, hyperthyroid score and sonographic volume of the thyroid were determined before treatment and after 12 weeks. RESULTS: Basal TSH levels were reduced in both groups (P < 0.0001), without significant difference between the two groups (median relative change: group A 78.1%, group B 52.8%). Thyroid volume was decreased independently of the form of treatment (P < 0.0001) (median relative reduction: group A 37.6%, group B 30.9%; difference not significant). Iodide excretion rose in both groups, without significant difference (group A 107%, group B 49%). There was hardly any change of the hyperthyroid score in both groups. There were no side effects. CONCLUSION: Both forms of medication were equally efficacious and well tolerated in the treatment of euthyroid goitre.

Adult↗

PubMed1998

Biological activity of C-peptide on the skin microcirculation in patients with insulin-dependent diabetes mellitus.

19 insulin-dependent diabetes mellitus (IDDM) patients participated in a randomized double-blind crossover investigation to investigate the impact of human C-peptide on skin microvascular blood flow. The investigation was also carried out with 10 healthy volunteers. Blood pressure, heart rate, blood sugar, and C-peptide levels were monitored during a 60-min intravenous infusion period of C-peptide (8 pmol kg-1 min-1) or saline solution (154 mmol liter-1 NaCl), and 30 min after stopping the infusion. During the same time period, capillary blood cell velocity (CBV), laser Doppler flux (LDF), and skin temperature were assessed in the feet. In the verum arm, C-peptide levels increased after starting infusion to reach a maximum of 2.3+/-0.2 nmol liter-1 after 45 min, but remained below 0. 15 nmol liter-1 during the saline treatment. Baseline CBV was lower in diabetic patients compared with healthy subjects (147+/-3.6 vs. 162+/-4.2 micron s-1; P < 0.01). During C-peptide administration, CBV in IDDM patients increased progressively from 147+/-3.6 to 167+/-3.7 micron s-1; P < 0.001), whereas no significant change occurred during saline infusion or in healthy subjects. In contrast to the CBV measurements, the investigation of LDF, skin temperature, blood pressure, heart rate, or blood sugar did not demonstrate any significant change during the study. Replacement of human C-peptide in IDDM patients leads to a redistribution in skin microvascular blood flow levels comparable to levels in healthy subjects by increasing the nutritive CBV relative to subpapillary arteriovenous shunt flow.

Adult↗

PubMed1998

Eye movements in depth: What does the monkey's parietal cortex tell the superior colliculus?

We have recorded identified cortico-tectal neurons from the primate parietal cortex to determine whether the depth-related activity in the intraparietal sulcus (area LIP) is transmitted to the superior colliculus. Traditional theory suggests that the superior colliculus is involved in the control of conjugate, saccadic eye movements and thus would not require inputs related to depth. We provide conclusive evidence that area LIP neurons in fact do transmit depth-related information to the superior colliculus.

Animals↗

PubMed1998

High-dose chemotherapy with autologous stem cell support in poor-risk germ cell tumors.

High-dose chemotherapy (HDT) and stem cell transplantation is a newer treatment option widely applied in poor-risk germ cell tumor patients. Due to the increasing practical clinical experience and the availability of hematopoietic growth factors, this treatment approach has become a relatively safe procedure. Depending on the drugs used. the most prominent therapy-associated side effects are myelosuppression, infections, mucositis, moderate, mostly reversible neurotoxicity, and renal impairment. Because of their unique pharmacologic characteristics, carboplatin and etoposide have proved to be the most important drugs for HDT. It is not known whether the addition of ifosfamide or cyclophosphamide or other drugs to the combination of carboplatin and etoposide leads to superior results. It is not yet clear if HDT should already be instituted in first-line treatment of poor-risk patients, or later after relapse or incomplete response. Even if precise data on the therapeutic value of HDT are still missing because randomized trials are not yet ready for evaluation, there is good evidence for the effectiveness of HDT. The demonstration of remissions in cisplatin-refractory patients, the inversion of remission durations, and the induction of long-term freedom from disease in multiply relapsed patients who were deemed incurable with conventional-dose procedures argue in favor of HDT. Finally, the delineation of prognostic factors associated with a poor probability of survival after HDT contributes to the selection of patients who are likely to profit from HDT and those who should be spared from dose-intensive treatment.

Antineoplastic Agents↗

PubMed1998

Is there an ectopic secretion of monomeric calcitonin in the human being?

INTRODUCTION: Persistent detectable calcitonin (CT) values can be frequently observed after treatment of medullary thyroid carcinomas (MTCs). Apart from residual C cells or incomplete tumor extirpation, ectopic CT production should be taken into account. CT determination in patients without MTC and after total thyroidectomy should reveal to what extent, apart from the C cells, other neuroendocrine cells show a relevant CT production. OBJECTIVES: The objective of this study was to find out whether ectopic CT production can be detected using an assay specifically recognizing the monomeric form of CT. METHODS: The CT serum values were obtained from 94 healthy individuals and 64 patients who had undergone total thyroidectomy and radioiodine therapy because of follicular or papillary carcinoma. RESULTS: In the group of thyroidectomized patients, the CT values were below the detection limit of the assay. In the tested patients, there was neither a physiological (C cell) nor a pathological (MTC cell) secretion of monomeric CT. CONCLUSION: A relevant ectopic monomeric CT production could be excluded because the patients were without detectable CT concentration. For this reason, postoperative CT concentrations of the monomeric form in MTC patients can be traced either to remaining C cells or to tumor cells. For a differentiation of these two possibilities further diagnostics is necessary.

Adult↗

PubMed1998

High-dose chemotherapy in germ cell tumours: a large single centre experience.

High-dose chemotherapy (HDCT) has evolved as a strategy to improve the treatment outcome in patients with relapsed and/or refractory germ cell tumours. Between August 1989 and September 1995, 150 consecutive patients with relapsed and/or refractory germ cell tumours were treated with conventional-dose salvage chemotherapy followed by one cycle of HDCT with carboplatin 1500-2000 mg/m2, etoposide 1200-2400 mg/m2 and ifosfamide 0-10 g/m2 and were retrospectively analysed. With a median follow-up time of 55 months (range 21-88 months) 51/150 (34%) patients are alive and disease free. The projected event-free and overall survival are 29% (confidence interval 22-37%) and 39% (confidence interval 31-47%) respectively. The relevance of prognostic variables for long-term survival after HDCT were prospectively confirmed. Persisting toxicities occurred in approximately one third of the long-term survivors. Treatment intensification with HDCT resulted in a significant proportion of the long-term survivors in patients with relapsed and/or refractory germ cell tumours. Trials to prospectively evaluate HDCT as an early intervention in these patients seem justified.

Adolescent↗

PubMed1998

Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation.

Donor lymphocyte infusions (DLI) are an effective treatment of leukemia relapse after allogeneic bone marrow transplantation. Undesired side-effects are the development of graft-versus-host disease (GVHD) and the occurrence of pancytopenia in some patients. In a pilot study, we investigated if unmanipulated G-CSF-mobilized peripheral blood stem cells which naturally contain large numbers of T lymphocytes (D-PBSC/LI) would be equally effective or even superior than DLI in generating a graft-versus-leukemia reaction (GVL) but could mitigate or prevent the development of pancytopenia. We treated 12 patients with CML chronic phase (n = 5), CML blast crisis (n = 2), AML (n = 2), ALL (n = 1), CLL (n = 1) and multiple myeloma (n = 1). In five patients with acute leukemia or CML blast crisis D-PBSC/LI followed intensive chemotherapy (group A), in seven patients D-PBSC/LI were given without any prior chemotherapy (group B). In group A two patients were evaluable for hematologic toxicity. Leukopenia <1000/microl lasted for 10 and 19 days, and thrombocytopenia <20,000/microl for 11 and 13 days, respectively. In group B leukopenia <1000/microl and thrombocytopenia <20,000/microl was observed in only one patient. Moderate cytopenia developed in four of five evaluable patients. A complete remission could be achieved in all seven patients with CML who all developed acute and/or chronic GVHD. None of the remaining five patients achieved a complete remission despite acute and/or chronic GVHD in two of them. Four patients died from disease progression, one patient from a secondary lymphoma, and one patient as a result of uncontrolled GVHD. In conclusion, D-PBSC/LI is effective in inducing GVL reaction but it does not prevent pancytopenia in each case. It remains unclear if it mitigates the incidence and severity of pancytopenia.

Adult↗

PubMed1998

Detection of tumor cells in peripheral blood samples from patients with germ cell tumors using immunocytochemical and reverse transcriptase-polymerase chain reaction techniques.

The aim of this study was to establish sensitive techniques for the detection of residual germ cell tumor cells in peripheral blood and progenitor cell harvests. For this purpose, we used immunocytochemical staining for cytokeratin filaments and reverse transcriptase-polymerase chain reaction (RT-PCR) for epidermal growth factor receptor (EGF-R) and germ cell alkaline phosphatase (GCAP). Germ cell tumor lines Tera-1 and Tera-2 were titrated into normal peripheral blood. Immunocytochemical staining allowed detection of one cytokeratin-positive tumor cell in 10(5) cells. RT-PCR for EGF-R revealed one tumor cell in 10 cells for Tera-1 and one tumor cell in 10(3) cells for Tera-2, while RT-PCR for GCAP displayed a sensitivity of one tumor cell in 10(6) cells for Tera-1, one tumor cell in 10(4) cells for Tera-2, and no positivity in normal mononuclear cells (n = 20) and progenitor cell harvests (n = 5). The analysis of peripheral blood and progenitor cell harvests from 20 patients with germ cell tumors revealed tumor cell contamination in three patients using immunocytochemical staining and in seven patients by RT-PCR for GCAP. We conclude that RT-PCR for GCAP appears to be suitable for the sensitive detection of residual germ cell tumor cells in peripheral blood and progenitor cell harvests.

Alkaline Phosphatase↗