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Biomedical subjects

H Ludwig

Publications and source records attributed to H Ludwig.

At least 145 records · Page 8Linked to original sources
PubMed1995

Interferon-alpha for induction and maintenance in multiple myeloma: results of two multicenter randomized trials and summary of other studies.

BACKGROUND: Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding response rates, maintenance duration, and survival times. Further randomized trials and global evaluations of available data are urgently needed for clarification. PATIENTS AND METHODS: 256 patients participated in a randomized trial, 125 on IFN + VMCP, and 131 on VMCP alone. 100 patients were randomized to IFN maintenance (n = 46) or were untreated controls (n = 54). Global evaluations are based on 1,518 patients in induction and 924 in maintenance trials. RESULTS: The induction trial demonstrated a significantly (p < 0.05) lower rate of progressive disease under IFN + VMCP (10.6%) than under VMCP (22.9%), but this benefit was limited to stage I or II patients. Median progression-free survival was longer in the IFN + VMCP arm (23.2 months vs. 15.8 months); median overall survival did not differ significantly (38.9 vs. 30.2 months). The IFN maintenance treatment trial showed significantly superior results in the IFN arm versus controls (median maintenance duration: 17.8 months and 8.2 months (p < 0.01), survival: 50.6 and 34.4 months (p < 0.05), respectively). Previous IFN treatment increased the benefits of IFN maintenance therapy. Adverse effects of IFN during induction were hematologic toxicity, fever, and infections, requiring dose reductions. Toxic effects of IFN maintenance treatment were mild. Global evaluations of randomized trials showed small but significant benefits of combined IFN induction therapy and significantly prolonged maintenance duration and survival under IFN maintenance. CONCLUSIONS: Presently available data support the use of IFN maintenance treatment because it significantly prolongs maintenance duration and survival. IFN added to induction chemotherapy resulted in minor improvements at the expense of increased toxicity, highlighting the need for better induction regimens.

Adult↗
PubMed1995

Staggering disease in cats: isolation and characterization of the feline Borna disease virus.

A Borna disease virus (BDV)-like agent was isolated from the central nervous system (CNS) of cats with a spontaneous non-suppurative encephalomyelitis ('staggering disease'). In contrast to the rabbit-adapted BDV strain V, which can be propagated in several primary and permanent cell cultures, the cat virus grew only in embryonic mink brain cells. Infection of adult Wistar rats with feline brain tissue material did not result in clinical disease during a period of 5 months, nor in growth of infectious virus in the brain. However, using the brain suspension of a newborn rat inoculated with feline brain tissue material, it was possible to induce typical Borna disease (BD) in four adult rats. This indicates a possible adaptation of the cat virus during passages in rats. By the use of an RT-PCR technique, BDV-specific RNA could be detected in a majority of brain samples from diseased cats. BDV-specific antigen was demonstrated in feline CNS samples both by immunohistochemistry and ELISA. However, the amount of BDV RNA and BDV antigen was less in the cats as compared to horses with BD, providing further support for the notion that a distinct feline BDV strain exists.

Animals↗
PubMed1995

The diagnostic value of urinary pyridinium cross-links of collagen, serum total alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease.

Bone metastases strongly affect skeletal metabolism by both their growth and their paracrine activities. However, so far no specific laboratory marker has been found to signal the spread of neoplastic disease to bone. We performed a cross-sectional study of 153 cancer patients and an equal number of healthy controls matched for sex and age, in which we determined serum levels of calcium and total alkaline phosphatase (TAP) as well as the fasting urinary excretion of calcium (uCa) and of the collagen cross-links pyridinoline (uPYD) and deoxypyridinoline (uDPD). The aim of the study was to analyze the diagnostic validity of the biochemical parameters measured with regard to neoplastic bone involvement. In the cancer group, 98 patients had overt bone metastases, as judged from radiographic and radioisotopic bone imaging. The remaining 55 patients were also in an advanced stage of disease, but there was no evidence of malignant bone involvement. In comparison to healthy controls, patients both with and without metastatic bone disease had significantly higher levels of TAP, uPYD, and uDPD (P < 0.0001). Only in cancer patients with bone metastases was the median serum calcium level higher than in the healthy controls (P < 0.02). uCa was the same in cancer patients and the control group. Within the collective of cancer patients, individuals with skeletal metastases had higher levels of serum calcium (P < 0.05), TAP (P < 0.01), and uPYD and uDPD (both P < 0.0001), than patients without evidence of malignant bone disease. uCa did not differ between the 2 groups of cancer patients. The cancer patients were then stratified into 4 subgroups according to the serum calcium level (< or = 2.6 mmol/L >) and the absence or evidence of bone metastases. This stratification revealed that in patients with bone metastases, uPYD and uDPD levels were similar in normocalcemic and hypercalcemic subjects, whereas in hypercalcemic patients, uCa levels significantly exceeded those in normocalcemic patients. When the efficacy of TAP, uCa, uPYD, and uDPD in discriminating between patients with and without bone metastases was evaluated by use of receiver-operating characteristic curves and stepwise multivariate regression analysis, uPYD was found to have the highest diagnostic validity. Using 50 mumol PYD/mol creatinine (i.e. the upper limit of normal range) as the cut-off level, the sensitivity of uPYD was 88.7%, whereas the specificity was only 41.8% (odds ratio, 5.598; 95% confidence interval, 2.547-12.306).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Borna disease--neuropathology and pathogenesis.

Natural BD is a nonpurulent acute/subacute encephalitis of horses and sheep with a propensity to involve the olfactory and limbic systems, and the brain stem. The inflammation is concentrated primarily in the gray matter, but subcortical white matter may also be affected. Experimental BD can be produced in a series of animals from birds to primates. The neuropathology after experimental infection is similar to that in natural disease but the inflammatory changes are more diffuse. In the rat and mouse, a persistent/tolerant infection can also be induced, in which inflammatory changes are conspicuously absent. In the course of persistent infection of the rat, an elective, focal degeneration ensues that involves the dentate gyrus, retina, and, less frequently, the magnocellular part of the hippocampus. The cytopathic destruction of the dentate gyrus is the likely anatomical substrate of learning deficiencies and behavioral changes, prominent features of chronic infection. Later in infection, more diffuse and random degeneration of neurons can be found. In all species infected, viral antigens are produced in excess and fill all neuronal processes. Beside neurons, glial cells are infected as well. The agent spreads in the nervous system axonally and transsynaptically (transneuronally). The type of neurotransmitter receptors in the synapse and their interaction with viral proteins may modulate the spread of infection (Gosztonyi et al. 1994). Virus particles have not been visualized in the brain in any phase of the disease. During persistent infection of the rat, production of viral proteins has a phasic character. Some rats survive acute infection and develop an obesity syndrome. The anatomical basis of this syndrome is not fully clarified; inflammatory destruction of the infundibular region, vacuolar degeneration of the paraventricular nucleus of the hypothalamus and severe, progressive involution of the hippocampal formation most probably play an important role in the production of this neuroendocrine syndrome. In the acute disease, inflammatory reaction can severely aggravate virus-induced cytopathology, but cannot be the sole cause of the neurological disease, since infection with high passage virus can lead to a similarly severe disease in the absence of inflammatory changes.

Animals↗
PubMed1995

Increase of bone marrow cellularity during erythropoietin treatment in myeloma.

Treatment of myeloma-associated chronic anemia with recombinant human erythropoietin (rHuEPO) has been shown to be successful in the majority of patients. We have morphometrically investigated bone marrow sections from the iliac crest of 20 anemic myeloma patients prior to rHuEPO therapy. The 15 responding patients were re-examined after three months and, if possible, after 6 and 12 months of treatment. Significant differences were found between responders and nonresponders prior to therapy. Nonresponders presented with a pronounced shift to the right in their erythroid bone marrow cell compartment and partly with higher serum levels of endogenous erythropoietin. During rHuEPO therapy, responders showed increases in all subsets of erythropoiesis and in the total amount of hemopoietic tissue. Response was accompanied by a marked drop of serum ferritin levels, a rise in serum levels of transferrin receptors and the emptying of bone marrow iron stores; the World Health Organization performance status improved. Responders tended to present with less advanced disease stages and better performance status and showed significantly longer survival times. Loss of responsiveness to rHuEPO was observed in one patient during the terminal stage of the disease. In conclusion, morphometric examination of bone marrow biopsies during the course of rHuEPO therapy showed that the response achieved in hemoglobin values was clearly mirrored in equivalent increments of the erythroid bone marrow cell compartment.

Aged↗
PubMed1994

Rapid fluorescence in situ hybridization with repetitive DNA probes: quantification by digital image analysis.

Fluorescence in situ hybridization (FISH) has become an important tool not only in cytogenetic research but also in routine clinical chromosome diagnostics. Here, results of a quantification of fluorescence signals after in situ hybridization with repetitive DNA probes are reported using a non-enzymatic hybridization technique working with a buffer system not containing any formamide or equivalent chemical denaturing agents. Following simultaneous denaturation of both cells and DNA probes, the renaturation time was reduced to less than 30 min. For one of the DNA probes reasonable FISH-signals were even achieved after about 30 s renaturation time. In addition, the number of washing steps was reduced drastically. As a model system, two repetitive DNA probes (pUC 1.77, D15Z1) were hybridized to human metaphase spreads and interphase nuclei obtained from peripheral blood lymphocytes. The probes were labelled with digoxigenin and detected by FITC-anti-digoxigenin. The hybridization time was reduced step by step and the resulting fluorescence signals were examined systematically. For comparison the pUC 1.77 probe was also hybridized according to a FISH protocol containing 50% formamide. By renaturation for 2 h and overnight two FISH signals per nucleus were obtained. Using shorter renaturation times, no detectable FISH signals were observed. Quantification of the FISH signals was performed using a fluorescence microscope equipped with a cooled colour charge coupled device (CCD) camera. Image analysis was made interactively using a commercially available software package running on a PC (80486). For the pUC 1.77 probe the major binding sites (presumptive chromosomes 1) were clearly distinguished from the minor binding sites by means of the integrated fluorescence intensity. For the two (pUC 1.77) or four (D15Z1) brightest spots on the metaphase spreads and in the interphase nuclei hybridized without formamide, integrated fluorescence intensity distributions were measured for different renaturation times (0.5, 15, 30 min). The intra-nuclear variation in the intensity of the two brightest in situ hybridization spots appeared to be slightly higher (CV between 16 and 32%) than the corresponding variation in the metaphase spreads (CV between 10 and 19%). For the D15Z1 probe FISH signals were detected after hybridization without formamide and 15 min and 30 min renaturation. Always four bright spots were visible and tentatively assigned on the metaphase spreads (presumptive chromosome 15 and 9). The intensity variation of each pair of homologues in a metaphase spread showed a CV of 14 or 15%, respectively, for the presumptive chromosome 15, and 8 or 9%, respectively, for the presumptive chromosome 9.

Analog-Digital Conversion↗
PubMed1994

Prediction of response to erythropoietin treatment in chronic anemia of cancer.

Chronic anemia of cancer can be corrected in approximately 50% of the cases by treatment with recombinant human erythropoietin (rHuEPO). Early prediction of responsiveness would avoid the emotional and financial burden of ineffective medical intervention. Eighty patients with chronic anemia of cancer undergoing treatment with rHuEPO (150 U/kg, 3 times per week by subcutaneous injection; after 6 weeks without response, 300 U/kg) participated in this study. Response was defined as a gain of at least 2 g/dL hemoglobin (Hb) within 12 weeks. Multivariate discriminant analysis and logistic regression analysis of response were performed on routine blood tests; serum levels of EPO, iron, ferritin, transferrin, and its receptor; World Health Organization (WHO) performance status; various cytokines; neopterin; stem cell factor; C-reactive protein; and alpha 1-antitrypsin. At baseline, none of these factors showed sufficient prognostic power. The following predictive algorithm was developed: (1) If after 2 weeks of therapy both the serum EPO level is > or = 100 mU/mL and Hb concentration has not increased by at least 0.5 g/dL, unresponsiveness of the patient is very likely (predictive power, 93%); otherwise, response may be predicted with an accuracy of 80%. (2) If both the serum level of EPO is less than 100 mU/mL and Hb concentration has increased by > or = 0.5 g/dL, response is highly probable (predictive power, 95%). (3) Alternatively, a serum ferritin level of > or = 400 ng/mL after 2 weeks of rHuEPO therapy strongly indicates unresponsiveness (predictive power, 88%), whereas a level less than 400 ng/mL suggests response in 3 of 4 patients.

Adult↗
PubMed1994

Quality of life in chronic anemia of cancer during treatment with recombinant human erythropoietin.

BACKGROUND: Improvements in quality of life after treatment with recombinant human erythropoietin (rHuEPO) often have been reported in patients with end-stage renal disease. In patients with chronic anemia of cancer, comparatively few systemic investigations have been performed. METHODS: Various aspects of quality of life were self-reported on linear analogue scales of a slightly modified questionnaire that was first developed to assess toxicity of chemotherapy in patients with breast cancer. Thirty-four patients with chronic anemia of cancer completed 10 items (feelings of well-being, mood, level of activity, pain, nausea, appetite, physical ability, social activities, anxiety, and helpfulness of therapy) before and after 8 and 12 weeks of rHuEPO therapy. RESULTS: Patients with response to the therapy significantly improved after 8 weeks of treatment in some items and after 12 weeks in all items. Patients with no response also had some improvement after 12 weeks of therapy. Hemoglobin levels correlated strongly with mood and appetite. World Health Organization (WHO) performance status improved significantly in patients with response but tended to diminish in those without. Median survival was 4.1 months in patients with no response and 12.0 months in those with response. After 12 weeks of therapy, the scores of the items "physical ability" and "social activities" proved to be significant prognostic factors, which surpassed the prognostic power of the WHO performance status. CONCLUSIONS: The results of rHuEPO therapy in chronic anemia of cancer are far more than cosmetics of laboratory values. They enable the patients with response to lead a physically and socially more active life with less anxiety, brighter moods, and an increased general feeling of well-being.

Adult↗
PubMed1994

Genomic organization of Borna disease virus.

Borna disease virus is a neurotropic negative-strand RNA virus that infects a wide range of vertebrate hosts, causing disturbances in movement and behavior. We have cloned and sequenced the 8910-nucleotide viral genome by using RNA from Borna disease virus particles. The viral genome has complementary 3' and 5' termini and contains antisense information for five open reading frames. Homology to Filoviridae, Paramyxoviridae, and Rhabdoviridae is found in both cistronic and extracistronic regions. Northern analysis indicates that the virus transcribes mono- and polycistronic RNAs and uses termination/polyadenylylation signals reminiscent of those observed in other negative-strand RNA viruses. Borna disease virus is likely to represent a previously unrecognized genus, bornaviruses, or family, Bornaviridae, within the order Mononegavirales.

Amino Acid Sequence↗
PubMed1994

Glycoprotein B of bovine herpesvirus type 4: its phylogenetic relationship to gB equivalents of the herpesviruses.

In order to estimate the phylogenetic relationship of BHV-4 among the herpesviruses, we have cloned and sequenced its glycoprotein B (gB). The 2.6 kb open reading frame codes for a 874 amino acid long protein. The comparison of its deduced amino acid sequence with those of its counterparts in 19 distinct herpesviruses groups BHV-4 into the gamma-herpesvirinae. The calculation of an evolutionary tree emphasized that BHV-4 is more closely related to herpesvirus saimiri (HVS) than to Epstein-Barr virus (EBV). However, in contrast to EBV and HVS, the gB of BHV-4 contains a putative protease cleavage site and 20 potential N-glycosylation sites. The alignment of the amino acid sequences revealed that 10 cysteine and 7 proline residues, as well as the motifs SPF and GQLG, were completely conserved among the 20 investigated gBs.

Amino Acid Sequence↗
PubMed1994

Women and cancer.

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Breast Neoplasms↗
PubMed1994

Detection of Borna disease virus RNA in naturally infected animals by a nested polymerase chain reaction.

Borna disease virus in naturally infected horses, a donkey and sheep was detected for the first time by amplification of viral RNA using PCR. In contrast to a control group of healthy horses, brain tissue was positive by this assay in all animals with neurological symptoms. The use of a second round of PCR with nested primers following Southern hybridization confirmed the specificity and increased the sensitivity of the test. Comparison with conventional methods recommends this technique for monitoring of BDV infections at a molecular level.

Animals↗
PubMed1994

Sequence conservation in field and experimental isolates of Borna disease virus.

Coding and noncoding sequences were analyzed from field and experimental isolates of Borna disease virus. For a 24-kDa protein, maximum divergence was 1.5% at the predicted amino acid level and 3.1% at the nucleotide level. For a 40-kDa protein, maximum divergence was 1.1% at the predicted amino acid level and 4.1% at the nucleotide level. The highest variability in sequence (10%) was found in a 40-nucleotide stretch of genomic RNA between coding sequences for the 40- and 24-kDa proteins. The degree of sequence conservation in these isolates, passaged in various host species in vivo and in vitro over a period of 64 years, is unusual for negative-strand RNA viruses.

Animals↗
PubMed1994

Borna disease virus: immunoelectron microscopic characterization of cell-free virus and further information about the genome.

The etiological agent of Borna disease, a persistent virus infection of the central nervous system with differently expressed symptomatology, was morphologically unknown. Here we provide the first convincing data on its phenotypic architecture. Salt-released virus comprising the biological parameters of Koch's postulates has an unsegmented single-stranded RNA. A dense band (1.22 g/cm3) in CsCl contains 90-nm particles which appear to be enveloped and a fraction of 50- to 60-nm particles. Labeling of the virions with neutralizing antisera and colloidal gold conjugates indicates that the 90-nm particles most likely represent the causative agent.

Animals↗
PubMed1994

Immunological findings in patients with myelodysplastic syndrome.

Activation of monocytes and granulocytes in vitro by cytokines, in vivo administration of cytokines, as well as in vivo cytokine production due to infectious and inflammatory diseases causes changes of the surface expression density of certain membrane molecules. In recent studies we attempted to determine the feasibility of using flow cytometric immunophenotyping as a tool to develop a sensitive parameter for detecting infections at an early stage of disease when clinical parameters are still negative. Since infections are an important factor determining the clinical course of myelodysplastic syndromes (MDS), early detection of infection might be beneficial for these immunocompromised patients. We indeed found activation-associated immunophenotypic changes of cell surface antigens on monocytes and granulocytes of clinically infection free MDS patients suggesting enhanced immune activity in these patients, most likely due to latent or beginning infections. In particular, analyses of the expression density of receptors for IgG (Fc gamma Rs), complement receptors, and certain activation-associated surface molecules such as the CD67 and the M5 molecule seem to be of clinical relevance. We will also discuss findings concerning changes of cytokine levels and functional alterations of immunologic parameters in MDS patients.

Humans↗