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Biomedical subjects

H Ludwig

Publications and source records attributed to H Ludwig.

At least 289 records · Page 16Linked to original sources
PubMed1986

Shortened platelet half-life in multiple myeloma.

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half-life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained--intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.

Blood Platelets↗
PubMed1985

[Aminoglutethimide therapy in advanced breast cancer].

45 women (postmenopausal or after former oophorectomy) with metastatic breast cancer resistant to tamoxifen as well as to chemo- and radiotherapy were treated with aminoglutethimide (750 mg or 1000 mg resp. daily) and hydrocortisone (40 mg daily). Treatment resulted in 33% remissions (2 CR + 13 PR) and 53% stabilizations (24 patients) besides a non-responder rate of 13% (6 patients). Side effects (mainly central sedation, possibly exanthema, seldom anorexia, but no hematotoxicity) were observed in 13 patients (29%). Duration of remission lasted for 1 to 24 months (mean duration 10,5 months) while stabilization extended for 2 to 17 months (mean duration 7,7 months). Mechanism of action by enzymatic inhibition of the adrenal steroid hormone synthesis ("medical adrenalectomy") as well as by extra-adrenal diminution of estrogens is considered in detail. Aminoglutethimide provides effective treatment in patients with generalized metastatic breast cancer followed by best outcome in cases with osseous metastases. Clinical results are presented as an approach to successful therapy of advanced breast cancer and an endocrine alternative in tamoxifen resistance as well as a therapeutic possibility in cytotoxic induced pancytopenia.

Adult↗
PubMed1985

Acute encephalopathy associated with continuous vincristine sulfate combination therapy: case report.

Neurotoxicity is a well-recognized and commonly observed side effect associated with the use of vincristine sulfate in cancer chemotherapy. The clinical manifestations of vincristine neuropathy cover a wide spectrum of peripheral neurologic dysfunctions that have been described to be reversible and cumulative in most instances (1, 2). Paresthesias, loss of tendon reflexes, and progressive weakness are the most common clinical features (3, 4). Sensory impairment, cranial nerve palsies, gastrointestinal disturbances, and autonomic dysfunctions including atonic bladder, impotence, and orthostatic hypotension may occur (5). Acute CNS complications, usually presenting as generalized seizures, are extremely rare and only a few cases have been reported which were without underlying biochemical or structural abnormalities (1, 5-9). We describe the case of a woman with multiple myeloma, who developed fulminant encephalopathy following 4 days of continuous vincristine, adriamycin, and day 1-4 pulse dexamethasone (VAD) combination therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Bovine herpesvirus 1: differentiation of IBR- and IPV-viruses and identification and functional role of their major immunogenic components.

Infectious Bovine Rhinotracheitis (IBR) and Infectious Pustular Vulvovaginitis (IPV) virus strains of Bovine Herpesvirus 1 (BHV-1) can be differentiated by restriction endonuclease digestion of their DNAs. Antigens and polypeptide patterns of isolates of these different clinical entities are almost identical. Page analysis of immunoprecipitates revealed three major immunogenic components in BHV-1 infected cells. These are glycoproteins with apparent molecular weights of 93,000 (GP93), 74,000 (GP74) and 69,000 daltons (GP69), respectively. Bovine convalescent sera and antisera, which are directed against individual precipitates derived from crossed immunoelectrophoresis, contain antibodies reacting with one or more of these glycoproteins. The experiments with these antisera demonstrate that GP74 and possibly GP93, both structural components of the BHV-1 virion, induce neutralizing antibodies, whereas GP69, a non-structural protein, does not.

Animals↗
PubMed1985

Weekly low dose doxorubicin monotherapy in metastatic breast cancer resistant to previous hormonal and cytostatic treatment.

Weekly low dose doxorubicin monotherapy was evaluated in heavily pretreated patients with metastatic breast cancer. 19 patients received 8-12 mg/m2 doxorubicin/week for a treatment period of up to 7 months until a progression of the disease occurred (mean number of weekly courses 15 +/- 8). In 2 of 17 evaluable patients, an objective response with a duration of 3+ and 5 months respectively was achieved. In 9 patients a stabilisation of the disease was observed (mean duration of DS 4 mos +/- 2), whereas the disease progressed in 6. The tolerance for this regimen was remarkable, with neither serious acute toxicity nor any signs of congestive cardiomyopathy even in those patients who were treated beyond a cumulative dose of 450 mg/m2. Weekly low dose doxorubicin monotherapy shows modest activity, but is devoid of severe toxicity in heavily pretreated patients with metastatic breast cancer. An increase in the therapeutic index was not observed.

Aged↗
PubMed1985

Increase of virus yields and releases of Borna disease virus from persistently infected cells.

Borna disease virus grows to low titres in persistently infected cells with an infectious particle to cell ratio of 0.01 to 0.05. Inclusion of n-butyrate in the growth medium enhances infectivity yields up to 1 log. This effect is time and concentration dependent. In hypertonic medium with an excess of NaCl, KCl or Na2SO4 up to 50% of the total infectious virus yield is released from the cells. Released supernatant virus (buoyant density in sucrose rho = 1.22 g/cm3) is more heat stabile than cell-bound virus (rho = 1.18 g/cm3). The access to cell-free (released) virus opens new possibilities for the characterization of this neurotropic agent.

Animals↗
PubMed1985

Analysis of bovine cytomegalovirus genome structure: cloning and mapping of the monomeric polyrepetitive DNA unit, and comparison of European and American strains.

The genome of bovine cytomegalovirus (BCMV) strain 66-P-347 consists of double-stranded, linear DNA with a size of 144 +/- 6 kb. It contains polyrepetitive DNA (prDNA) segments like five other BCMV strains. The restriction patterns of the prDNA of all six strains are very similar and indicate that monomeric prDNA units are either 1950 bp (class I and Ia), 2350 bp (class II) or 2750 bp (class III) in size. The complete unit sequence of strain 66-P-347 (class II) was cloned in bacteriophage vector M13mp7 and mapped by the restriction enzymes EcoRI, BamHI, Bg/I, NaeI, SstII and PstI. From these results the restriction maps of the prDNA of the other five strains were deduced. The 400 bp differences in size between the three prDNA classes are a consequence of the appearance of an internal 200 bp sequence being present one-, three- or fivefold in head-to-tail formation. Hybridization of 35S-labelled recombinant phage DNA to Southern blots with DNA of the different strains leads to the conclusion that prDNA units are present as multimers in tandem formation at both genomic termini in the same orientation. The number of terminal repeat units varies between individual molecules of a strain, but the actual terminal sequences are identical.

Animals↗
PubMed1985

Isolation and characterization of a 14500 molecular weight protein from brains and tissue cultures persistently infected with borna disease virus.

A protein with an apparent molecular weight of 14500 (14.5K) was extractable from homogenates of Borna disease virus-infected brains and tissue cultures using high concentrations of detergent and salt and by differential centrifugation procedures. The protein, present in an aggregated form, was remarkably resistant to proteinase K. Specific antibodies prepared in the homologous system (rat) recognized the 14.5K protein from various sources (infected brain of rat, mouse or chicken, and tissue cultures), but did not neutralize infectivity nor stain Borna disease virus-specific antigens from in vitro or in vivo preparations. Post-infection immune sera from different animal species did not detect the protein. This 14.5K protein was infection-specific but not disease-specific, and is inferred to be part of an internal virion component.

Animals↗
PubMed1985

Phase I study of recombinant human interferon alpha-2C in patients with chemotherapy-refractory malignancies.

Twenty-two patients with advanced haemopoietic and other malignancies were treated intramuscularly with recombinant interferon-alpha 2C in a daily escalating dose. The most common side-effects were flu-like symptoms. Two patients showed severe neurotoxicity, which was completely reversible in 1 case. Doses above 30 X 10(6) IU/day were poorly tolerated and could only be achieved in a minority of the patients. Objective tumour responses were documented in malignant lymphomas, hairy cell leukaemia, and renal cell carcinoma.

Adult↗
PubMed1985

Treatment with recombinant interferon-alpha-2C: multiple myeloma and thrombocythaemia in myeloproliferative diseases.

Forty-two patients with multiple myeloma were allocated to two groups to receive either polychemotherapy with vincristine, melphalan, cyclophosphamide and prednisolone, or recombinant interferon-alpha 2C monotherapy. The response rate of 43% in the interferon group was significantly lower than that in the chemotherapy group (89%). Patients with stage I disease showed better response rates than those with stage II or stage III disease. Eleven patients with thrombocythaemia due to polycythaemia vera, chronic myeloid leukaemia or essential thrombocythaemia were treated with recombinant interferon-alpha 2C and complete remissions were achieved in 7 of the 8 evaluable patients. Side-effects were common on interferon therapy, but could be reduced by dose reduction and were reversed by cessation of treatment.

Adult↗
PubMed1985

Phase II results with recombinant interferons: renal cell carcinoma and malignant melanoma.

There is as yet no effective treatment for renal cell carcinoma and metastasizing malignant melanoma. This fact, coupled with in vitro investigations showing growth inhibitory or cytotoxic effects of interferon (IFN) on renal cell carcinoma and melanoma cell lines, led to phase II clinical trials with recombinant (r) IFN-alpha 2C and rIFN-gamma. So far 8 patients with renal cell carcinoma have been treated with IFN-alpha 2C and 3 patients with rIFN-gamma. There has been one complete response to IFN-alpha 2C, two mixed responses and one partial response. One patient on rIFN-gamma has stable disease and the other 2 have progressed. Eleven patients with metastasizing malignant melanoma were treated with IFN-alpha 2C. One patient achieved a complete remission and 3 others had stable disease which later progressed in 2 of them. Side-effects were reversible.

Adult↗
PubMed1985

Absence of autoantibodies against neurofilament proteins in the sera of scrapie infected mice.

Autoantibodies against neurofilament proteins were not detected in any of the sera from the following scrapie infected mice: 19 mice infected with scrapie agent 139A in pre-clinical stage, 32 histologically confirmed scrapie mice and other 12 clinical scrapie mice infected with various strains. The test sera were assayed against acetone-fixed central neuron cultures from fetal mice by indirect immunofluorescence and immunoperoxidase techniques. The negative result suggests that autoantibodies against neurofilament proteins do not play a role in the pathogenesis of scrapie.

Animals↗
PubMed1985

5q- chromosome in acute leukemia with lymphoid morphology and expression of myeloid membrane determinants.

We present three patients, two children and one adult, with an unusual type of acute leukemia. Whereas the blast cells showed lymphoid morphology with correlating cytochemical staining, immunological phenotyping exhibited a pure myeloid in one patient and a biphenotypic membrane marker profile in the other two patients. Cytogenetic studies revealed a 5q- chromosome as a common marker and additional individual changes. Two of the patients who were treated according to acute lymphoblastic leukemia (ALL) therapy protocols died without remission five and four weeks after diagnosis, respectively. Despite relapsing several times, another patient survived for over eight years. These three patients seem to represent one new subgroup of leukemias that can only be distinguished from typical ALL by both determination of cell surface markers and cytogenetic analysis.

Aged↗
PubMed1985

[Borna virus infection (Borna disease) in naturally and experimentally infected animals: its significance for research and practice].

In this survey article on Borna Disease-many years after the review of Zwick (1939)-again a modern comprehensive summary of "Borna Disease virus infection" is given. The infection occurs in horses and sheep, furthermore, in laboratory animal species inoculated experimentally; its clinical, virological and neuropathological features have been described in numerous presentations. Clinical symptoms in naturally and experimentally infected animals are characterized by initial alterations in the sensorium. The neurological symptomatology of the disease (disturbances in coordination, motor, sensory and vegetative symptoms) reflect the presumed localisation of the virus in various brain areas and the course of the disease supports the assumption of intraneural spread of the agent. In horses the incidence is highest during spring. Experimental infections show an exceptionally broad spectrum of infectible animals extending from higher mammals to birds. Our investigations make it clear that we have to differentiate between infections followed by disease (e.g. horse, rabbit, older rat) and persistent infections without overt clinical symptoms (mouse, chicken). Persistent infections are sometimes associated with fine alterations in behaviour (tree shrew) or decreased learning ability (mice). Borna Disease virus, which has not been characterized up to now, is known to grow without any cytopathic effect in tissue cultures. All tested cell lines (including those from man) could be infected. The investigations indicate that Borna Disease virus comprises an enveloped RNS-containing agent. The infection induces the production of specific antigens such as a complex known as the soluble antigen, and a 14500 dalton protein. Under natural conditions and in experimentally infected animals antibodies are produced against such soluble proteins and determinants involved in neutralization of the virus. In the central nervous system (CNS) a local immune response accompanied by the production of oligoclonal immunoglobulins is demonstrable. Besides the humoral reaction it was possible to study the influence of cellular defence mechanisms on the disease process in monkeys, rats and rabbits. Histopathologically, Borna Disease is characterized by a non-purulent inflammation of the brain and the spinal cord. Most alterations are found in the grey matter, mainly in the Ammon's horn, olfactory lobe, caudate nucleus, thalamus, lamina quadrigemina and in he cerebellar nuclei. The perivascular infiltrations, consisting of lymphocytes, histiocytes and plasma cells are most conspicuous. Occasionally, degenerative alterations are observed in ganglion cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

5q - marker chromosome in acute leukemia with lymphoid morphology and myeloid differentiation antigens.

We present three patients, two children and one adult, with an unusual type of acute leukemia. Whereas the blast cells showed lymphoid morphology with correlating cytochemical staining, immunological phenotyping showed a pure myeloid in one and a biphenotypic (mixed lymphoid/myeloid) membrane marker profile in two of the patients. Cytogenetic studies revealed a 5q - chromosome as a common marker with additional individual changes. Two of the patients who were treated according to ALL-therapy protocols died without remission 5 and 4 weeks after diagnosis, respectively. Despite relapsing several times, the third patient survived for over 8 years. These three patients seem to represent one new subgroup of leukemias which can only be distinguished from typical ALL by determination of both cell surface markers and cytogenetic analysis.

Aged↗