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Biomedical subjects

H Ludwig

Publications and source records attributed to H Ludwig.

At least 217 records · Page 12Linked to original sources
PubMed1990

Impaired conversion of exogenous arachidonic acid by platelets to thromboxane B2 and correction of that deficiency by interferon-alpha.

In the course of an investigation of cyclooxygenase and 12-lipoxygenase activity in platelets of patients with myeloproliferative syndrome receiving treatment with interferon-alpha 2 patients showed unusual results which have not been reported so far. Both patients had thrombocytosis, in one case associated with polycythaemia. In platelets of both patients, a reduced conversion of exogenous 14C arachidonic acid to TXB2 was observed accompanied by a shift in conversion to PGE2 and 12-HETE in one patient and to 12-HETE alone in the other before therapy. These findings were paradoxically associated with evidence of enhanced platelet activation in vivo. Treatment of both patients with interferon-alpha resulted in reversal of the biochemical abnormalities and in clinical remission.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Effect of recombinant interferon-alpha2C on reticuloendothelial function in patients with thrombocytosis.

The aim of the study was to investigate the influence of recombinant interferon-alpha 2C (rIFN-alpha 2C) on the in vivo Fc-dependent phagocytic activity of the reticuloendothelial (RE) system. Fourteen patients with excessive thrombocytosis due to myeloproliferative disorders were studied before and 3 months after initiation of therapy. RE function was determined by measuring the clearance of autologous red blood cells (RBC) labeled with 51Cr and sensitized with anti-D antibody. Eleven of the 14 patients responded to rIFN-alpha 2 treatment (platelets, less than 440 X 10(9)/liter). Rather in contrast to a shortening of platelet half-life and an increase (trendwise) in platelet-bound IgG, rIFN-alpha 2 caused a significant impairment of RE function. Although this finding could in part be accounted for by the treatment-related decrease in splenic volume, statistical analysis revealed a direct influence of rIFN-alpha 2 on RBC clearance (p less than 0.01). Our study results might be explained by an interferon (IFN)-induced, intensified expression of Fc receptors on platelet (and leukocyte) surfaces, possibly enhancing unspecific binding of IgG to their cellular membranes. The subsequent increased platelet uptake may lead to an overloading of the RE system causing impaired reactions to additional stimuli such as IgG-coated RBC.

Aged↗
PubMed1990

Recombination of genomic terminus of bovine herpesvirus type 1 with cellular DNA.

Bovine herpesvirus 1 (BHV-1) has a linear DNA genome of about 135 kb which appears as two isomers, resulting from its short unique segment being present in the two possible orientations with respect to the large unique segment. BHV-1 also circularizes its DNA to form replicative molecules. Definition of the target sequences at the genomic termini involved in the recombination events during genomic replication and isomerization, as well as virus maturation, led to the discovery that 10% of the genome molecules have additional DNA sequences attached to the right-hand terminus, as shown by electron microscopy. Three such tails have been cloned molecularly; they differ in length and nucleotide sequence, and hybridization experiments demonstrate the cellular origin of two of the three tails. The evidence presented here is consistent with a proportion of the BHV-1 genomes recombining their DNA with cellular DNA during lytic infection.

Animals↗
PubMed1990

Interferon-alpha-induced morphological changes of megakaryocytes: a histomorphometrical study on bone marrow biopsies in chronic myeloproliferative disorders with excessive thrombocytosis.

Interferon(rIFN)-alpha, a successful therapeutic agent in the control of thrombocytosis, has been shown to suppress human megakaryopoiesis. We investigated bone marrow biopsies from 12 patients with thrombocytosis due to chronic myeloproliferative disorders. Prior to treatment as well as during rIFN-alpha-2c therapy, several morphometric parameters of megakaryopoiesis were evaluated. Megakaryocyte density decreased significantly in all patients, megakaryocyte size decreased in polycythaemia vera, agnogenic myeloid metaplasia, and essential thrombocythaemia, but increased in chronic myeloid leukaemia. The various changes observed during therapy indicate an inhibitory effect of rIFN-alpha-2c on megakaryopoiesis and suggest a selective influence on megakaryocytes at various stages of maturation. Increased numbers of pyknotic (bare) nuclei may reflect a shortening of megakaryocyte life-span. No remarkable changes were found in the fibre content of the bone marrow.

Aged↗
PubMed1990

Genomic termini of equine herpesvirus 1.

After cell infection with the equine herpesvirus 1 (EHV-1), the termini of the linear double-stranded DNA genome fuse to form circular forms. To investigate the mechanisms in the generation and cleavage of such replicative-form DNAs, the genomic termini, the fusion of termini from replicative-form molecules, and the junction between the short and long genome segments have been analyzed by restriction mapping, blot hybridizations, cloning, and sequencing. The data suggest that the genome ends are not redundant and that the genomic termini are fused in replicative intermediates via 3' single-base extensions at the termini of the unique long segment (UL) and terminal repeat (TR). Adjacent to the EHV-1 termini are AT and gamma sequence elements highly conserved among different herpesviruses. We propose that both of these sequence elements are important for the cleavage of EHV-1 replicative forms.

Animals↗
PubMed1990

[Erythropoietin treatment of tumor-associated anemia in patients with multiple myeloma].

Anemia of malignancy is a complication of neoplastic disease which causes impairing symptoms and often requires blood transfusions. In this clinical trial, we have treated 13 patients suffering from chronic anemia of malignancy and multiple myeloma with recombinant human erythropoietin (rHuEPO) three times a week. Eleven patients responded to the treatment by appropriate increases of their hemoglobin levels and the eventual correction of the anemic state, one non-responding patient had to terminate the treatment early because of transfusion requirements. Under rHuEPO therapy, the evaluated parameters of iron metabolism indicated the enhanced synthesis of hemoglobin. The symptoms of anemia subsided in the responding patients and most of them reported a hightened subjective sense of well-being. No adverse side effects, particularly no episodes of hypertension, were observed in any patient.

Aged↗
PubMed1990

Heterogeneity of serological responses in paucibacillary leprosy--differential responses to protein and carbohydrate antigens and correlation with clinical parameters.

We have examined the serological responses of 154 untreated paucibacillary (PB) leprosy patients to two carbohydrate and one protein antigens of Mycobacterium leprae. There was a heterogeneous response with 20% of PB patients having IgM anti-PGL-I antibodies and a similar proportion with IgG anti-LAM antibodies, while 33% had antibodies to the M. leprae-specific epitope on the 35-kDa protein. There was overlap in the responses such that 43% of the patients were seropositive in one of the two M. leprae-specific assays, while 49% were positive in any assay. There was a gradation in seropositivity with increasing extent of disease for each of the clinical parameters measured. Those with established disability at the time of presentation were more likely to be seropositive in each assay.

Adolescent↗
PubMed1990

[Subspecialization in gynecology--pro and con].

To discuss the problem of subspecialization in gynecology is very popular at present. Whether or not a complete separation into the three subdisciplines, (1) materno-fetal medicine--obstetrics, (2) surgical gynecology--gynecologic oncology, and (3) gynecologic endocrinology--reproductive medicine, is recommendable remains unclear. Some authors describe forms of supplementary postgraduate education only, a kind of prolongation of the basic gynecologic and obstetric training concentrating on one of the three main fields. The complete separation, i.e. into obstetric medicine, reproductive medicine, and gynecologic pelvic surgery, has the advantage of a more effective concentration on each of the respective subdisciplines in clinical work and in research. On the other hand, the separation will produce several disadvantages: (a) that which falls between the subdisciplines will be difficult to integrate; (b) the principle of the gynecologist functioning as a primary health care physician for women will be weakened, i.e. his competence in family-planning, pregnancy and delivery, cancer screening for genital and breast tumors, cycle disorders, pelvic inflammatory diseases and the care of postmenopausal women; (c) the lectures will become more split or overloaded with details than at present; (d) the need for a cost-effective and widely available general gynecologic care will not be met, and (e) the opportunities for younger colleagues to have an office of their own will be restricted. The disadvantages outweigh the advantages. The solution might be a combination of the two competitive models: the creation of subdisciplines, completely separated from one another but for a minority only (i.e. to candidates for leading posts in clinics of the tertiary care, university hospitals etc).(ABSTRACT TRUNCATED AT 250 WORDS)

Austria↗
PubMed1990

Long-term alpha-interferon therapy in myelodysplastic syndromes.

The myelodysplastic syndrome (MDS) is characterized by a high probability of leukemic transformation and frequently lethal infections or bleeding episodes. Up to now, no generally accepted form of therapy has been established for MDS. Previous trials with alpha-interferon (IFN-alpha) have shown some beneficial effects. We studied the effects of long-term application of IFN-alpha at higher dosages in patients with "low-risk" MDS. Ten patients were included in the study; eight were treated for a period of 6-36 months. IFN-alpha was administered at a median dosage of 9, 6, 4 mU/week during the first, second, and third year, respectively. Response was determined by the status of peripheral blood and bone marrow. Prolonged exposure to IFN resulted in a response rate of 3/10 (30%). In an additional case, disease progression was retarded during the third year of therapy. The incidences of infections and bleeding events subsided notably. After the withdrawal of IFN, hematological and clinical parameters rapidly deteriorated in some patients. The observed improvement of the patients' susceptibility to infections possibly prolongs their survival and seems to justify further trials on IFN treatment in patients with MDS.

Aged↗
PubMed1989

Long-term interferon therapy for thrombocytosis in myeloproliferative diseases.

31 patients with thrombocytosis associated with myeloproliferative disorders were included in a prospective trial of long-term interferon therapy. 6 patients (19%) had side-effects which required withdrawal of interferon within one year. 22 patients (71%) achieved and maintained a complete response (platelet count less than 440 x 10(9)/l) for at least twelve months, with reduction or abolition of symptoms associated with thrombocytosis and a significant fall in bone-marrow megakaryocytes. At twelve months, 25 patients were randomly allocated to maintenance or withdrawal of interferon. Thrombocytosis recurred rapidly when treatment was stopped, but a second remission could be achieved by resumption of interferon therapy.

Aged↗
PubMed1989

Early-onset thrombocytopenia during combination chemotherapy in testicular cancer is induced by vinblastine.

Platelet kinetics were studied in 70 patients with testicular cancer to elicit the agent responsible for chemotherapy-induced transient early-onset thrombocytopenia; 204 treatment courses were analyzed using three different therapy protocols, which contained vinblastine and bleomycin either alone or in combination with cisplatin. Platelet count decreased significantly from the start of vinblastine administration reaching its nadir on the third day of therapy in each of the three treatment groups. Between day 4 and day 10 of the treatment cycle, platelet counts steadily increased even in patients still receiving continuous bleomycin infusions. The conclusion that the observed early-onset thrombocytopenia was caused by vinblastine was substantiated by the outcome of two additional examinations. Platelet half-life was significantly shortened 24 hours after vinblastine administration and electron microscopy revealed a dissolution of cytoplasmatic microtubules with loss of the typical discoid shape of platelets within 15 minutes after the start of therapy. Both findings occurred irrespective of the specific treatment protocol, i.e., even after nothing but vinblastine had been given. These results strongly suggest that vinblastine is the main cytostatic agent responsible for the transient early-onset thrombocytopenia observed during chemotherapy of testicular cancer.

Adolescent↗
PubMed1989

Learning deficiencies in Borna disease virus-infected but clinically healthy rats.

Borna disease (BD) virus, a still unclassified neurotropic agent, causes either fatal encephalomyelitis or persistent asymptomatic infection in a variety of animal species. We monitored the neuronal functions of intracerebrally infected but healthy rats with three types of learning experiments. Spatial discrimination learning, using the y maze and the hole board, was significantly less successful in BD virus-infected (I) compared with mock-infected (M) rats. Similarly, I rats tended to show a certain emotional disturbance (reduced resting behavior and less anxiety) as evaluated by open-field and neophobia tests. Furthermore, in two aversive learning experiments (taste aversion and reaction suppression via Skinner box), it appeared that the I rats expressed a significantly diminished ability to learn pain avoidance compared with M rats. In conclusion, we found specific learning deficiencies together with subtle behavioral alterations suggesting that BD virus causes certain modulations of high integrative brain functions which are only detectable under experimental conditions.

Animals↗
PubMed1989

Mapping of epitopes on the 65k DNA-binding protein of herpes simplex virus type 1.

Previously we have described the isolation of seven monoclonal antibodies (MAbs) and two polyvalent rabbit sera directed against the product of herpes simplex virus type 1 (HSV-1) gene UL42, a 65K DNA-binding protein (65KDBP) which is essential for HSV DNA replication and virus growth. We now report the synthesis of all 483 overlapping hexapeptides of this 488 amino acid protein and describe their use for the identification of epitopes recognized by these MAbs and polyvalent sera. MAb 6898, derived from one fusion, recognizes the peptides EDLDGA and DLDGAA which correspond to amino acids 363 to 369 of 65KDBP. MAbs Z4D4, Z6F3, Z1A8, Z10Cl, Z3H12 and Z1F11, derived from a second fusion, all recognize the peptides GDPEDL and DPEDLD which correspond to amino acids 360 to 366. As expected both polyvalent sera recognize several different epitopes.

Amino Acid Sequence↗
PubMed1989

A bovine herpesvirus (BHV-4) as passenger virus in ethmoidal tumours in Indian cattle.

A herpesvirus was isolated from tumours of the ethmoidal mucosa in two of three head of cattle in the State of Kerala, India. The virus designated M40 was cytopathic for a variety of cultured bovine and porcine cells and it did not kill suckling mice or chicken embryos. Sera from tumour-bearing cattle and goats reacted with the M40 virus. Immunofluorescence tests with FITC-conjugated IgG from a bovine monospecific antiserum to bovine herpesvirus 4 (BHV-4) stained the M40 virus specific antigen in infected cells. Experimental infection of goats with the M40 virus did not result in development of tumours. This virus is therefore considered to represent a "passenger" virus. A great similarity was found between restriction patterns of DNAs extracted from M40 virus and the strain 66-P-347, a reference strain of the BHV-4 group.

Animals↗
PubMed1989

Phase II evaluation of 5-fluorouracil, folinic acid and cisplatin in advanced-stage colorectal adenocarcinoma.

Twenty-seven patients with advanced measurable colorectal carcinoma were treated with a combination protocol consisting of folinic acid (FA) 200 mg/m2 i.v. bolus followed by 5-fluorouracil (5-FU) 550 mg/m2, and cisplatin (CIS) 20 mg/m2 each administered as a 2-hour i.v. infusion. Treatment was given on 4 consecutive days at 3- to 4-weekly intervals. Of 25 evaluable patients, 1 achieved complete remission and 5 partial remission for an overall response rate of 24%, while 9 patients (36%) had stable disease. Two out of 6 responders had previously progressed on 5-FU-containing regimens. The 95% confidence interval for response is 7-41%. Median survival time for all 27 patients enrolled in the study is 27+ weeks. Tolerance was remarkable and consisted primarily of mild and reversible gastrointestinal symptoms and myelosuppression. This 3-drug-regimen had significant palliative activity in our patient population. Its definitive role in the treatment of metastatic colorectal cancer as well as the potential improvement of the therapeutic index of 5-FU/FA by addition of CIS, require further evaluation in a randomized phase III trial.

Adenocarcinoma↗