Interleukin-6 is a prognostic factor in multiple myeloma.
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Humans↗
Biomedical subjects
H Ludwig
Publications and source records attributed to H Ludwig.
An experimental study on the pathogenicity of the caprine herpesvirus type 1 (CHV-1).
The pathogenicity of caprine herpesvirus type-1 (CHV-1) in goat kids and lambs was studied. Two experiments were carried out. In the first, two Saanen goat kids and four lambs of a local breed were infected intravenously with the Swiss strain E/CH of the virus. Clinical reaction was severe in the kids, but it was very mild in the lambs. Virus was excreted from the kids in higher titres and longer than in lambs. Virus was also isolated from tissue specimens but only from a kid that died on post inoculation day 4 (PID 4). The gross- and histopathological lesions were more severe in kids. In the second experiment only lambs were used. They were dexamethasone treated and then virus inoculated. A very mild infection developed. The lambs did not shed the virus, neither the virus was isolated from their tissues collected at necropsy. Nevertheless histopathological lesions were seen. In both experiments the animals seroconverted on PID 10.
Animals↗
Simian agent 8--a herpes simplex-like monkey virus.
This review summarizes the most recent information on Simian Agent 8, a herpes simplex-like monkey virus. The agent has a broad host range and--besides the classical morphogenesis (budding at the internal nuclear membrane)--the virus gets enveloped at all cytoplasmic membranes including the plasma membrane; strikingly it carries a rather prominent tegument. Regarding its sequence arrangement SA8 can be grouped to the E-type genomes. It has a G + C-content of 69% and a total DNA-homology with HSV-1 of 31%. The glycoproteins gC and gE are largely type-specific; whereas gB and gD as well as ICP35, ICP8 and the major capsid protein represent well conserved proteins of the simplexviruses. The type-common epitopes of gB and gD induce cross-reacting antibodies, which are even involved in cross-neutralization.
Animals↗
Biological and molecular aspects of bovine herpesvirus 4 (BHV-4).
This review summarizes most recent information on the bovine cytomegalovirus BHV-4. The virus is not associated with clearly defined clinical entities in cattle. It can easily be isolated in tissue culture and has a broad host range. BHV-4 strains are rather similar in restriction enzyme analysis of their DNAs, the size of the pr DNAs, however, differs. The genome represents a gamma-herpesvirus. Because of its uniqueness BHV-4 is discussed as an appropriate vector.
Animals↗
Borna disease virus-specific antigens: two different proteins identified by monoclonal antibodies.
A variety of cells originating from different species, including man, can be infected with Borna disease (BD) virus. Two different virus infection-specific antigens with molecular weights of 24 kD and 35/38 kD (double band) could be demonstrated using antigen preparations from persistently infected cells and rat brains, and polyvalent antisera from naturally and experimentally infected animals. Three different monoclonal antibodies were selected. One was specific for the 24-kD protein and two others reacted with the 35/38-kD antigen. The 24- and 35/38-kD antigens could be monitored concomitantly with the appearance of newly synthesized infectious virus. Both antigens could be detected at the same time during the infection cycle, and showed identical distribution in the cell. Their relationship to one another and their possible function is discussed.
Animals↗
MDR1 gene expression and prognostic factors in primary breast carcinomas.
To prospectively assess the role of the MDR1 gene in breast carcinomas, MDR1 RNA levels of breast carcinoma specimens were determined by slot blot analysis. In 59 evaluable patients with primary breast carcinomas, MDR1 RNA levels of the carcinomas were negative in 54%, low in 29% and high in 17% of the patients. No differences in age, menopause status, oestrogen and progesterone receptor levels, tumour size, lymph node involvement and c-erbB-2/neu gene expression were observed between MDR1 RNA negative patients and MDR1 RNA positive patients.
Adult↗
Interferon alfa-2b with VMCP compared to VMCP alone for induction and interferon alfa-2b compared to controls for remission maintenance in multiple myeloma: interim results.
The present trial was designed to evaluate whether interferon (IFN) combined with standard induction chemotherapy and/or interferon remission maintenance treatment improve treatment results in patients with multiple myeloma. Up to now 89 patients have received IFN plus vincristine/melphalan/cyclophosphamide/prednisolone (VMCP) as induction therapy, and 86 conventional VMCP. The proportion of patients with progressive disease was significantly lower (P less than 0.005) under IFN + VMCP as compared to the VMCP treatment group. Survival times were significantly longer (P less than 0.02) after IFN + VMCP induction therapy than after VMCP alone. In the second phase of this investigation, 33 progression-free myeloma patients were assigned to receive IFN as maintenance therapy, and 41 patients served as untreated controls. Patients maintained with IFN showed a tendency towards increased progression-free survival. Haematological side effects were observed significantly more often in patients receiving IFN, with more severe haematological toxicity in patients on the combined IFN + VMCP regimen and an increased number of patients with mild haematological toxicity in the group maintained with IFN. Other side effects, such as fever and fatigue, remained within tolerable limits. In conclusion, the preliminary results of this current clinical trial indicate significant advantages of combined IFN + VMCP induction treatment in terms of reduced disease progression and prolonged survival and possible benefits of IFN maintenance therapy in patients with multiple myeloma.
Adult↗
Conserved domains of glycoprotein B (gB) of the monkey virus, simian agent 8, identified by comparison with herpesvirus gBs.
The herpesvirus simian agent 8 (SA8) gene which corresponds to the herpes simplex virus (HSV) gene encoding glycoprotein B (gB) was localized, cloned and sequenced. Comparison of its deduced amino acid sequence with those of its counterparts in 12 other distinct herpesvirus was used to evaluate their homology and phylogenetic relationship. The results emphasized that SA8 gB is more closely related to those of HSV-1 and -2, and bovine herpesvirus 2 than to the homologous proteins of other herpesviruses. Furthermore, the alignment showed several regions of domains conserved in the closely related sequences, including four conserved in all the herpesvirus gB sequences examined. The conservation of 10 cysteine residues and most of the proline residues, as well as several potential N-glycosylation sites, suggested that the secondary and tertiary structures of these gBs were similar.
Amino Acid Sequence↗
Interferon in essential thrombocythaemia.
In the present investigation, 20 patients with ET were treated with recombinant interferon alfa-2c (IFN) for up to 4 years. Initially, IFN was administered subcutaneously at a dosage of 6-45 MU/week. The dosage was adjusted according to individual tolerance and response. The median dose during induction was 20 MU/week, 10 MU/week during the remaining first year, 6 MU/week during the second year and 2 MU/week thereafter. 13 patients (65%) achieved complete remission (platelet count less than 440/nl), four patients (20%) had partial remission (greater than 440/nl but a reduction by more than 50% of the initial count). The median platelet count remained steady throughout the 4-year period of treatment, in spite of extreme dose reductions. After withdrawal of IFN, however, platelet counts again increased. The white blood cells showed a marked decrease similar to that of platelet counts, whereas the haemoglobin level remained fairly stable. In the bone marrow, a significant decrease in megakaryocyte density and size could be observed. Concurrently with the improvement of haematological parameters, clinical symptoms improved, but reappeared after withdrawal of IFN. During induction, fever, bone and/or muscle pain, fatigue, lethargy and psychological symptoms were the most prominent side-effects in the majority of patients. In three patients these symptoms led to discontinuation of the treatment. With repeated dose reductions, excellent long-term tolerance was achieved, and during late maintenance treatment the only observed side-effect was an induction of thyroid autoimmunity in three patients. IFN is an effective, well-tolerated alternative in the long-term treatment of symptomatic ET. However, since withdrawal of IFN leads to recurrence of thrombocytosis, continued treatment is to be recommended.
Adult↗
Microarchitecture of the human endometrium by scanning electron microscopy: menstrual desquamation and remodeling.
Twenty-two hysterectomy specimens were collected over a period of two decades in order to investigate the morphological sequence of menstrual desquamation and its consecutive remodeling of the endometrium. The technique used was described earlier by H. Ludwig and H. Metzger (1976). Scanning electron microscopy is the only way to illustrate and describe the microarchitecture of the endometrial surface. At the beginning of the menstrual bleeding, glandular stumps surviving the desquamation of the layer functionalis stick out from the debris at the top of the basal layer. Fibrin mesh formation, the liberation of lysosomes, and the emigration of white blood cells and macrophages, both being already present in the midluteal endometrial stroma, can be observed. They are interrelated with the clearance of the menstrual wound. Coincidentally with the process of desquamation the re-epithelization starts and takes the first four to six days of the normal cycle. The events are illustrated by selecting specimens of uteri from women with comparable data but from different days of the normal cycle. Surprisingly transitory excess formation of epithelial outgrows (micropolyps) are observed. They disappear later in the cycle, some might persist and form micropolyps, which will be the source of occasional intermenstrual bleeding--so far the polyps are vascularized. The endometrial surface is covered de novo by a lining surface epithelium at the sixth day. Ciliogenesis occurs within this epithelium. Other ciliated cells emanate from the glandular epithelium. In early stages of menstrual regeneration the growth pattern of the epithelial monolayer forming the lining surface in spiral traces according to their origination from the circle-structures of the endometrial glands. Before the incoming menstrual break-down small crevices, clefts or defects appear within the lining surface endometrium, a few white blood cells, enriched in the stroma around the vessels, might even reach the surface. The apical membranes of several non-ciliated cells exhibit rounded leaks, others show ruptures. It is the tissue break-down around the superficial endometrial vessels, what creates the onset of menstrual blood flow. In the very early preparations of the bleeding endometrium those opened capillary vessels could be identified.
Cell Cycle↗
Effect of combination chemotherapy with verapamil.
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Adult↗
[Euthanasia--limits of therapy in oncology from the physician's viewpoint].
The Hippocratic oath, which includes refraining from the prescription of deadly drugs or giving advice on suicide still remains the cornerstone of medical ethics. Therefore, any active fostering of the dying process has to be strictly rejected. Nevertheless, in caring for cancer patients, many borderline situations arise in which serious decisions about the continuation of a treatment regimen are called for--decisions basically equating to a choice between prolonging life or allowing death. As long as the patient is able to do so, he himself must decide and the physician has to respect his decision. However, often the patient is unable to determine his own fate. No easy general recommendations can be offered for such situations. The physician has to consider the specific characteristics of the disease and take into account the patient's individual needs. Then, for each case anew, a careful, conscientious decision has to be made and the physician must take personal responsibility for its consequences. In spite of treatment successes, death cannot be conquered, but only postponed. This knowledge helps the physician to recognize more clearly the realistic possibilities of medical aid and to empathically help the dying patient.
Attitude of Health Personnel↗
Erythropoietin treatment of anemia associated with multiple myeloma.
Anemia is a common complication of multiple myeloma. It resolves early in the disease if chemotherapy induces a complete remission, but persists if the disease progresses, causing disabling symptoms and often requiring blood transfusions. We treated 13 patients with myeloma-associated anemia by administering recombinant human erythropoietin three times a week for six months. Eleven patients (85 percent) had steady increases in hemoglobin levels and eventual correction of the anemia. Their symptoms of anemia subsided, and they reported a heightened sense of well-being. No patient had any adverse side effects, particularly episodes of hypertension. Monitoring of the serum M component showed a predominantly stable tumor load without apparent interaction between the underlying disease and the response to erythropoietin therapy. The number of erythroid burst-forming units in the bone marrow and peripheral blood and the level of erythropoiesis in bone marrow smears increased significantly during therapy. Pretreatment serum levels of erythropoietin were higher in the patients who did not respond and in those who required more than two months of treatment before they responded. Serum iron, ferritin, and transferrin concentrations reflected responses to treatment. We conclude that recombinant human erythropoietin is a promising therapeutic tool for treating myeloma-associated anemia.
Aged↗
Reversal of multi-drug resistance in human KB cell lines by structural analogs of verapamil.
Several structural analogs of verapamil were studied for their ability to reverse multi-drug resistance (MDR) in human KB cell lines. D595, D792 and verapamil completely reversed resistance to colchicine and adriamycin. D595 and D792 had a higher reversing potency than verapamil. Devapamil, gallopamil, emopamil and D528 partially reversed MDR. The reversing potency of a drug did not correlate with its calcium antagonistic activity. No differences in reversing potency between (R)-isomers, (L)-isomers and the racemic forms were observed in the case of both verapamil and emopamil. (R)-verapamil, which has less calcium antagonistic activity and less in vivo toxicity than racemic verapamil, and D792, which has higher reversing potency and less in vivo toxicity than racemic verapamil, should be suitable for clinical applications to overcome drug resistance in cancer patients.
Cell Survival↗
Conserved epitopes of simian herpesvirus SA 8 and bovine herpesvirus type 2.
Some major structural components of simian herpesvirus SA 8 were analyzed and the relationship of SA 8 with HSV-1 and especially with BHV-2 was further characterized using a panel of SA 8- and BHV-2-specific monoclonal antibodies directed against gB, gD, gE, and ICP 8. It could be shown that SA 8 and BHV-2 expressed gB-1 equivalents, which differ in electrophoretic mobility, but share common epitopes with HSV-1. The antigenic determinants were detectable in the cytoplasm, on the surface of infected cells and on the virus envelope. Monoclonal antibodies reactive with epitopes of gB-SA 8 and gB-BHV-2 neutralized the homologous virus and cross-neutralized only HSV-1 and HSV-2, suggesting differences in accessibility of the corresponding epitope on SA 8 and BHV-2, respectively. A second protein with conserved epitopes on SA 8, BHV-2, and HSV-1 was identified as ICP 8. This nucleus associated protein was additionally detected on the envelope of SA 8 and HSV-1. The results imply that ICP 8 might have a function not only in virus replication, but also in virus assembly. We could furthermore define type-specific epitopes on two SA 8 envelope proteins which are analogous to gD-1 and gE-1, respectively. The gD-specific epitope induced a type-specific neutralizing antibody, making it interesting for differentiation of closely related herpesviruses.
Antibodies, Monoclonal↗
Sequential high-dose methotrexate, 5-fluorouracil, and doxorubicin for treatment of advanced pancreatic cancer.
A phase II trial of sequential high-dose methotrexate, 1500 mg/m2, and 5-fluorouracil, 1500 mg/m2 intravenously on day 1, plus doxorubicin, 30 mg/m2 i.v. on day 14, has been undertaken in patients with locally advanced or metastatic adenocarcinoma of the pancreas. Of 25 evaluable patients there were 1 complete response and 3 partial responses for an overall response rate of 16% (95% confidence interval 5%-36%). The median survival of all patients was 6.7 months (range 1-17 months). There was one treatment-related death due to pancytopenia and sepsis. In all other patients therapy was generally well-tolerated. We conclude that this combination protocol has only modest activity in the treatment of advanced pancreatic cancer.
Adult↗
Experimental treatment of chronic lymphocytic leukemia with extracorporeal photochemotherapy. Initial observations.
Based on the encouraging results obtained with extracorporeal photochemotherapy (EP) in the treatment of the exfoliative erythrodermic form of cutaneous T-cell lymphoma (CTCL), leukemic form, as well as other T-cell-mediated diseases we evaluated the therapeutic potential of EP in patients with chronic lymphocytic leukemia (B-CLL). Three patients with B-CLL were treated for a period of 1 year. Two patients showed stabilization of disease, as demonstrated by reduction in their peripheral white blood cell count, with one patient showing lymph-node resolution. A third patient with significant intolerance to previous chemotherapy did not respond within the observed period. No significant side effects of EP were observed. Our observations suggest that EP may have a positive effect on the course of B-CLL in selected patients. Additional clinical trials are warranted to further define the role of EP alone or in combination therapy in the management of B-CLL.
Adult↗
Immunoprotection of implantation.
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Embryo Implantation↗