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Biomedical subjects

H Ludwig

Publications and source records attributed to H Ludwig.

At least 127 records · Page 7Linked to original sources
PubMed1996

Interleukin-6 and tumor necrosis factor alpha levels after bisphosphonates treatment in vitro and in patients with malignancy.

Bisphosphonates are potent inhibitors of bone resorption and are widely used in the treatment of bone diseases. One of the side effects of administered aminobisphosphonates is transient fever and some biological changes that are suggestive of an acute phase response. Pamidronate [(3-amino-1-hydroxypropylidene).1, 1-bisphosphonate] and ibandronate [1-hydroxy-3-(methylpentylamino) propylidenebisphosphonate] incubated in heparinized whole blood at doses of 10(-4) and 10(-5) mol/L, induced the production of tumor necrosis factor alpha (TNFalpha). Moreover, pamidronate was found to slightly stimulate interleukin-6 IL-6 production. In contrast, clodronate (dichloromethylenebisphosphonate) did not increase IL-6 or TNFalpha. To investigate these phenomena in vivo, acute phase reaction was assessed in patients with malignant disease treated with 60 mg of pamidronate (n = 29), 1500 mg of clodronate (n = 8), or 0.5-2 mg of ibandronate (n = 6), all given intravenously. A significant decrease in lymphocyte and leukocyte count was observed in the pamidronate group. In the same group, seven patients (24%) showed a transient increase of body temperature above 37 degrees C with an increase > or = 0.5 degrees C at 24 h. These changes were not found in the patients treated with clodronate or ibandronate. Plasma IL-6 and TNFalpha levels increased significantly after pamidronate treatment, whereas no change was seen after clodronate infusion. The peak of IL-6 level (53.7 +/- 14.1 [SEM] pg/mL) was observed at 24 h, and that of TNFalpha level (26.9 +/- 3.4 pg/mL) at 48 h after the beginning of pamidronate administration (values before treatment, respectively: 28.6 +/- 7.1 pg/mL, p < 0.006; and 13.1 +/- 1.5 pg/mL, p = 0.0001). The peak of C-reactive protein (CRP) level was found at 48 h (41.0 +/- 7.8 vs. 25.5 +/- 5.6 mg/L before treatment, p < 0.01) and CRP levels were strongly correlated with IL-6 levels (p = 0.65,p < 0.001). Only one patient treated with ibandronate showed an increase in IL-6 and CRP levels. Patients treated with pamidronate, whose body temperatures were increased at 24 h, had a greater increases of circulating IL-6, TNFalpha, and CRP at 24 h and 48 h than patients without temperature increase. These results suggest that pamidronate treatment, but not clodronate and possibly not ibandronate at the doses used, induced an increase in the plasma levels of IL-6 and TNFalpha, which may be responsible for the acute phase reaction observed clinically.

Aged↗
PubMed1996

Activation of human neutrophils after contact with cellulose-based haemodialysis membranes: intracellular calcium signalling in single cells.

PURPOSE OF STUDY: In vitro contact of human leukocytes with cellulose-based dialysis membranes under complement-independent conditions results in activation of various leukocyte functions. To analyse signals involved in the mechanism of cell activation, we measured changes in cytosolic free calcium ([Ca2+]i) in individual human blood neutrophils (PMN) upon contact with flat sheet haemodialysis membranes. RESULTS: By confocal laser-scanning microscopy (CLSM), changes in [Ca2+]i were monitored in Fluo-3-labelled cells up to 10 min after contact with a regenerated cellulose (RC) membrane. Multiple [Ca2+]i transients were observed for cells in contact with RC; biostochastic analysis showed that up to 67% of the PMN responded with a high increase in [Ca2+]i, the rest were low- or non-responding cells. After contact with the new synthetic polycarbonate-polyether (PC-PE) membrane only non-responding cells were seen, indicating reduced cellular contact activation. The increase in [Ca2+]i of cells on RC could be inhibited by 5mM L-fucose. This monosaccharide was recently found to be present in cellulose-based polymers in picomolar concentrations. CONCLUSIONS: The data supports the hypothesis that dialysis-membrane-associated L-fucose residues participate in complement-independent leukocyte activation during haemodialysis therapy.

Biocompatible Materials↗
PubMed1996

Serum immunoreactive bone sialoprotein as a new marker of bone turnover in metabolic and malignant bone disease.

Bone sialoprotein (BSP) is a phosphorylated glycoprotein with a M(r) of 70-80 kDa that accounts for approximately 5-10% of the noncollagenous proteins of bone. Due to its relatively restricted distribution to mineralized tissues, BSP may serve as a potential marker of bone metabolism. Employing a recently developed RIA, serum BSP was measured in 133 healthy subjects, aged 20-80 yr, and in patients with primary hyperparathyroidism (pHPT; n = 26), Paget's disease of bone (PD; n = 14), untreated multiple myeloma (MM; n = 32), and breast cancer with bone metastases (BC; n = 19). Results were compared to clinical and laboratory data, including serum total alkaline phosphatase as a marker of bone formation, and the urinary cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone resorption. In healthy adults, serum BSP values ranged between 5.0-21.6 ng/mL (5-95% interval), with a median of 10.5 ng/mL (total group). In healthy females, a linear correlation was found between serum BSP and age (r = 0.51; P < 0.001), with significantly higher values in postmenopausal than in premenopausal women (13.3 +/- 4.8 vs. 9.0 +/- 3.8; P < 0.01). In the healthy group, BSP values did not change with body mass index, lumbar bone mineral density, serum calcium, serum creatinine, or serum total alkaline phosphatase levels. In contrast, a weak, but significant, correlation was observed between serum BSP and the urinary excretion of PYD and DPD. Compared to those in healthy controls, serum BSP levels were significantly higher in patients with pHPT, PD, MM, or BC (P < 0.01 for all groups). These differences remained after analyses were adjusted for age and sex. In pHPT, serum BSP levels were closely correlated to urinary PYD and DPD (r = 0.87 and 0.83, respectively; P < 0.01), whereas in PD, no correlation was observed between any of the bone markers. Serum BSP levels were highest in patients with MM, and there was a significant difference between early and advanced stages of the disease (30.2 +/- 8.0 vs. 64.3 +/- 6.8; P < 0.01). In a subgroup of 15 patients with metastatic BC, iv bisphosphonate treatment resulted in a rapid reduction of serum BSP levels to 40% of the baseline values within 4 days of treatment. In conclusion, BSP appears to be a sensitive marker of bone turnover, and the present data suggest that its serum levels predominantly reflect processes related to bone resorption.

Adult↗
PubMed1996

[Dysmenorrhea].

Primary dysmenorrhea is very frequent in ovulating women; it can even become a disease. In some cases, but not always, it is preceded by premenstrual tensions. Secondary dysmenorrhoea should be clearly differentiated, because it is a symptom of uterine abnormalities or adnexal diseases, whereas primary dysmenorrhoea is an entity in itself. The most frequent cause of secondary dysmenorrhoea is endometriosis. Dysmenorrhea membranacea is a rare event, but should not be forgotten. Primary dysmenorrhea involves the entire organism and the psyche of the suffering woman. The problem is its cyclic repetition and everlasting painful expectation. The pathogenesis is more clarified now but nevertheless not yet completely investigated. There is evidence that under the dominating role of sexual hormones paracrine sequelae are occurring, which result in a local increase of prostaglandins. The most important factor is the rhythmic ischemic reaction due to vasoconstriction in small arteries of the uterine wall, causing excruciating pains at times. The treatment is different whether or not children are immediately desired. Oral contraception and progestogens are useful when given days before the onset of menstruation. If the ovulatory cycle should be maintained, the drugs of choice are non-steroidal antiinflammatory preparations, among them naproxen and ibuprofen the most effective. Since those drugs exert side-effects when administered over a long period of time, alternatives must be available. The most appropriate ones are ASS, magnesium, calcium antagonists or tocolytic agents. Few new approaches to further alternative therapies (neuro-stimulation) could not provide a decrease of the uterine contractility in cases of primary dysmenorrhea.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

[History of gynecologic treatment of infertility].

Within less than 20 years this branch of the infertility treatment by new reproductive medical technologies has left behind the original concept of bypassing blocked tubes. It has started to bypass nature. As the extracorporal way, however of shortest duration within the human prenatal development, exposes the human being to external influences, the discussion about the pros and cons of the new technologies is already abundant and still rising. The field named infertility-treatment was once in the middle and in the heart of the gynecologic discipline. It gave rise to the most intellectual branch of gynecology, the gynecologic endocrinology. Undoubtedly, there are tendencies at present to make "Reproductive Medicine" an independent discipline splitting from gynecology and obstetrics, with only the core remaining gynecology, but with the addition of essential constituents coming from genetics, human biology, andrology, medical ethics, even from sociology and law. Gynecology would tremendously suffer from this loss. The field "Reproductive Medicine" has gained the most attentive audience far beyond the scope of our gynecologic profession. One thinks it should have calm and peace to grow further in the same way other fields of medicine flourish, guided by science, concience and compassion. The juxta-medical expansion of the field could as well not have been foreseen one-hundred years ago.

Europe↗
PubMed1996

[Emergencies in obstetrics].

The survey on emergencies in Obstetrics is addressed here to practitioners and advanced medical students. The specialized gynecologist will, however, find some case reports interspersed illustrating what he/she has already experienced sometimes. The paper should be a refreshment for them. Acute abdominal pain in pregnancy challenges the diagnostic skills of the physician first contacted. Is it, what causes the pain, appendicitis as is frequently in nonpregnant young women, or gall-bladder disease as in the elderly obese, or even dangerous intestinal obstruction, or is the pain deriving from a twisted pedicle of an occult ovarian cyst or is it simple gastrointestinal discomfort? Putting into account the differing frequency of incidences of disease does not always help. Emergency may arise from the rarest event. With increasing traffic on our streets blunt trauma occurs and it might hurt pregnant women as well as their fetus. Even seat-belts can cause damages, if pelvic belts are used instead of shoulder belts. Traumata from accidents are often associated to immediate shock. Shock in pregnancy poses different questions according to the physiology of the progressing pregnancy. There is a variety of shock etiologies. Bleeding from the vagina is the most common complaint. Those can be harmless or they can be the first and leading sign of imminent danger to the fetus and the mother. Diagnosis does not allow any delay. One of the most striking complications in late pregnancy is described by the acronym "HELLP"-syndrome [hemolysis, elevated liver enzymes, low platelets]. This syndrome is a critical complication of preeclampsia. One third of the cases occur after delivery. It has not yet been clearly decided whether active management including immediate delivery by cesarean section in disregard of the maturity of the child, or the conservative approach with intensive care, drastic antihypertensive medication and additional serial plasmapheresis might prove to be more efficient in terms of live-saving for mother and child. The mortality of mothers suffering from HELLP remains to be high, the perinatal mortality is even higher. Post partum hemorrhage is due to the lack of contractibility of the uterus after overdistension, protracted labour, malpositions, mere inertia etc., from lacerations, or from placental retention. It is always an emergency with hemorrhagic shock impending. The risk situation around even normal birth is well known. Emergencies will appear every time unannounced. There are post partum risks as well; they should not be underestimated when home-delivery is desired.

Abdominal Injuries↗
PubMed1996

First isolates of infectious human Borna disease virus from patients with mood disorders.

Borna disease virus (BDV), an unique type of non-segmented negative-stranded enveloped RNA virus, is known as an animal pathogen that causes behavioral diseases in higher vertebrates. Past studies have found antibodies to BDV as well as BDV proteins and genomic transcripts in peripheral blood mononuclear cells (PBMCs) of infected animals and human psychiatric patients. Here, we present the first isolation of infectious BDV from such patients' PBMCs. Isolation attempts were conducted with randomly collected PBMC samples from 33 psychiatric inpatients, by co-cultivation and long-term passaging with a human cell line. BDV isolates were identified by infectivity, analysis of viral antigens, sequencing of one viral gene, and successful infection of animals. Three individual isolates could be recovered. They originated from two bipolar patients with acute depression, and one patient with a chronic obsessive-compulsive disorder. Rescue of human BDV required PBMC samples with strong viral antigen expression, and at least 11 subcultures per sample. Genetic and biological properties point to a close relationship of human and animal strains, but also to the uniqueness of each human isolate. Isolation of BDV from patients with major mood disorders at a time of acute depression strengthens the possibility that BDV infection is one of the environmental factors that contributes to recurrent depressive illnesses in man. These isolates represent the first three defined strains of the infectious human BDV.

Adult↗
PubMed1995

Recombinant human erythropoietin for the correction of cancer associated anemia with and without concomitant cytotoxic chemotherapy.

BACKGROUND: Chronic anemia is a common complication in patients with cancer, especially in those with advanced disease or who are under intensive chemotherapy. Because homologous blood transfusions involve some hazards, the safety and efficacy of recombinant human erythropoietin (r-HuEPO) in the treatment of anemic patients with cancer with and without concomitant chemotherapy were studied. METHODS: One-hundred two cancer patients with hemoglobin less than 11 g/dl, ferritin greater than 30 micrograms/l, and creatinine < 220 mumol/l were enrolled in the study, 94 were eligible for efficacy evaluation. Sixty-eight patients received chemotherapy (CT group) and 26 had no cytotoxic cancer treatment (NT group). Recombinant human erythropoietin was administered subcutaneously at a dose of 150 U/kg three times per week for 6 weeks; in nonresponders the dose was doubled for the subsequent 6 weeks. Response was defined as the achievement of a hemoglobin increase of 2g/dl. Clinical and laboratory parameters, including serum erythropoietin (EPO) levels, performance status, and quality of life, were investigated at baseline and monitored at regular intervals thereafter. RESULTS: Response was achieved by 52% and 62% of CT and NT patients, respectively. The highest response rates were observed in patients with lung cancer or with a histology of squamous cell carcinoma (both 80%). In responding patients, the symptoms of anemia subsided. They no longer needed blood transfusions after 4 weeks of therapy; and both their performance status and quality of life improved significantly. The NT patients achieved slightly more favorable results on lower weekly doses: 450 U/kg/week in NT versus 570 U/kg/week in CT patients. Serum EPO levels were higher in nonresponders at baseline and further increased during the course of treatment. Recombinant human erythropoietin was well tolerated by all patients. CONCLUSION: This multicenter study in a large patient collective shows that r-HuEPO treatment represents a safe and effective means to increase the red cell mass and eliminate the need for blood transfusions in approximately 50% of the patients with chronic anemia of cancer. Responding patients not only have increased levels of hemoglobin, but their performance status also improves significantly, and they enjoy a significantly enhanced quality of life.

Adult↗
PubMed1995

Interphase fluorescence in situ hybridization identifies chromosomal abnormalities in plasma cells from patients with monoclonal gammopathy of undetermined significance.

Karyotypic studies in patients with monoclonal gammopathy of undetermined significance (MGUS) have been hampered by a low percentage of bone marrow plasma cells (BMPC), which are predominantly nonproliferating. By combining cytomorphology and interphase fluorescence in situ hybridization (FISH) we investigated whether or not chromosomal abnormalities occur in BMPC from patients with MGUS. Studying chromosomes 3, 7, 11, and 18, which we found to be frequently aneuploid by FISH in multiple myeloma (MM), we observed three hybridization signals for one of these chromosomes 3 were most common, occurring in 38.9% of patients, followed by gains of chromosomes 11 (25%), 7 (16.7%), and 18 (5.6%) Among BMPC, the frequency of aneuploid cells was 18.9% +/- 13.9% (mean +/- SD) for chromosome 3, 22.3% +/- 9.2% for chromosome 11, 23.2% +/- 22.0% for chromosome 7, and 6.1% +/- 2.3% for chromosome 18. In five patients, chromosomal abnormalities were shown to be restricted to BMPC expressing cytoplasmic immunoglobulins corresponding to the serum paraprotein. No gain of hybridization signals was observed in normal and reactive plasma cells. In one patient with MGUS, metaphase cytogenetics revealed one abnormal metaphase with 47, XY, +4, and trisomy 4 was also demonstrated in a subpopulation of BMPC by interphase FISH. FISH results from patients with MGUS and newly diagnosed MM at stage IA (n = 14) indicated that aberrations involving > or = 2 chromosomes occurred significantly more often in early stage MM (P < .01). With respect to clinical and laboratory features, MGUS patients with and without chromosomal abnormalities were indistinguishable. Our results indicate that MGUS already has the chromosomal characteristics of a plasma cell malignancy.

Adult↗
PubMed1995

Immunoreactivity of the central nervous system in cats with a Borna disease-like meningoencephalomyelitis (staggering disease).

The inflammatory cell composition and the expression of major histocompatibility complex (MHC) antigens in the central nervous system (CNS) of 13 cats with a spontaneous, Borna disease-like meningoencephalomyelitis (staggering disease) was investigated by immunohistochemistry with a panel of monoclonal and polyclonal antibodies. T lymphocytes were the predominating inflammatory cells within the adventitial space. CD4+ T cells were more abundant than CD8+ T cells. Scattered IgG-, IgA- and IgM-containing cells were found in the adventitial space and surrounding neuropil, often adjacent to neurons. There was a markedly increased MHC class II expression in cells morphologically resembling microglia. In several cats, Borna disease virus specific antigen was detected, but only in a few cells, mainly of macrophage character. Our findings indicate a long-standing inflammatory reaction in the CNS of cats with staggering disease, possibly triggered and sustained by a persistent viral infection.

Animals↗
PubMed1995

L-fucose residues on cellulose-based dialysis membranes: quantification of membrane-associated L-fucose and analysis of specific lectin binding.

Contact of mononuclear human leukocytes with cellulose dialysis membranes may result in complement-independent cell activation, i.e. enhanced synthesis of cytokines, prostaglandins and an increase in beta 2-micro-globulin synthesis. Cellular contact activation is specifically inhibited by the monosaccharide L-fucose suggesting that dialysis membrane associated L-fucose residues are involved in leukocyte activation. In this study we have detected and quantitated L-fucose on commercially-available cellulose dialysis membranes using two approaches. A sensitive enzymatic fluorescence assay detected L-fucose after acid hydrolysis of flat sheet membranes. Values ranged from 79.3 +/- 3.6 to 90.2 +/- 5.0 pmol cm-2 for Hemophan or Cuprophan respectively. Enzymatic cleavage of terminal alpha-L-fucopyranoses with alpha-L-fucosidase yielded 7.7 +/- 3.3 pmol L-fucose per cm2 for Cuprophan. Enzymatic hydrolysis of the synthetic polymer membranes AN-69 and PC-PE did not yield detectable amounts of L-fucose. In a second approach, binding of the fucose specific lectins of Lotus tetragonolobus and Ulex europaeus (UEAI) demonstrated the presence of biologically accessible L-fucose on the surface of cellulose membranes. Specific binding was observed with Cuprophan, and up to 2.6 +/- 0.3 pmol L-fucose per cm2 was calculated to be present from Langmuir-type adsorption isotherms. The data presented are in line with the hypothesis that surface-associated L-fucose residues on cellulose dialysis membranes participate in leukocyte contact activation.

Acrylic Resins↗
PubMed1995

Pressure effects on the stability of lipoxygenase: Fourier transform-infrared spectroscopy (FT-IR) and enzyme activity studies.

Fourier transform infrared spectroscopy (FT-IR) studies of lipoxygenase at pressures of up to 1.2 GPa have shown changes in the amide I' band which correlate to structural changes of the enzyme. The shift of the frequency maximum of the amide I' band at about 600 MPa suggests a cooperative change in the secondary structure of the protein. Studies of the changes in band width have shown the structural changes at 600 MPa to be irreversible. This has been confirmed by studies of enzyme activity after pressure treatment: exposure to 600 MPa for 30 min (40 degrees C) clearly reduced the activity of lipoxygenase. Anodic gel electrophoresis under non-denaturating conditions revealed a decrease in native protein parallel to the activity loss. A pressure-temperature-phase diagram for soybean lipoxygenase was established.

Enzyme Stability↗
PubMed1995

Prognostic factors in endometrial cancer.

OBJECTIVE: Most patients with endometrial carcinoma present with stage I disease and it is this group of patients in which prognostic factors have been studied, so that therapy can be tailored to the risks for recurrence. The papillary serous endometrial cancer and clear cell cancers have a poor prognosis but these comprise only a small proportion of endometrial cancer patients. The current surgical staging system for endometrial cancer is based on previously identified intra and extra-uterine factors that influence the prognosis. However, much of the information regarding prognosis, such as histologic type and grade, evidence of disease beyond the uterus and receptor-status can be gleaned from careful preoperative assessment of these patients. Information regarding ploidy and receptor status is available from curettage specimens and, with increasing use of hysteroscopy and/or vaginal ultrasound a more precise assessment of the extent of the disease in the uterine cavity and involvement of the cervix may be possible, although the uterine extent of the disease does not play the prognostic role that was anticipated formerly. A major concern regarding surgical staging has been the fact that many of these patients are elderly and obese with significant medical problems. There is the imminent risk that the pelvic and para-aortic node dissection (rather than sampling) may increase morbidity. More studies have shown that this might not be a factor with sampling. But does it suffice? Similarly, concerns have been expressed regarding those patients who may require postoperative radiation which may be compromised by postoperative adhesions, bladder, intestine and ureteral problems. It is yet to be demonstrated that in diseases extending outside the pelvis, the currently available treatment affects survival. Undoubtedly, recurrence patterns will be affected but clear demonstration of survival advantage is not available, eventually will never be. The concepts of treatment of advanced disease with spread outside the pelvis should undergo rethinking in the way that control of the existing disease rather than eradicating it by all means might offer better chances for life quality, life expectancy albeit limited, in cancer patients.

Age Factors↗
PubMed1995

Borna disease virus genome transcribed and expressed in psychiatric patients.

Borna disease virus (BDV) is a neurotropic, negative and single-stranded enveloped RNA virus that persistently infects various domestic animal species. Infection causes disturbances in behaviour and cognitive functions, but can also lead to a fatal neurologic disease. Human infections seemed likely, since serum antibodies were detected in neuropsychiatric patients. Further proof came from our discovery that peripheral blood monocytes carry viral antigens. Here, we present the first data on different viral genomic transcripts in such patients' cells as well as sequence data of transcripts. Both viral markers seem to coincide with acute episodes of mood disorders, thus pointing to a new human virus infection possibly threatening mental health.

Acute Disease↗
PubMed1995

Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer.

BACKGROUND: Treatment results in patients with metastatic renal cell cancer (RCC) are still extremely unsatisfactory. Rates of response to IFN-alpha monotherapy and/or IL-2 mono/combination therapy vary between 10% and 20%. Coumarin (Cum) together with cimetidine (Cim) has yielded objective responses in 20%-33% of patients with RCC, according to two recent phase II studies. PATIENTS AND METHODS: In the present study 148 patients with metastatic RCC were randomised to receive either IFN-alpha (5 MU 5 x weekly s.c.) + coumarin (100 mg/d p.o.) + cimetidine (3 x 400 mg/d p.o.), or IFN-alpha-monotherapy (5 MU 5 x weekly s.c.). RESULTS: Of the 148 patients in the study 137 were evaluable for response. No differences in remission rates (RR IFN-alpha + Cum + Cim 17.1% and IFN-alpha 20.8%) or survival times (median survival 9 months and 8 months, respectively) were found between these two treatment arms. CONCLUSIONS: This study confirms that INFN-alpha has antitumoral activity in RCC. Adding coumarin + cimetidine to IFN-alpha in the dose and regimen prescribed in this study did not increase response rates or survival.

Adult↗