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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 127 records · Page 7Linked to original sources

Treatment of brain metastases in patients with small-cell lung cancer: lessons from treatment of other tumors.

Brain metastases are common in patients with small-cell lung cancer (SCLC) and are usually fatal. About half of all patients who develop brain metastases will remain symptomatic at their time of death, even if the immediate cause of death is not neurologic. While it has been argued that the obtundation that sometimes comes with brain metastases may be a relatively easy way to die, studies which have examined the quality of life of individuals developing brain metastases dispute this. For most patients and their families, the impairment of physical, cognitive, and affective function which accompanies most brain metastases is highly distressing and can be seen as a "loss" of the patient even before his/her death. Thus, improved treatment of overt brain metastases will be of palliative value, and eradication of microscopic disease in the brain may cure patients whose disease in other sites has been eradicated. Prophylactic cranial irradiation (PCI) for patients who have achieved a complete response to induction therapy markedly reduces the risk of central nervous system relapse and modestly but significantly improves survival. Despite the use of PCI, many patients with SCLC will develop brain metastases, and there is increasing interest in surgical treatment of patients with solitary lesions and the use of systemic chemotherapy in treating patients, with both SCLC and non small-cell lung cancer, who have multifocal brain metastases which are minimally symptomatic, particularly when these patients also have extracranial metastatic disease.

Journal Article↗

[Differential diagnosis and therapy of acute abdomen in sickle cell crisis. A rare case in visceral surgery].

Surgical therapy of the acute abdomen often allows only limited time for differential diagnosis to confirm the indication for surgery. Under consideration of clinical aspects and case history both common and rare causes of an acute abdomen should be investigated without undue loss of time. Differential diagnostic considerations and eventual therapy are presented in the following case of a 25-year-old Afro-american who developed multiorgan failure after an initial course of lower-back pain. In addition to the clinical setting of an acute abdomen the patient presented with acute respiratory failure and laboratory signs of severe hemolysis in combination with newly detected splenomegaly. The indication for splenectomy was made following CT-proven complete splenic infarction due to repeated acute squestration. Histologic examination of the spleen together with hemoglobin electrophoresis confirmed the clinical assumption of unusually late primary manifestation of a sickle cell crisis. In the underlying case, the hemoglobinopathy was in fact the less common form of combined sickle-cell-beta-thalassemia. A ten-day course of intensive care therapy was necessary to treat ongoing multiorgan failure due to persistent sickle cell crisis. Current diagnostic and therapeutic procedures in connection with sickle cell crisis as a rare cause of an acute abdomen with the necessity for surgical intervention are presented.

Abdomen, Acute↗

[Detection of mammaglobin mRNA as a marker for circulating tumor cells in breast carcinoma].

Mammaglobin (hMAM) has been shown to be a marker for the detection of circulating tumor cells in the peripheral blood (pB) of breast cancer (BC) patients via a nested RT-PCR assay. 286 samples from BC patients were classified into four defined clinical subgroups: prior to and after surgery (pre, post), no evidence of disease (NED) and metastatic disease (MD). hMAM mRNA expression was detected in 2/46 pre (4%), 2/24 post (8%), 4/135 NED (3%) and 35/81 MD (43%) patients. 68 BC patients with NED and negative for hMAM mRNA in their pB were repeatedly tested for at least 6 months. Fifteen of these patients relapsed. Eight of them were hMAM-positive, 5 at time of relapse, one patient 13 months before and two patients 10 and 17 months after relapse was diagnosed. 7/15 BC patients relapsed within 24 months, 5 of them were hMAM-positive versus 3 of 8 patients with later relapses. On the basis of these preliminary results we conclude that tumor cells can be detected via hMAM nested RT-PCR in the pB of BC patients and that hMAM could be a marker for early relapse.

Adult↗

Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells.

Activation of antigen-presenting cells (APCs) by invariant constituents of pathogens such as lipopolysaccharide (LPS) or bacterial DNA (CpG-DNA) initiates immune responses. We have analyzed the mitogen-activated protein kinase (MAPK) pathways triggered by CpG-DNA and their significance for cytokine production in two subsets of APCs, i.e. macrophages and dendritic cells (DCs). We found that CpG-DNA induced extracellular signal-regulated kinase (ERK) activity in macrophages in a classic MEK-dependent way. This pathway up-regulated tumor necrosis factor production but down-regulated interleukin (IL)-12 production. However, in DCs, which produce large amounts of IL-12, CpG-DNA and LPS failed to induce ERK activity. Consistent with a specific negative regulatory role for ERK in macrophages, chemical activation of this pathway in DCs suppressed CpG-DNA-induced IL-12 production. Overall, these results imply that differential activation of MAP kinase pathways is a basic mechanism by which distinct subsets of innate immune cells regulate their effector functions.

Animals↗

Development of calretinin immunoreactivity in the brainstem auditory nuclei of the barn owl (Tyto alba).

The early development of calretinin immunoreactivity (CR-IR) was described in the auditory nuclei of the brainstem of the barn owl. CR-IR was first observed in the auditory hindbrain at embryonic day (E17) and a day later (E18) in the inferior colliculus. In each of the auditory nuclei studied, CR-IR did not develop homogeneously, but began in the regions that map high best frequencies in the adult barn owl. In the hindbrain, CR-IR was first observed in the rostromedial regions of the cochlear nucleus magnocellularis and the nucleus laminaris, and in the dorsal regions of the nucleus angularis and in the nucleus of the lateral lemniscus. In the inferior colliculus, CR-IR began in the ventral region of the central core. The edge of these gradients moved along the future tonotopic axes during the development of all nuclei studied, until adult patterns of CR-IR were achieved about a week after hatching.

Animals↗

Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group.

BACKGROUND: Prophylactic cranial irradiation reduces the incidence of brain metastasis in patients with small-cell lung cancer. Whether this treatment, when given to patients in complete remission, improves survival is not known. We performed a meta-analysis to determine whether prophylactic cranial irradiation prolongs survival. METHODS: We analyzed individual data on 987 patients with small-cell lung cancer in complete remission who took part in seven trials that compared prophylactic cranial irradiation with no prophylactic cranial irradiation. The main end point was survival. RESULTS: The relative risk of death in the treatment group as compared with the control group was 0.84 (95 percent confidence interval, 0.73 to 0.97; P= 0.01), which corresponds to a 5.4 percent increase in the rate of survival at three years (15.3 percent in the control group vs. 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased the rate of disease-free survival (relative risk of recurrence or death, 0.75; 95 percent confidence interval, 0.65 to 0.86; P<0.001) and decreased the cumulative incidence of brain metastasis (relative risk, 0.46; 95 percent confidence interval, 0.38 to 0.57; P<0.001). Larger doses of radiation led to greater decreases in the risk of brain metastasis, according to an analysis of four total doses (8 Gy, 24 to 25 Gy, 30 Gy, and 36 to 40 Gy) (P for trend=0.02), but the effect on survival did not differ significantly according to the dose. We also identified a trend (P=0.01) toward a decrease in the risk of brain metastasis with earlier administration of cranial irradiation after the initiation of induction chemotherapy. CONCLUSIONS: Prophylactic cranial irradiation improves both overall survival and disease-free survival among patients with small-cell lung cancer in complete remission.

Adult↗

Stabilizing function of skeletal muscles: an analytical investigation.

Stability is the ability of a system to return to its original state after a disturbance. Taking vertical oscillations of the centre of mass of a human bending his legs as an example we prove that the intrinsic mechanical properties of musculature can stabilize the oscillatory movement (preflex) without reflexive changes in activation. The human is represented by a model consisting of a massless two-segment linkage system (knee) topped by a point mass. Conditions for stability are calculated analytically based on the theory of Ljapunov and the results are illustrated by numerical examples. In order to guarantee a self-stabilizing ability of the muscle-skeletal system, the muscle properties such as force-length relationship, force-velocity relationship and the muscle geometry must be tuned to the geometric properties of the linkage system.

Animals↗

Immunostimulatory CpG-oligodeoxynucleotides cause extramedullary murine hemopoiesis.

Bacterial DNA and the synthetic CpG-oligodeoxynucleotides (ODNs) derived thereof have attracted attention because they activate cells of the adaptive immune system (lymphocytes) and the innate immune system (APCs) in a sequence-dependent manner. Here, we addressed whether CpG-ODNs affect hemopoiesis. Challenging mice with immunostimulatory CpG-ODN sequences led to transient splenomegaly, with a maximum increase of spleen weight at day 6. The induction of splenomegaly by CpG-ODNs was sequence-specific, dose-dependent, and associated with an increase in splenic cell count, in numbers of granulocyte-macrophage CFUs (GM-CFUs), and early erythroid progenitors (burst-forming units-erythroid). The transfer of spleen cells from CpG-ODN-pretreated animals into lethally irradiated syngeneic mice yielded an increase of spleen CFUs. Furthermore, the challenge of sublethally irradiated mice with CpG-ODNs caused radioprotective effects, in that recovery of GM-CFUs and cytotoxic T cell function was enhanced. The increase in GM-CFU and CTL function correlated with an enhanced resistance to Listeria infection in irradiated mice. We conclude from these data that CpG-ODNs trigger extramedullary hemopoiesis, and that this finding could be of therapeutic relevance in myelosuppression.

Adjuvants, Immunologic↗

Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide.

BACKGROUND: For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy. METHODS: We studied 417 patients with limited small-cell lung cancer. All the patients received four 21-day cycles of cisplatin plus etoposide. We randomly assigned these patients to receive a total of 45 Gy of concurrent thoracic radiotherapy, given either twice daily over a three-week period or once daily over a period of five weeks. RESULTS: Twice-daily treatment beginning with the first cycle of chemotherapy significantly improved survival as compared with concurrent once-daily radiotherapy (P=0.04 by the log-rank test). After a median follow-up of almost 8 years, the median survival was 19 months for the once-daily group and 23 months for the twice-daily group. The survival rates for patients receiving once-daily radiotherapy were 41 percent at two years and 16 percent at five years. For patients receiving twice-daily radiotherapy, the survival rates were 47 percent at two years and 26 percent at five years. Grade 3 esophagitis was significantly more frequent with twice-daily thoracic radiotherapy, occurring in 27 percent of patients, as compared with 11 percent in the once-daily group (P<0.001). CONCLUSIONS: Four cycles of cisplatin plus etoposide and a course of radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results in patients with limited small-cell lung cancer.

Adult↗

Use of traditional drugs in a hospital of Chinese medicine in Germany.

The frequency of use of traditional Chinese drugs was investigated in relation to Western and Chinese diagnostic classifications in a hospital for traditional Chinese medicine in Germany. All 1597 in-patients treated in the hospital between February 1992 and August 1993 entered a prospective observational study. About two thirds of the patients suffered from chronic pain syndromes, the most frequent single diagnosis being migraine (n=244). All patients were treated with at least one of four Chinese therapies (traditional Chinese drugs, acupuncture, Tuina-massage, Qi-gong). 95.1% of all patients received traditional Chinese drug treatment, prescribed in complex prescriptions including 3 to 12 single drugs from a total of 305. Drug patterns prescribed to patients with the same Western diagnosis tended to be similar, but could differ strongly for single drugs in subgroups with distinct Chinese diagnoses. Studies evaluating traditional Chinese treatment strategies in patients classified according to Western nosology should take into account possible diagnostic differences according to Chinese nosology. The development of a reliable coding system for Chinese diagnostic classifications is a precondition for further cross-cultural studies.

Journal Article↗

The resistance against Listeria monocytogenes and the formation of germinal centers depend on a functional death domain of the 55 kDa tumor necrosis factor receptor.

The biological functions mediated by the death domain of the 55-kDa tumor necrosis factor receptor (TNFRp55) in vivo are still elusive. TNFRp55 mutants lacking a functional death domain were expressed in TNFRp55-/- and in TNFRp55+/- mice as transgenes under control of the H-2Kb promoter. Analysis of these animals revealed that signals originating from the TNFRp55 death domain are indispensable for the protection against Listeria monocytogenes, the expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the spleen and the development of splenic germinal centers. Furthermore, the transgenic coexpression of the TNFRp55 mutants in TNFRp55+/- mice exerts a dominant negative effect on the signaling of the endogenous receptor chains in vivo.

Animals↗

CpG-oligodeoxynucleotides co-stimulate primary T cells in the absence of antigen-presenting cells.

CpG-containing oligodeoxynucleotides (CpG-ODN) act as powerful adjuvant during in vivo induction of T cell responses. While CpG-ODN directly activate antigen-presenting cells (APC) and thus exert an extrinsic activity on T cells, it is unclear whether they directly affect T cells (intrinsic activity). Here we analyze the effects of CpG-ODN on T cells in an APC-free cell culture. We report that CpG-ODN co-stimulate T cells provided they were triggered via their TCR. CpG-ODN induced IL-2 production, IL-2 receptor expression and thus proliferation. Proliferation was blocked by cyclosporin A or anti-IL-2 monoclonal antibodies (mAb) but not by anti-IL-4 mAb. Moreover, CpG-co-stimulated T cells differentiated into cytolytic T lymphocytes in vitro. Of note, IL-2-driven growth of primed T cells was not affected by CpG-ODN. Co-stimulation was also operative in T cells from CD28-/- mice and in TCR-transgenic T cells stimulated with peptide. CpG-ODN-mediated co-stimulation of T cells in vitro may thus explain part of the potent adjuvant effects of CpG-ODN in vivo.

Adjuvants, Immunologic↗

Guanosine-rich oligodeoxynucleotides induce proliferation of macrophage progenitors in cultures of murine bone marrow cells.

Widely used to specifically inhibit gene expression, synthetic oligodeoxynucleotides (ODN) can exert a plethora of non-antisense effects. Immunostimulation by CpG-ODN has attracted particular attention. ODN rich in the nucleotide guanosine (G-rich ODN) constitute another type of sequences displaying non-antisense-mediated effects. We have examined the effects of CpG- and G-rich ODN on primary mouse bone marrow cells (BMC) in vitro. CpG-ODN induced rapid proliferation of B cells and production of IL-6 and IL-12p40. However, when tested in agar colony assays, CpG-ODN failed to promote the formation of colonies. In marked contrast, G-rich non-CpG-ODN led to sustained proliferation of macrophage-like cells without inducing cytokines or hemopoietic growth factors. Unlike CpG-ODN, G-rich ODN effectively induced the formation of macrophage colonies in agar assays, indicating a direct action on progenitor cells. Electrophoretic mobility shift assays revealed specific binding of G-rich ODN to a non-nuclear protein. The ability of a panel of ODN to compete for binding correlated with their potential to induce proliferation of macrophage-like cells from primary mouse BMC. As such, these data reveal a so far unrecognized potential of G-rich ODN to signal directly outgrowth of macrophage progenitors from BMC.

Agar↗

MRI of bone marrow: opposed-phase gradient-echo sequences with long repetition time.

Signal intensity for opposed-phase gradient-echo (GE) sequences of tissues composed of fat- and water-equivalent cells such as red bone marrow is extremely sensitive to variation of the ratio of both cell populations (fat-to-water ratio QF/W). Because most bone marrow pathology results in variation of QF/W, GE sequences are characterized by high-contrast imaging of pathology. The aim of this study was to evaluate the influence of TR, TE, FA, QF/W and histology on signal intensity. Signal intensity of opposed-phase GE sequences as a function of TR, TE, FA, and QF/W was measured for a fat-water phantom and cadaver specimens of normal bone marrow (red and yellow) and pathological bone marrow (tumors). All specimens were correlated to histology. Opposed-phase GE imaging of red bone marrow pathology results in low-signal-intensity imaging of intact red bone marrow and high-signal-intensity positive contrast imaging of pathology associated with a change in QF/W. In first-order approximation the signal intensity of pathology is linearly correlated to the change in QF/W. Opposed-phase GE imaging is a sensitive imaging technique for red bone marrow pathology. Relative contrast of red bone marrow pathology is similar to fat-suppressed imaging techniques. Acquisition time is identical to T1-weighted SE sequences.

Bone Marrow↗

Selective defects of T lymphocyte function in patients with lethal intraabdominal infection.

BACKGROUND: In recent models, compensatory antiinflammatory immune reactions triggered in response to systemic inflammation were considered important for the outcome of sepsis. The present study investigated T-cell functions in patients with postoperative sepsis due to intra-abdominal infection. METHODS: Peripheral T cells were purified from 32 sepsis patients and 41 healthy controls. Proliferation and production of interferon (IFN)-gamma, interleukin (IL)-2, IL-4, tumor necrosis factor (TNF), and IL-10 were stimulated by cross-linking of CD3 and CD28. RESULTS: T-cell proliferation and production of IL-2 and TNF were severely suppressed in patients with lethal intraabdominal infection as compared with survivors and healthy controls. Sepsis survivors showed normal T-cell proliferation and IL-2 release, whereas secretion of TNF was reduced. However, TNF suppression in survivors was less severe than in nonsurviving patients. Defective T-cell functions were observed at the onset of sepsis and persisted throughout the entire observation period. T-cell production of IL-4 and IL-10 was not affected by postoperative intraabdominal infection. CONCLUSIONS: Defective T-cell proliferation and secretion of IL-2 and TNF correlate with sepsis mortality, thus indicating an important role of T 'cells for the immune defense against postoperative infection. Immune defects were evident at the onset of sepsis, suggesting that immunosuppression may develop as a primary response to sepsis without preceding immune hyperactivity.

Abdomen↗

On the mechanism of action of plant adaptogens with particular reference to cucurbitacin R diglucoside.

Cucurbitacin R diglucoside (DCR), one of the active principles of Bryonia alba L. root was found to have an effect on the production of corticosteroids and the biosynthesis of eicosanoids in the adrenal cortex, isolated adrenocortical cells, blood plasma, and leukocytes under stress and stress-free conditions in vitro and vivo. DCR prevents stress-induced alterations of eicosanoids in blood and moderately stimulates the adrenal cortex to adapt organism to stress, because a moderate increase in corticosteroid secretion protects the defense system of organisms from becoming hyperactive. DCR enhances sensitivity to stress due to the effects of eicosanoids and corticosteroids.

Adaptation, Physiological↗