The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

The origin and nature of osteoclast-like multinucleated giant cells (OMGCs), in extraskeletal neoplasms, is uncertain. The ultrastructure, antigenic phenotype and function of OMGCsm in a breast carcinoma were studied in order to clarify the relationship between OMGCs, osteoclasts and other cells of the mononuclear phagocyte system (MPS). OMGCs resorbed cortical bone in a manner similar to osteoclasts. However, unlike osteoclasts, OMGCs did not possess a ruffled border or clear zone, and expressed HLA-DR and Fc receptors and CD14, CD16, CD18 and CD11 (p150,95) antigens. In addition, OMGCs failed to respond morphologically to calcitonin and were directly stimulated by parathyroid hormone (PTH) to increase bone resorption. These findings suggest that OMGCs are a specific type of macrophage polykaryon distinct from both osteoclasts and other types of inflammatory polykaryon. Occasional smaller (20-25 microns) macrophage-like cells were also associated with resorption pits. Bone resorption by OMGCs isolated from the breast indicates that a cell of the MPS can be transplanted to a new tissue location and perform a highly specialised function appropriate to an MPS cell of that tissue (i.e. the osteoclast). PTH stimulation of bone resorption by OMGCs suggests that PTH or a PTH-like protein, may be involved in the bone resorption and consequent hypercalcaemia associated with metastatic breast cancer.     

Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

QT prolongation under sevoflurane in infants

Introduction   QT interval prolongation may cause the potentially lethal tachyarrhythmia torsades de pointes ( 1 ). The cause of the QT interval prolongation may be a congenital mutation in genes encoding cardiac potassium and sodium channels ( 2 ) or be acquired following drug administration ( 3 ) or metabolic disorders ( 4 ). Among a few other drugs volatile anaesthetics prolong the QT interval. During the last few years sevoflurane has become the most used volatile anaesthetic for the induction of anaesthesia in infants.
Methods   This investigation, on infants aged from 1 to 6 months, was approved by the institutional ethic committee. Thirty-six otherwise healthy infants due to elective surgery were included in our study The patients were randomly assigned to one of two treatment groups. Group S ( n  = 24) was anaesthetised with sevoflurane, Group H was anaesthetised with halothane. ECG recordings were taken before the anaesthesia onset, 15 min after the first contact with the volatile anaesthetic and 60 min after the ending of the volatile gas exposition. QTc interval was calculated using the Bazett's formula ( 5 ).
Results   QTc interval was significantly ( P < 0.0002) (Table 1) lengthened 15 min after anaesthesia induction with sevoflurane as well as 60 min ( P < 0.01) after the ending of the gas exposition without any difference in age and gender. The QTc interval in patients anaesthetised with halothane did not show any significant change.  

  Table 1     

824.

Effect of nedocromil on bronchospasm induced by inhalation of substance P in asthmatic subjects   总被引：3，自引：0，他引：3  

N Crimi  F Palermo  R Oliveri  B Palermo  C Vancheri  R Polosa  A Mistretta 《Clinical allergy》1988,18(4):375-382

Several studies have demonstrated that neuropeptides are present in peptidergic fibres of bronchial tissue. The aim of the present study was to evaluate in vivo the effect of nedocromil sodium (2 x 2 mg) on bronchospasm induced by inhalation of substance P. Six moderate asthmatic patients, mean age 25.17 years, were studied. Airway response was measured as FEV1 and the dose of substance P (using a dose range of 23-736 nmol) producing a 20% decrease in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curves. Patients were studied on 3 separate days in a randomized, double-blind manner. On the first day a baseline PD20 value was determined. On subsequent days substance P challenge was performed after pretreatment (20 min before challenge) with either placebo or nedocromil sodium. Student's paired t-test and Wilcoxon's test were used for statistical analysis. The results of this study demonstrated that inhalation of substance P causes a dose-dependent bronchoconstriction and that the bronchoconstriction induced by substance P can be prevented by pre-treatment with nedocromil sodium.     

825.

Human interleukin 4 regulates the phenotype of lymphocytes generated during mixed lymphocyte culture and inhibits the IL-2-induced development of LAK function in normal and leukaemic cells   总被引：2，自引：0，他引：2  

B Q Jin  A F Lopez  S Gillis  C A Juttner  M A Vadas  G F Burns 《Leukemia research》1989,13(4):297-305

This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function.     

826.

Phenotypic variability in a large kindred (Family LA) with deletions in the parkin gene.     

Peter P Pramstaller  Bernhard Kis  Cordula Eskelson  Katja Hedrich  Monika Scherer  Eberhard Schwinger  Xandra O Breakefield  Patricia L Kramer  Laurie J Ozelius  Christine Klein 《Movement disorders》2002,17(2):424-426

     

827.

Percutaneous Endovascular Treatment for Stenoses and Occlusions of Infrarenal Aorta and Aortoiliac Bifurcation: Midterm Results     

B. J. d'Othe  S. Haulon  C. Mounier-Vehier  J. P. Beregi  O. Jabourek  S. Willoteaux 《European journal of vascular and endovascular surgery》2002,24(6):516-523

OBJECTIVE: evaluation and comparison of the endovascular treatment of isolated aortic and aortoiliac atherosclerotic lesions (stenoses and occlusions). METHODS: a percutaneous endovascular procedure was performed in 52 patients (38 men and 14 women) with a mean age of 52 years (range, 25-85 years). The baseline angiogram showed 35 aortic lesions (31 stenoses, 4 occlusions) and 17 aortoiliac lesions (14 stenoses, 3 occlusions). Percutaneous techniques used in this series included variable combinations of transluminal angioplasty and stenting. All stents placements were performed over-the-wire using the transfemoral route (most often bilateral approach). Clinical examination and Duplex-scan were performed at discharge, 1 month, 6 months, 12 months, and then yearly. RESULTS: technical success was 100% for aortic and aortoiliac lesions. Angiographic success rates were comparable for aortic (91%) and aortoiliac (94%) lesions. No death occurred during or early after the endovascular intervention. Duplex-scan confirmed 100% patency rate at discharge. There was no significant difference between the aortic (94%) and aortoiliac (96%) groups regarding immediate clinical improvement. Mean follow-up was 34+/-31 months (range, 0-130 months). The cumulative primary patency rate at 36 months was 85% in the aortic group and 86% in the aortoiliac group. Clinical success, defined as a symptom-free status at the end of follow-up, was also similar in both groups. CONCLUSION: endovascular treatment of isolated aortic lesions of the infra-renal aorta has favorable outcomes comparable to those of aortoiliac lesions.     

828.

Beeinflussung humaner Osteoblasten durch verschiedene Analgetika     

G. Matziolis  H. M. Rau  P. Klever  H. J. Erli  O. Paar 《Der Unfallchirurg》2002,73(4):527-531

In der Behandlung von Frakturen spielt die Analgesie eine wesentliche Rolle. Es stellt sich daher die Frage, ob in der Klinik h?ufig eingesetzte Analgetika wie Tramadol oder Diclofenac negative Wirkungen auf die Knochenbruchheilung haben.     

829.

Erythropoietin production in healthy volunteers subjected to controlled hypobaric hypoxia: further evidence against a role for adenosine   总被引：2，自引：2，他引：0  

C. H. Gleiter  T. Becker  & J. Wenzel 《British journal of clinical pharmacology》1997,44(2):203-205

Aims Objective of this study was to investigate whether adenosine modulates renal erythropoietin production.
Methods In the present study erythropoietin production was stimulated by hypobaric hypoxia by subjecting healthy volunteers to a simulated altitude of 4000  m in a low pressure chamber for 5.5  h. During exposure to hypoxia the subjects received i.v. in a randomized, single-blind, cross-over fashion the non-specific adenosine antagonist theophylline, the adenosine reuptake inhibitor dipyridamole and placebo.
Results Contrary to the working hypothesis, theophylline did not decrease and dipyridamole did not further boost erythropoietin concentrations.
Conclusions The results are in agreement with our earlier study using haemorrhage as a controlled physiological stimulus of erythropoietin production, and would question a major role for adenosine as a mediator of renal erythropoietin production.     

830.

Association of HLA type with pseudoexfoliation of the lens capsule          下载免费PDF全文

G SESHUBABU  J FITZSIMON  A MULVIHILL  S KENNEDY  A FINCH  L COLLUM    P EUSTACE 《The British journal of ophthalmology》1997,81(1):93-94

     

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Effect of nedocromil on bronchospasm induced by inhalation of substance P in asthmatic subjects

Several studies have demonstrated that neuropeptides are present in peptidergic fibres of bronchial tissue. The aim of the present study was to evaluate in vivo the effect of nedocromil sodium (2 x 2 mg) on bronchospasm induced by inhalation of substance P. Six moderate asthmatic patients, mean age 25.17 years, were studied. Airway response was measured as FEV1 and the dose of substance P (using a dose range of 23-736 nmol) producing a 20% decrease in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curves. Patients were studied on 3 separate days in a randomized, double-blind manner. On the first day a baseline PD20 value was determined. On subsequent days substance P challenge was performed after pretreatment (20 min before challenge) with either placebo or nedocromil sodium. Student's paired t-test and Wilcoxon's test were used for statistical analysis. The results of this study demonstrated that inhalation of substance P causes a dose-dependent bronchoconstriction and that the bronchoconstriction induced by substance P can be prevented by pre-treatment with nedocromil sodium.     

Human interleukin 4 regulates the phenotype of lymphocytes generated during mixed lymphocyte culture and inhibits the IL-2-induced development of LAK function in normal and leukaemic cells

This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function.     

Percutaneous Endovascular Treatment for Stenoses and Occlusions of Infrarenal Aorta and Aortoiliac Bifurcation: Midterm Results

OBJECTIVE: evaluation and comparison of the endovascular treatment of isolated aortic and aortoiliac atherosclerotic lesions (stenoses and occlusions). METHODS: a percutaneous endovascular procedure was performed in 52 patients (38 men and 14 women) with a mean age of 52 years (range, 25-85 years). The baseline angiogram showed 35 aortic lesions (31 stenoses, 4 occlusions) and 17 aortoiliac lesions (14 stenoses, 3 occlusions). Percutaneous techniques used in this series included variable combinations of transluminal angioplasty and stenting. All stents placements were performed over-the-wire using the transfemoral route (most often bilateral approach). Clinical examination and Duplex-scan were performed at discharge, 1 month, 6 months, 12 months, and then yearly. RESULTS: technical success was 100% for aortic and aortoiliac lesions. Angiographic success rates were comparable for aortic (91%) and aortoiliac (94%) lesions. No death occurred during or early after the endovascular intervention. Duplex-scan confirmed 100% patency rate at discharge. There was no significant difference between the aortic (94%) and aortoiliac (96%) groups regarding immediate clinical improvement. Mean follow-up was 34+/-31 months (range, 0-130 months). The cumulative primary patency rate at 36 months was 85% in the aortic group and 86% in the aortoiliac group. Clinical success, defined as a symptom-free status at the end of follow-up, was also similar in both groups. CONCLUSION: endovascular treatment of isolated aortic lesions of the infra-renal aorta has favorable outcomes comparable to those of aortoiliac lesions.     

Beeinflussung humaner Osteoblasten durch verschiedene Analgetika

In der Behandlung von Frakturen spielt die Analgesie eine wesentliche Rolle. Es stellt sich daher die Frage, ob in der Klinik h?ufig eingesetzte Analgetika wie Tramadol oder Diclofenac negative Wirkungen auf die Knochenbruchheilung haben.     

Erythropoietin production in healthy volunteers subjected to controlled hypobaric hypoxia: further evidence against a role for adenosine

Aims Objective of this study was to investigate whether adenosine modulates renal erythropoietin production.
Methods In the present study erythropoietin production was stimulated by hypobaric hypoxia by subjecting healthy volunteers to a simulated altitude of 4000  m in a low pressure chamber for 5.5  h. During exposure to hypoxia the subjects received i.v. in a randomized, single-blind, cross-over fashion the non-specific adenosine antagonist theophylline, the adenosine reuptake inhibitor dipyridamole and placebo.
Results Contrary to the working hypothesis, theophylline did not decrease and dipyridamole did not further boost erythropoietin concentrations.
Conclusions The results are in agreement with our earlier study using haemorrhage as a controlled physiological stimulus of erythropoietin production, and would question a major role for adenosine as a mediator of renal erythropoietin production.