Reevaluation of procarbazine for the treatment of recurrent malignant central nervous system tumors

Ninety-nine patients with primary recurrent malignant tumors of the central nervous system were treated with procarbazine as a single agent. Procarbazine was not given as a specified protocol, but for patients who were ineligible or refused other protocols. All patients had been treated previously with radiotherapy and 96 patients had also received previous chemotherapy. Twenty-five patients were treated at the first progression of their tumor, 47 were treated at the second progression, and 27 were treated at the third progression of their tumor. For the aggregate, the response plus stabilization rate was 27% for glioblastoma multiforme with median time to tumor progression of 30 weeks, and 28% for other anaplastic gliomas with a median time to tumor progression of 49 weeks. With respect to the percent of patients who responded or stabilized to treatment, these results are inferior to those reported previously for patients treated with procarbazine at recurrence. With respect to duration of response and stabilization, the data are comparable.     

High concentrations of antibiotic obtained for a short time excel more long-standing lower levels in the therapy of gonorrhoea. Implications of an in vitro model

During recent decades there has been a controversial discussion if comparable plasma level profiles which are rather constant or those which show a high peak are more efficient for the cure of gonorrhoea. So far, investigations in this field were not based on the Grasso apparatus. Although the findings with cefotiam and ceftizoxime do not allow to formulate a general hypothesis without any restriction, it can be stated that on the basis of an identical area under the antibiotic level time curve, 'peak concentration' profiles are more favourable.     

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     

997.

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.     

998.

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.     

999.

Shift work. Flexible friend     

P Shade 《Nursing times》1988,84(44):32-34

     

1000.

Non-invasive proportional assist and pressure support ventilation in patients with cystic fibrosis and chronic respiratory failure   总被引：12，自引：2，他引：10       下载免费PDF全文

A Serra  G Polese  C Braggion    A Rossi 《Thorax》2002,57(1):50-54

BACKGROUND: Patients with advanced cystic fibrosis can benefit from non-invasive positive pressure ventilation (NPPV) for the treatment of acute decompensation as well as for the management of chronic respiratory failure. This study was undertaken to compare the physiological effects of non-invasive proportional assist ventilation (PAV) and pressure support ventilation (PSV) on ventilatory pattern, transcutaneous blood gas tensions, and diaphragmatic effort in stable patients with cystic fibrosis and chronic CO2 retention. METHODS: In 12 patients two periods of spontaneous breathing were followed randomly by PSV (12 (3) cm H2O) and PAV (flow assist 4.9 (1.3) cm H2O/l.s, volume assist 18.9 (5.1) cm H2O/l) set for the patient's comfort and administered for 40 minutes with 2 cm H2O continuous positive airway pressure. Ventilatory pattern, transcutaneous blood gas tensions, and surface diaphragmatic electromyography were measured in the last 10 minutes of each application. RESULTS: On average, both PSV and PAV improved ventilation (+30%), tidal volume (+30%), and transcutaneous CO2 (-7%) while reducing diaphragmatic activity (-30% with PSV, -20% with PAV). Mean inspiratory airway pressure was lower during PAV than during PSV (9.7 (1.9) and 12.9 (2.7) cm H2O, respectively; p<0.05). The mean coefficient of variation of tidal volume was about 20% (range 11-39%) during spontaneous breathing and did not change with either PAV or PSV. CONCLUSIONS: These results show that short term administration of nasal PAV and PSV to patients with stable cystic fibrosis with chronic respiratory insufficiency is well tolerated, improves ventilation and blood gas tensions, and unloads the diaphragm.     

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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.     

Non-invasive proportional assist and pressure support ventilation in patients with cystic fibrosis and chronic respiratory failure

BACKGROUND: Patients with advanced cystic fibrosis can benefit from non-invasive positive pressure ventilation (NPPV) for the treatment of acute decompensation as well as for the management of chronic respiratory failure. This study was undertaken to compare the physiological effects of non-invasive proportional assist ventilation (PAV) and pressure support ventilation (PSV) on ventilatory pattern, transcutaneous blood gas tensions, and diaphragmatic effort in stable patients with cystic fibrosis and chronic CO2 retention. METHODS: In 12 patients two periods of spontaneous breathing were followed randomly by PSV (12 (3) cm H2O) and PAV (flow assist 4.9 (1.3) cm H2O/l.s, volume assist 18.9 (5.1) cm H2O/l) set for the patient's comfort and administered for 40 minutes with 2 cm H2O continuous positive airway pressure. Ventilatory pattern, transcutaneous blood gas tensions, and surface diaphragmatic electromyography were measured in the last 10 minutes of each application. RESULTS: On average, both PSV and PAV improved ventilation (+30%), tidal volume (+30%), and transcutaneous CO2 (-7%) while reducing diaphragmatic activity (-30% with PSV, -20% with PAV). Mean inspiratory airway pressure was lower during PAV than during PSV (9.7 (1.9) and 12.9 (2.7) cm H2O, respectively; p<0.05). The mean coefficient of variation of tidal volume was about 20% (range 11-39%) during spontaneous breathing and did not change with either PAV or PSV. CONCLUSIONS: These results show that short term administration of nasal PAV and PSV to patients with stable cystic fibrosis with chronic respiratory insufficiency is well tolerated, improves ventilation and blood gas tensions, and unloads the diaphragm.