p < 0.05). On postoperative
days 3 and 7 the values were 7.2 (5.3–8.2) and 7.5 (5.4–9.4) mmol/L,
respectively, in the erythropoietin group compared to 6.7 (5.2–7.8)
and 6.9 (5.1–8.6) mmol/L in the placebo group (p <
0.01). At discharge the hemoglobin concentration was 7.8 (5.9–8.8)
mmol/L in the erythropoietin group and 7.2 (5.4–8.6) mmol/L in the
placebo group (p < 0.002). The blood loss during
operation was similar in the two groups. In the erythropoietin group
the median value was 280 ml (range 25–2000 ml), with the lower and
upper quartiles 150 and 500 ml, respectively. In the placebo group the
blood loss was median 300 ml (range 50–1800 ml), with the lower and
upper quartiles 200 and 750 ml, respectively. The number of blood
transfusions given was significantly lower in the erythropoietin group,
with a mean of 0.3 (range 0–6) units compared to 1.6 (0–9) units in
the control group (p < 0.05). In conclusion, the
hemoglobin concentration at the time of surgery and during the week
following surgery was significantly higher in the group of patients
receiving r-HuEPO perioperatively compared to the placebo group
together with a significant lower use of blood transfusions in the
r-HuEPO group. However, the clinical implications of these findings has
yet to be proven.RID=" ID=" <E5>Correspondence to:</E5> N. Qvist, M.D., D.Sci. 相似文献
For the first time the human intestinal effective permeability, estimated from the luminal disappearance and intestinal metabolism of phytochemicals, sulforaphane and quercetin-3,4'-glucoside, as well as the simultaneous changes in gene expression in vivo in enterocytes, has been studied in the human jejunum in vivo (Loc-I-Gut). Both compounds as components of an onion and broccoli extract could readily permeate the enterocytes in the perfused jejunal segment. At the physiologically relevant, dietary concentration tested, the average effective jejunal permeability (Peff) and percentage absorbed (+/- S.D.) were 18.7 +/- 12.6 x 10-4 cm/s and 74 +/- 29% for sulforaphane and 8.9 +/- 7.1 x 10-4 cm/s and 60 +/- 31% for quercetin-3,4'-diglucoside, respectively. Furthermore, a proportion of each compound was conjugated and excreted back into the lumen as sulforaphane-glutathione and quercetin-3'-glucuronide. The capacity of the isolated segment to deconjugate quercetin from quercetin-3,4'-diglucoside during the perfusion was much higher than the beta-glucosidase activity of the preperfusion jejunal contents, indicating that the majority (79-100%) of the beta-glucosidase capacity derives from the enterocytes in situ. Simultaneously, we determined short-term changes in gene expression in exfoliated enterocytes, which showed 2.0 +/- 0.4-fold induction of glutathione transferase A1 (GSTA1) mRNA (p < 0.002) and 2.4 +/- 1.2-fold induction of UDP-glucuronosyl transferase 1A1 (UGT1A1) mRNA (p < 0.02). The changes in gene expression were also seen in differentiated Caco-2 cells, where sulforaphane was responsible for induction of GSTA1 and quercetin for induction of UGT1A1. These results show that food components have the potential to modify drug metabolism in the human enterocyte in vivo very rapidly. 相似文献
PURPOSE: To assess oregovomab as consolidation treatment of advanced ovarian cancer and refine the immunotherapeutic strategy for subsequent study. PATIENTS AND METHODS: Patients with stage III/IV ovarian cancer who had a complete clinical response to primary treatment were randomly assigned to oregovomab or placebo administered at weeks 0, 4, and 8, and every 12 weeks up to 2 years or until recurrence. The primary end-point was time to relapse (TTR). RESULTS: One hundred forty-five patients were treated with oregovomab (n = 73) or placebo (n = 72). For the population overall, median TTR was not different between treatments at 13.3 months for oregovomab and 10.3 months for placebo (P =.71). Immune responses were induced in most actively treated patients. This was associated with prolonged TTR. Quality of life was not adversely impacted by treatment. Adverse events were reported with similar frequency in oregovomab and placebo groups, indicating a benign safety profile. A long-term survival follow-up is ongoing. Cox analysis of relapse data identified significant factors: performance status, CA-125 before third cycle, and baseline CA-125. Further evaluation identified a subpopulation with favorable prognostic indicators designated as the successful front-line therapy (SFLT) population. For the SFLT population, TTR was 24.0 months in the oregovomab group compared with 10.8 months for placebo (unadjusted hazard ratio of 0.543 [95% CI, 0.287 to 1.025]), a hypothesis-generating observation. CONCLUSION: Consolidation therapy with oregovomab did not significantly improve TTR overall. A set of confirmatory phase III studies has been initiated to determine whether the SFLT population derives benefit from oregovomab treatment. 相似文献
Background and purpose: Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer, but its impact on the therapeutic index is unknown. This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment.
Patients and methods: Thirty-nine patients from two centers irradiated for head and neck cancer received i.v.-infusions of amifostine prior to each radiation fraction. In a phase III study, two daily amifostine doses, 200 mg/m2 (n=21) and 340 mg/m2 (n=18), were compared for protection against radiation induced toxicity. Total radiation dose was 60–70 Gy (2 Gy per fraction), nine patients received concurrent chemotherapy with cisplatin/5-FU. amifostine was usually discontinued after >1 episode of serious toxicity during subsequent treatment sessions.
Results: In 16/39 patients (41%) amifostine was discontinued due to severe adverse effects, which led to discontinuation of the phase III study. In four of 16 patients radiotherapy was delayed due to amifostine related adverse effects for 1–3 days. Discontinuation occurred more often in patients receiving chemotherapy. The results led to a literature review for amifostine treatment during radiotherapy in head and neck cancer patients. Regarding our series and published series using an amifostine schedule comparable to ours, total discontinuation rate was 27% (57/214). Discontinuation was significantly influenced by chemotherapy (P=0.007), but not by amifostine dose (P=0.156).
Conclusion: Daily i.v. administration of amifostine during radiotherapy in head and neck cancer is associated with a high rate of serious adverse effects leading to discontinuation of amifostine treatment and sometimes delay of radiotherapy. 相似文献
A noninvasive system designed for patient tracking during image-guided intranasal sinus surgery is described. It is based on optical digitizing with a custom-made registration and reference system, locatable surgical instruments, and a self-localizing operating microscope. Experimental and clinical results reveal a high degree of accuracy for the system. A mean spatial error of 0.82 ± 0.31 mm was determined for repositioning of the reference system in a plastic model of the skull. For the positioning of the microscope, a mean error of 2.3 ± 0.83 mm was calculated. Measurements of repositioning accuracy in 24 patients who received surgery for various sinus diseases had a mean spatial error of 1.56 ± 0.76 mm. The 95% error interval for locating intranasal structures using the surgical instrument was 2.05 mm, and it was 4.92 mm using the microscope. These results suggest that the use of our noninvasive registration and reference system may be effective, accurate, and useful for noninvasive tracking of patient movements in computer-assisted intranasal surgery. 相似文献
Previous work from our laboratory demonstrated aneuploidy for several chromosomes by interphase fluorescence in situ hybridization (FISH) in a high proportion of breast cancer specimens. In the literature, only limited data are available concerning chromosome 8 anomalies in breast cancer. To determine chromosome 8 ploidy status in primary and metastatic specimens from 81 breast cancer patients, FISH analysis with a DNA probe recognizing chromosome 8 centromeres was performed. In all primary tumor specimens (n=30), significant proportions of cells were aneuploid exhibiting gain of chromosome 8 copy numbers; in 75% of effusion specimens previously classified as malignant by cytology and/or FISH for various chromosomes (n=40), cell populations aneuploid for chromosome 8 were detected; effusions previously classified non-malignant (n=11) were diploid in 10 cases, whereas one specimen contained rare hyperdiploid cells. Among these cells complex chromosomal aneuploidy could be demonstrated by two-color FISH, suggesting malignancy. Trisomic and tetrasomic clones were predominant in the majority of samples, but a marked intratumor cytogenetic heterogeneity was observed in most cases. Primary tumors and corresponding positive axillary lymph nodes revealed similar distributions of chromosome 8 copy numbers, analogous to previous findings with other chromosomes. This implies that, by using suitable FISH probes after examination of the respective primary tumor, an efficient search for (micro)metastasis might be feasible. 相似文献