Clinical, brain electric earth map, endothelin and transcranial ultrasonic Doppler findings after hyperbaric oxygen treatment for severe brain injury

Objective　To analyze the effect and mechanism of hyperbaric oxygen (HBO) treatment for severe brain injury (SBI). Methods　Fifty-five patients were divided into a treatment group of 35 patients and a control group of 20 patients. We observed the alterations of clinical, brain electric earth map (BEAM), endothelin (ET) and transcranial ultrasonic Doppler (TCD) findings before and after HBO treatment as well as outcome. Results　In the treatment group, Glasgow coma scale, BEAM and outcome improved after HBO treatment; compared with that of the control group, it showed a significant difference. After one course of treatment, treatment group ET was reduced from 91.24±12.18?ng/L to 68.88±14.37?ng/L (P<0.01); in control group, ET was reduced from 90.78±15.71?ng/L to 83.12±12.22?ng/L, with a statistically significant difference (P<0.05). TCD records of MCA mean velocity (Vm) was reduced from 64.2±4.8?cm/s to 51.6±4.2?cm/s (P<0.01), and a decrease in MCA systolic velocity (Vs) and pulse index (PI) values was statistically significant (P<0.01). Conclusion　HBO treatment can improve the clinical, BEAM and outcome of severely brain injured patients, by decreasing acute stage ET and improving the blood velocity of MCA and decreasing cerebral vascular resistance. HBO treatment can reduce cerebral vascular spasms, cerebral ischemia and hypoxia. One of the important mechanisms of HBO treatment for severe brain injury is the lowering of intracranial pressure.     

短链脂肪酸在溃疡性结肠炎病因及治疗中的作用

溃疡性结肠炎(ulcerative colitis,UC)的病因仍不是十分清楚.关于该疾病的假说主要集中在粘膜损伤的启动及持续机制上.病因学假说有短链脂肪酸(short chain fally acid,SCFA)的代谢障碍[1],细菌的化学趋向性多肽导致表皮屏障功能的丧失[2]、细菌内毒素[3]、细菌产生的硫化物[1]及免疫网络的失调和肠腔粘膜免疫活性的增强[4]等.有许多证据支持上述假说,但也有一些不尽完善之处.现就SCFA在UC病因及治疗上的研究成果作一综述.     

Continuous mannose infusion in carbohydrate-deficient glycoprotein syndrome type I

The effects on isoelectrofocusing patterns of serum glycoproteins were studied in a patient with CDG syndrome type I and phosphomannomutase deficiency during 3 weeks of continuous intravenous mannose infusion. Doses of 5. 7 g/kg/day led to stable serum mannose levels up to 2. 0 mmol/1 and were well tolerated without signs of liver or renal toxicity. While most of the pathological glycoprotein patterns, including α₁-antitrypsin, typical for CDG syndrome type I remained unchanged, mannose infusion led to a unique change of the isoelectrofocusing pattern of serum sialotransferrins with appearance of two extra bands after 3 weeks of treatment.     

The influence of obesity on survival in early,high-risk breast cancer: results from the randomized SUCCESS A trial

Introduction

Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear.

Methods

This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0–29.9), slightly obese (BMI 30.0–34.9), moderately obese (BMI 35.0–39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors.

Results

Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71–4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63–4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes.

Conclusions

Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02181101","term_id":"NCT02181101"}}NCT02181101. Registered September 2005.     

Long-term treatment of canine cyclic hematopoiesis with recombinant canine stem cell factor

Grey collie dogs have cyclic fluctuations in their blood cell counts caused by a regulatory defect of hematopoietic stem cells. To examine the role of stem cell factor (SCF) or its receptor in this disorder, we investigated the stimulatory effects of recombinant canine SCF (rc-SCF) on in vitro marrow cultures, cloned and sequenced the grey collie SCF gene, and treated three grey collies with rc-SCF, either alone or in combination with recombinant canine granulocyte colony-stimulating factor (rcG-CSF). Colony-forming unit granulocyte-macrophage formation from grey collie or normal dog marrow showed similar dose-response curves for rc-SCF. Cloning and sequencing the SCF gene for two grey collies showed no evidence of mutations in the coding region of the SCF gene. Treatment with rc-SCF (10 to 100 micrograms/kg/d) did not induce neutrophilia except at the highest dose (100 micrograms/kg/d), but daily rc-SCF abrogated the neutropenic periods in doses of 20 micrograms/kg/d or greater. Combination of rc-G-CSF (0.5 to 1.0 microgram/kg/d) with rc-SCF treatment (20 to 50 micrograms/kg/d) suggested a synergistic effect, ie, the neutrophil levels on combined therapy were higher than the sum of the levels when these two cytokines were given separately. Long-term treatment of these dogs with rc-SCF in doses of 10 to 30 micrograms/kg/d was generally well tolerated, suggesting that SCF may be useful as a therapy for some chronic hypoproliferative disorders of hematopoiesis.     

Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukemia

Using flow cytometric techniques, we determined the pretreatment distribution of DNA content in propidium iodide-stained leukemic blasts from 205 children with "standard-risk" acute lymphoblastic leukemia (ALL). Risk assignment was based on an initial WBC count less than 100 X 10(9)/L, no thymic mass, no meningeal leukemia, and lymphoblasts lacking sheep erythrocyte receptors or surface immunoglobulin. A single aneuploid leukemic line was detected in 74 cases (36.1%): 70 hyperdiploid and four hypodiploid. For hyperdiploid cases, the DNA index (DI, or ratio of the DNA content of leukemic v normal G0/G1 cells) ranged from 1.06 to 2.0 (median, 1.20). A secondary leukemic line with hyperdiploid cellular DNA content was identified in 21 cases with diploid primary lines. Children whose primary leukemic line showed a DI greater than or equal to 1.16 (n = 57) had significantly better responses to treatment than did those with either a diploid DI (n = 130; P = .002) or values in the range of 1.01 to 1.15 (n = 14; P = .001). The relative risk of failure for hyperdiploid cases with DI greater than or equal to 1.16, corresponding to greater than or equal to 53 chromosomes, was one-third that of the other two groups. Treatment responses of patients with both diploid and hyperdiploid lines were identical to those associated with single diploid lines, but significantly worse than those associated with single hyperdiploid lines with DI greater than or equal to 1.16 (P = .016). The most favorable prognostic variables selected by a Cox proportional hazards model were: DI greater than or equal to 1.16 (P = .001), white race (P = .022), WBC less than or equal to 25 X 10(9)/L (P = .032), age between 2 and 9 years (P = .075), and hemoglobin less than 7.0 g/dL (P = .094). DNA index greater than or equal to 1.16 retained its significant prognostic impact even after adjustment for other variables (P = .001). With the combination of DI greater than or equal to 1.16 and WBC less than or equal to 25 X 10(9)/L, one can identify a group of children with ALL who have a low probability of relapse when treated with current therapy. If they remain disease-free after longer follow-up, it may be advisable to treat them with less intensive, hence less toxic, chemotherapy than patients with higher WBC counts or lower DI values.     

Neutrophil migration is defective during recombinant human granulocyte- macrophage colony-stimulating factor infusion after autologous bone marrow transplantation in humans

We have previously reported that continuous intravenous (IV) administration of recombinant granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) to humans following high-dose alkylating agent chemotherapy and autologous bone marrow support (ABMS) results in myeloid bone marrow maturation, accelerated granulocyte recovery, and reduced treatment-related toxicity. However, we found that leukocyte counts declined rapidly after discontinuation of rHuGM-CSF therapy, which suggests possible growth factor effects on leukocyte margination and migration. For these reasons we studied granulocyte margination by using 111In-labeled autologous granulocytes and found similar granulocyte margination before (21.5% +/- 13.4%) and during continuous IV rHuGM-CSF infusion (23.3% +/- 9.6%). Phagocytosis of Cryptococcus neoformans and granulocyte hydrogen peroxide production was similar before and during rHuGM-CSF infusion and similar to patients treated with the same high-dose chemotherapy and ABMS but not receiving growth factor. However, migration of granulocytes to a sterile inflammatory site was markedly reduced during continuous rHuGM-CSF infusion (1.2 +/- 0.9 WBCs/cm2, 24 hr) as compared with baseline (39.6 +/- 17.7 WBCs/cm2/24 hr; P less than .0008). These findings may be of relevance when extravascular granulocytes are required for host defense.     

Comparative effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy

Two hematopoietic colony-stimulating factors, granulocyte colony- stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF), have been shown to accelerate leukocyte and neutrophil recovery after high-dose chemotherapy and autologous bone marrow (BM) support. Despite their use, a prolonged period of absolute leukopenia persists during which infections and other complications of transplantation occur. We collected large numbers of peripheral blood (PB) progenitors after CSF administration using either G-CSF or GM-CSF and tested their ability to affect hematopoietic reconstitution and resource utilization in patients undergoing high-dose chemotherapy and autologous BM support. Patients with breast cancer or melanoma undergoing high-dose chemotherapy and autologous BM support were studied in sequential nonrandomized trials. After identical high-dose chemotherapy, patients received either BM alone, with no CSF; BM with either G-CSF or GM-CSF; or BM with G-CSF or GM-CSF and G-CSF or GM-CSF primed peripheral blood progenitor cells (PBPC). Hematopoietic reconstitution, as well as resource utilization, was monitored in these patients. The use of CSF- primed PBPC led to a highly significant reduction in the duration of leukopenia with a white blood cell (WBC) count under 100 and 200 cells/mL, and neutrophil count under 100 and 200 cells/mL with both GM- and G-CSF primed PB progenitor cells, compared with the use of the CSF with BM or with historical controls using BM alone. In addition, the use of CSF-primed PBPC resulted in a significant reduction in median number of antibiotics used, days in the Bone Marrow Transplant Unit, and hospital resources used. Patients receiving G-CSF primed PBPC also experienced a reduction in the median number of days in the hospital, red blood cell (RBC) transfusions, platelet transfusions, days on antibiotics, and discounted hospital charges. Phenotypic analysis of the CSF-primed PBPC indicated the presence of cells bearing antigens associated with both early and late hematopoietic progenitor cells. The use of CSF-primed PBPC can significantly improve hematopoietic recovery after high-dose chemotherapy and autologous BM support. In addition, the use of G-CSF-primed PBPC was associated with a significant reduction in hospital resource utilization, and a reduction in hospital charges.     

白三烯拮抗剂ONO-1078对小鼠持续性局灶性脑缺血的作用

目的在小鼠模型研究白三烯拮抗剂{4-氧-8-[对-(4-苯丁氧基)苯甲酰氨基]-2-(5-四唑基)-4H-1-苯并吡喃半水合物(ONO-1078)}对脑缺血的保护作用.方法以大脑中动脉阻塞法诱导持续性局灶性脑缺血.在脑缺血前30min和缺血后60min腹腔注射ONO-1078、尼莫地平或生理盐水(对照).脑缺血24h后,观察神经症状,并测定脑湿重和脑梗死体积.结果ONO-1078(0.01,0.03,0.1mgkg-1)和尼莫地平(0.2 mg*kg-1)减少脑梗死体积;ONO-1078(0.1 mg kg-1)减轻脑湿重,尼莫地平无此作用;ONO-1078和尼莫地平对神经症状无明显作用.结论ONO-1078对持续性局灶性脑缺血有保护作用,提示白三烯拮抗剂可作为急性脑缺血的一种新治疗药.