碱性成纤维细胞生长因子对胎鼠宫内窘迫脑损害的疗效观察

目的探讨母鼠应用碱性成纤维细胞生长因子（ｂＦＧＦ）是否对胎鼠宫内窘迫脑损害有保护作用。方法将５３只胎龄为２０天的ＳＤ大鼠胎鼠随机分为五组，即正常对照组（Ｃ组）１１只，窘迫对照组（Ｅ组）１０只，ｂＦＧＦ治疗组Ⅰ（Ｄ１组）１０只，ｂＦＧＦ治疗Ⅱ组（Ｄ２组）１０只，ｂＦＧＦ治疗Ⅲ组（Ｄ３组）１２只。在不同时间内静脉注射ｂＦＧＦ，监测静脉注射ｂＦＧＦ后胎鼠脑细胞内外钙、钠、钾含量的变化。结果在钳夹血管前２０分钟静脉注射ｂＦＧＦ后胎鼠脑细胞胞游离钙离子浓度为４７５±９１ｎｍｏｌ／Ｌ；再灌注同时静脉注射ｂＦＧＦ后游离钙离子浓度为４７４±４９ｎｍｏｌ／Ｌ。表明ｂＦＧＦ干预组均明显高于正常对照组（３１５±８７ｎｍｏｌ／Ｌ）（Ｐ＜００１），但亦均低于窘迫对照组（５５２±９４ｎｍｏｌ／Ｌ）（Ｐ＜００５）；同时这两组的脑组织总钙、总钠及总钾含量亦有不同程度的下降。结论无论是在窘迫前还是在缺血再灌注同时静脉注射ｂＦＧＦ，ｂＦＧＦ均可减轻宫内窘迫胎鼠脑细胞钙超载，减轻脑水肿，保护缺氧脑细胞；提示对产妇或窒息新生儿应用ｂＦＧＦ可能有助于减轻窒息新生儿脑损伤     

Ureaplasma urealyticum, erythromycin and respiratory morbidity in high-risk preterm neonates

We investigated colonization with Ureaplasma urealyticum (Uu) in infants <30 weeks gestation and assessed the relationship to other risk factors influencing respiratory morbidity, plus the effect of treatment with erythromycin. Ventilated preterm infants [ n = 155; median GA 26 (23–29) weeks] were cultured for Uu in endotracheal aspirate and nasopharynx. Colonized infants were randomly assigned to treatment with erythromycin 40mg/kg/d, intravenously or orally. The rate of colonization was 29/155 (19%) and the Uu-colonized infants had lower mean gestational ages than the culture-negative infants (25 vs 26 weeks). For the colonized infants PROM (48% vs12%), chorioamnionitis in the mother (46% vs 17%) and vaginal delivery (71% vs 29%) were more common. More colonized infants needed supplemental oxygen at 36 weeks'postconceptual age ( p < 0:05). Erythromycin treatment was effective in reducing colonization with negative control cultures in 12/14 (86%) of treated infants. No significant differences were found between the colonized treated infants ( n = 14) and those not treated ( n = 14) in time with supplemental oxygen. Oxygen requirement at 36 weeks was related to lower gestational age, late appearance of PDA, late onset sepsis and signs of chorioamnionitis in the mother. We conclude that the Uu colonization is related to increasing immaturity, the presence of prolonged rupture of membranes, signs of chorioamnionitis and vaginal delivery. Treatment with erythromycin reduced colonization but did not significantly alter length of time with supplemental oxygen.     

Role of sialoglycan structures for the function of the epidermal growth factor receptor and the in vitro proliferation of head and neck cancer

Squamous cell carcinomas of the head and neck have been found to show a high expression of the receptor for epidermal growth factor (EGF). This overexpression of the receptor has been associated with malignant transformation of cells, although there is still debate as to what extent this receptor takes part in the proliferation of malignant cells and which function it fulfills. The factors which determine receptor-ligand interaction are also not clearly defined. That the extracellular domain of the EGF receptor carries carbohydrate or sialoglycan structures might be important for function of the receptor. Since tumor specific enzymes can possibly alter such structures, it was the aim of our study to investigate the role of these structures on the EGF receptor during the proliferation of head and neck carcinomas. We used the human laryngeal squamous carcinoma cell line HLaC 79 and altered, for the first time, specific glycan structures with sialidase α-2,3 and α-2,6, causing desialylation. Changes were also produced by endo-β-galactosidase and sialyltransferase. Findings were monitored by labeling with bromo-deoxyuridine. To determine receptor affinity, ¹²⁵I-labeled EGF was employed. Results showed that both cell proliferation and receptor affinity depended on the level of sialylation of the receptor carbohydrate side chains. Desialylation led to a statistically significant reduction of tumor cell proliferation to 65 ± 33% (P < 0.01), while receptor affinity decreased to 70 ± 26% (P < 0.01).The importance of EGF receptor for the proliferation of malignant cells seems to depend on the level of sialylation of glycan structures on receptor protein. A release of enzymes by tumor cells may then produce auto-control of tumor proliferation on its own. Received: 5 November 1997 / Accepted: 21 April 1998     

Effects of Pediatric Chronic Physical Disorders on Child and Family Adjustment

Research conducted primarily over the past 5–8 years on the psychosocial effects of pediatric chronic physical disorders on children and their families is reviewed. A large body of studies show that both children and their mothers, as groups, are at increased risk for psychosocial adjustment problems compared to peers, but that there is considerable individual variation in outcome. Since the last review on this topic (Eiser, 1990a), many studies have been conducted to identify risk and resistance factors associated with differences in adjustment among these children and their mothers. Improvements are noted in the theoretical basis for this work, programmatic nature of some of the research, and efforts at producing clinically relevant information. Evaluations of interventions, however, are lagging. Critical issues and future directions regarding developmental approaches, theory, method, measurement and intervention are discussed.     

Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma

Purpose: A randomized study was undertaken to assess the role of brachytherapy as a boost to external beam radiation therapy in the initial management of patients with malignant astrocytomas.

Methods and Materials: Inclusion criteria included the following: biopsy-proven supratentorial malignant astrocytoma of brain ≤6 cm in size, not crossing midline or involving corpus callosum, age 18–70, Karnofsky Performance Status (KPS) ≥70. Patients were randomized to external radiation therapy only delivering 50 Gray (Gy) in 25 fractions over 5 weeks or external radiation therapy plus a temporary stereotactic iodine-125 implants delivering a minimum peripheral tumor dose of 60 Gy. Patients were stratified to age ≤50 or >50, and KPS ≥90 or ≤80.

Results: There were 140 patients randomized between 1986 and 1996, 71 to the implant arm and 69 to external irradiation only. Pathologically 125 patients had necrosis noted in their tumor specimen. Factors associated with improved survival in univariate analysis were age ≤50, KPS ≥90, chemotherapy at recurrence, and reoperation at the original tumor site. The Cox proportional hazards model revealed the following significant factors: treatment at recurrence (chemotherapy or reoperation) with a relative risk (RR) of 0.6 (p = 0.004) and KPS ≥90 with a RR 0.6 (p = 0.007). Randomization to the implant arm was associated with a RR of 0.7 (p = 0.07). Median survival for patients randomized to brachytherapy or not were 13.8 vs. 13.2 months, respectively, p = 0.49.

Conclusions: We conclude that stereotactic radiation implants have not demonstrated a statistically significant improvement in survival in the initial management of patients with malignant astrocytoma.     

Outcome of combination chemotherapy in extensive stage small-cell lung cancer: Any treatment related progress?

During the past two decades many different treatment regimens of combination chemotherapy have been applied in extensive stage small-cell lung cancer (SCLC). This study was carried out to identify whether these modifications have resulted in an improved overall survival for extensive stage during the past two decades. In total, 1111 patients with extensive stage SCLC were included in six consecutive randomised trials in our setting from 1973 until 1992. Of these, 526 patients treated in the early period (1973–1981) were compared with 585 patients treated in the late period (1981–1992) with respect to pretreatment prognostic factors, staging, treatment and outcome. No change in the distribution of prognostic factors was detected and the frequency of patients with extensive stage was equal in the two periods, and no difference in overall response rates and survival was observed (P=0.49). Median survival in the two periods was 208 days and 215 days, respectively. No stage migration or treatment-related improved outcome was observed in extensive disease. We suggest restricting aggressive treatment to patients with favorable prognosis and long-term survival as a realistic aim.     

Influence of intratumoral basic fibroblast growth factor concentration on survival in ovarian cancer patients

Since basic fibroblast growth factor (bFGF) is considered as a potent mitogen that stimulates the growth of ovarian cancer cells, we evaluated the role of bFGF as a prognostic marker in patients with epithelial ovarian cancer. bFGF was quantified from the tumor cytoplasm of 76 patients with FIGO stage I–III ovarian cancer by a human FGF basic immunoassay (R&D Systems). After a mean follow-up period of 42 months, 50 patients were found to be free of tumor while 26 patients had died of the disease. The median bFGF concentration was 352.9 pg/mg (range 27.4–26 600 pg/mg). After dichotomization cytoplasmic expression of bFGF was found to be low in 44 tumors (≤500 pg/mg) and high in 32 tumors (>500 pg/mg). The probability of overall survival was 38.8 and 58.5% in the low bFGF and high bFGF groups, respectively (log-rank P=0.0066). In multivariate analysis, residual tumor after initial surgery and bFGF, but not histologic grade or stage of the disease, independently influenced the overall survival probability. Furthermore, tumors with high cytoplasmic expression of bFGF revealed a much greater stromal content. Therefore, we hypothesize that bFGF may induce a fibroblastic response which causes tumors with a high bFGF to be less aggressive than those with less stromal tissue.     

A prospective study of the significance of gene and chromosome alterations as prognostic indicators of breast cancer patients with lymph node metastases

In 150 surgically resected primary breast carcinomas that had axillary lymph-node metastases, we examined the incidence of loss of heterozygosity on chromosomes 16p, 16q, 17p, 17q, and 18q, point mutation of the p53 tumor-suppressor gene, nuclear immunoreaction of p53 protein, and amplifications of the c-erbB-2 and int-2 oncogenes by Southern blotting, single-strand conformation polymorphism analysis, and immunohistochemistry. We analyzed the association of these factors and conventional prognostic parameters with outcome of the patients, using Cox's univariate and multivariate analyses. The univariate analysis revealed that nuclear p53 immunoreaction, p53 mutation, and c-erbB-2 amplification as well as the number of metastatic lymph nodes, histological grade, and hormone-receptor statuses were significant prognostic indicators for both recurrence and cancer death. p53 immunoreaction was correlated more strongly with a poor prognosis than p53 mutations. The combination of p53 and c-erbB-2 effectively identified the high-risk patient group, and even among Grade 3 cases the subgroup with these alterations tended to have poorer clinical outcomes. The multivariate analysis including p53, c-erbB-2, and conventional factors. Lymph node status, grade, and p53 had independent impacts on the survival of patients. Under identical adjuvant systemic therapies, prognoses differed between the patient groups with and without alterations of p53 or c-erbB-2. Appropriate combinations of conventional factors with nuclear p53 immunoreaction and c-erbB-2 amplification would help to identify highly aggressive node-positive breast carcinomas and would aid stratification of patient groups in randomized clinical trials of adjuvant systemic therapies.     

A novel cancer vaccine composed of human-recombinant epidermal growth factor linked to a carrier protein: Report of a pilot clinical trial

Background: There is evidence of a relationship between epidermal growth factor (EGF) and tumor cell proliferation, such as the overexpression of EGF receptor (EGF-R) in different human tumors, which makes this system an interesting target for cancer treatment. Up to now, passive immunotherapy with monoclonal antibodies against the EGF-R has been assayed in clinics. Our approach consists of active immunotherapy with human EGF (hu-EGF). We conducted a pilot clinical trial to define the safety, toxicity and immunogenicity of vaccination with hu-EGF coupled to a carrier protein.Patients and methods: Ten patients with histologically-proven malignant carcinomas (colon, lung, stomach and prostate) in advanced clinical stages were enrolled. Patients were immunized twice (on days 0 and 15) with hu-EGF linked to either tetanic toxoid (TT, five patients) or P64k Neisseria Meningitidis recombinant protein (P64k, five patients), intradermically, using aluminium hydroxyde as adjuvant.Results: In both groups 60% of patients developed anti-EGF antibody titers without evidence of toxicity. Secondary reactions were very mild, limited to erythema and itching at the site of injection, which disappeared without medication.Conclusions: We conclude that the proposed vaccination with hu-EGF was well tolerated and that antibody titers against self EGF were developed. The results of this trial may be useful in the design of new clinical trials with higher dose immunization protocols and using more effective adjuvants.