Controlled multicentre study of the influence of subcutaneous recombinant human erythropoietin on anaemia and transfusion dependency in patients with ovarian carcinoma treated with platinum-based chemotherapy

This randomised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin (rhEPO) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy. The patients were randomly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously, three times a week, or open control. Patients also received up to 6 cycles of carboplatin or cisplatin, alone or in combination with other cytotoxic agents. Intention-to-treat analysis showed that 39.4% of patients in the control group received at least one blood transfusion, compared with 9.2% of patients treated with rhEPO. Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels <10 g/dl (P<0.001 and <0.05, respectively). A haemoglobin decrease <1 g/dl during the first chemotherapy cycle, as well as a low baseline serum erythropoietin concentration, predicted a low transfusion need in rhEPO-treated patients but not in controls. During the study, 103 patients suffered at least one adverse event, but no serious, and only nine non-serious adverse events were considered possibly related to rhEPO therapy. These results indicate that treatment with rhEPO prevents anaemia, it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy, and it is well tolerated. A starting dose of 150 U/kg of rhEPO, three times a week, may be recommended.     

Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution

The association between glutathione S-transferase (GST) activity as measured by 1-chloro-2,4-dinitrobenzene (CDNB) conjugation and genotype at exon 5 and exon 6 of the human GSTP1 gene was investigated in normal lung tissue obtained from 34 surgical patients. These samples were genotyped for previously identified polymorphisms in exon 5 (Ile105Val) and exon 6 (Ala114Val) by PCR-RFLP and direct sequencing. GST enzyme activity was significantly lower among individuals with the 105 Val allele. Homozygous Ile/Ile samples (n = 18) had a mean cytosolic CDNB conjugating activity of 74.9 +/- 3.8 nmol/mg per min; heterozygotes (n = 13) had a mean specific activity of 62.1 +/- 4.2 nmol/mg per min and homozygous Val/Val (n = 3) had a mean specific activity of 52.5 +/- 4.5 nmol/mg per min. The CDNB conjugating activity measured for the Ile/Ile genotype group was significantly different from that observed in the Ile/Val group (P = 0.03), and from Ile/Val and Val/Val genotypes combined (P = 0.009). Mean GST activity values were consistently lower in individuals with genotypes containing the 105 valine allele, regardless of smoking exposure. Genotypes at codon 114 were also assessed but the mean GST activity was not significantly lower in individuals with the 114 valine allele. A new haplotype, present in two samples who were homozygous 105Ile and had a 114Val, was identified and proposed as GSTP1*D. Frequencies of the exon 5 and exon 6 polymorphisms were determined in samples obtained from European-Americans, African- Americans and Taiwanese. The differences observed were highly significant suggesting the possibility of GSTP1 genotype-associated, ethnic differences in cancer susceptibility and chemotherapeutic response.      

Surgical treatment of necrotizing enterocolitis: when? how?

In 10 years (1981–1990) 28 out of 54 neonates (51.8%) with definite necrotizing enterocolitis (NEC) underwent surgery. Operation was performed at 13.5 ± 8.8 (range 3–38) days of life, after 1.7 ± 1.5 (range 1–6) days from the onset of symptoms. Aiming to perform laparotomy before the occurrence of perforation, surgery was liberally indicated in stage Ilia, according to Walsh-Kliegman. Explorative laparotomy (+peritoneal drainage in 2 cases) was performed in 4 patients with massive intestinal necrosis: all died within 3 days of surgery. In one neonate, only pneumatosis was present and resection was not considered mandatory. Intestinal resection and enterostomy was performed in 17 neonates, 5 of them with perforation; three developed an intestinal stenosis. Enterostomy was closed after 116.2 ± 61.8 days (range 26–193); 11 patients (64.7%) are long-term survivors. Intestinal resection and primary anastomosis was performed in 6 babies, 3 of them with perforation. Postoperatively, 2 dehiscences and 1 stenosis were recorded, but all children survived. In our opinion, resection followed by primary anastomosis seems to be the most satisfactory surgical option.     

激光特征与其诱导骨肉瘤多药耐药细胞凋亡的生物学效应

目的:探讨激光诱导骨肉瘤多药耐药细胞凋亡的分子机制。资料来源:应用计算机检索Pubmed1996/2006的相关文章,检索词为“laser,osteosarcoma,apoptosis”并限定语种为“English”,应用计算机检索“中国期刊网CNKI数字图书馆”1996/2006的中文文章,检索词为“激光,骨肉瘤,凋亡”。资料选择:对资料进行初审,查找全文的文献。纳入标准为:与激光诱导肿瘤凋亡的机制有关。排除标准为较陈旧和重复研究的文章。资料提炼:共收集到72篇文章,其中31篇文献符合纳入标准,其中关于氧自由基方面的文章5篇,关于细胞内钙离子浓度的文章5篇,关于蛋白激酶C的文章6篇,关于Bcl-2的文章5篇,关于P53的文章8篇。资料综合:激光诱导肿瘤细胞凋亡的机制主要包括以活性氧簇为主的自由基、细胞内Ca2 浓度、蛋白激酶C家族、Bcl-2家族、p53基因等。目前的报道多侧重于低强度激光对正常细胞的促增殖作用,而对肿瘤细胞,特别是多药耐药骨肉瘤细胞及其动物模型生物效应的研究很少,推测也可能与以上机制有关。结论:激光诱导骨肉瘤凋亡的分子机制还不清楚,可能与细胞内活性氧自由基、钙离子浓度、蛋白激酶C、bcl-2和p53基因等相关。     

Handwriting,visuomotor integration,and neurological condition at school age

Aim The study investigated the relationships between handwriting, visuomotor integration, and neurological condition. We paid particular attention to the presence of minor neurological dysfunction (MND). Method Participants were 200 children (131 males, 69 females; age range 8–13y) of whom 118 received mainstream education (mean age 10y 5mo, SD 1y 4mo) and 82 special education (mean age 10y 8mo, SD 1y 2mo). Each child had four assessments: a neurological examination, which paid attention to the type and severity of MND, a test to measure motor performance, a handwriting test, and the Developmental Test of Visual Motor Integration. Results Dysgraphic handwriting and slow writing speed were closely related to the severity of neurological dysfunction (both p<0.001); impaired visuomotor integration was related to the presence of MND (p<0.001) but somewhat less to its severity. Impaired handwriting and visuomotor integration were strongly related to two specific dysfunctions: fine manipulative disability and coordination problems (both p<0.001). Impaired visuomotor integration was weakly related to dysfunctional muscle tone regulation (p=0.009) and sensory dysfunction (p=0.042). Interpretation Poor handwriting and impaired visuomotor integration are related to MND, but in a differential way. Poor handwriting is related to the severity of neurological dysfunction and to dysfunctions of complex supraspinal circuitries. Impaired visuomotor integration is associated with the presence of any of the most common types of MND.