复苏因子促进休眠结核杆菌复苏作用的研究

目的研究复苏因子蛋白对休眠结核杆菌的复苏作用，探索对休眠结核杆菌的最佳复苏方案。方法应用含不同浓度复苏因子蛋白的7H9液体培养基培养休眠结核杆菌H37Rv，分别在第6天、第11天、第16天、第30天检测培养物的OD值、并取10μL培养液涂于7H11平板培养、抗酸染色。结果低浓度组合有最佳复苏效果，高浓度复苏因子组合抑制体眠结核菌复苏。低浓度复苏因子A和高、低浓度的复苏因子B、C、E均有不同程度的复苏促进作用，复苏因子D和高浓度的复苏因子A均无复苏作用。重复试验结果相同。结论结核杆菌复苏因子蛋白对结核杆菌有复苏促进作用。     

A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-alpha monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10-50+ weeks). There was no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.     

Bone marrow involvement in small cell lung cancer: Prognostic significance and correlation with hematological and biochemical parameters

The more metastatic sites and bone marrow metastasis in small cell lung cancer (SCLC), the worse the prognosis. Diagnosing the bone marrow invasion at the beginning of the therapy is important for determining of the prognosis and planning the treatment. Abnormalities of some blood parameters may help to estimate the extent of bone marrow invasion by cancer cells. In this retrospective review, the changes in routine laboratory tests that may indicate bone marrow invasion, the predictive values of these tests, and the prognostic importance of bone marrow invasion were evaluated in SCLC patients who were being followed up according to a protocol. One hundred and forty‐four patients with SCLC were enrolled in this study. Retrospectively, it was evaluated that 25 (17.4%) of the patients had bone marrow metastasis. According to univariate analysis, there was a significant difference between hemoglobin, white blood cell count, platelet count, lactate dehydrogenase, alkaline phosphatase and uric acid of the patients with and without bone marrow involvement. Among the biochemical parameters, the elevated LDH and AP had the highest sensitivity and specificity as indicators of bone marrow invasion (0.80–0.82 and 0.84–0.78, respectively). The median overall survival of extensive‐stage disease with and without bone marrow metastasis were 4.0 ± 1.0 months (95% CI 2.2–5.7) and 7.0 ± 1.2 months (95% CI 4.7–9.3), respectively (P = 0.03). Bone marrow metastasis was found to be an indicator of a bad prognosis. Bone marrow biopsy, that is an invasive procedure, can be performed on selected patients who have changes of routine laboratory tests suggesting bone marrow invasion.     

Molecular analysis of PKU in Ireland

Classical phenylketonuria (PKU: McKusick No. 261600) is caused by mutations occurring at the phenylalanine hydroxylase (PAH) locus on chromosome 12 and has a prevalence in Ireland of 1 in 4500. We examined 304 independent alleles from 350 patients for the presence of six mutations and have characterized VNTR alleles within the minisatellite region 3' to the PAH gene in patients carrying the most prevalent mutation. R408W was the most common mutation found, with a relative frequency of 42%. All other mutations had relative frequencies of <10%. VNTR analysis showed that the R408W mutation is associated with the VNTR-8 allele in the Irish population, indicating that R408W is associated with RFLP haplotype 1. This differs from that reported from eastern Europe where R408W is associated with RFLP haplotype 2/VNTR-3; an observation which has led several groups to propose a Balto-Slavic origin for this mutation. These results support the hypothesis of a second, independent founding event for the R408W mutation on an RFLP haplotype 1 VNTR-8 chromsome background in the Irish/Celtic population.     

Neuroimaging findings in glutaric aciduria type 1

Objective To review the imaging features of glutaric aciduria type 1 (GA-1) in a group of 20 patients, the largest published series to date. To document the findings not previously reported and compare our findings with the imaging characteristics of GA-1 previously reported in the literature.Materials and methods For 14 patients the original scans were examined and in the remaining 6, where the imaging was unavailable, the radiology reports were consulted. Nine patients had serial cranial US examinations, 13 had 18 CT scans performed and 14 patients had 39 MRI scans.Results Widening of the sylvian fissures and of the fluid spaces anterior to the temporal lobes was seen in 93% of cases. The mesencephalic cistern was also widened in 86%. Abnormal high-signal intensity on T2-weighted (T2-W) images was seen in the basal ganglia and periventricular white matter in 64% of children. Subdural collections were found in 3 patients, all of which resolved spontaneously. Four neonates followed with serial cranial US showed bilateral multiple caudothalamic cysts. Abnormal high signal on T2-W images was seen in the dentate nucleus, substantia nigra and the pontine medial lemniscus in 79, 43 and 64%, respectively.Conclusions Widening of the sylvian fissure, mesencephalic cistern and expansion of CSF spaces anterior to the temporal lobes are cardinal signs of GA-1. If combined with abnormalities of the basal ganglia and white matter, GA-1 should be strongly suspected.Presented at 37th Annual Congress of ESPR, Lisbon, Portugal, May 2000