Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.     

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.     

5-HT2A receptor antagonist properties of cyamemazine in rat and guinea pig smooth muscle

5-HT(2A) receptor antagonism seems to explain the low incidence of extrapyramidal side effects with atypical neuroleptics. Whether the neuroleptic cyamemazine, which at low doses is also devoid of extrapyramidal side effects, possesses 5-HT(2A) receptor antagonist properties is unknown. Cyamemazine was tested for its ability to antagonize 5-HT(2A)-mediated responses in isolated rat aorta and guinea pig trachea and to displace [3H]ketanserin specifically bound to rat brain membranes. In isolated rat aorta, cyamemazine potently and competitively antagonized serotonin-dependent contractions (pA(2)=8.82+/-0.26, n=7; Schild's slope=1.02+/-0.29). In this test, cyamemazine was of similar potency as ketanserin (pA(2)=8.23). In isolated guinea pig trachea, cyamemazine reduced maximum contractile responses to serotonin with pIC(50)=7.92+/-0.35, (n=4), whereas ketanserin exhibited a pIC(50)=8.79. Finally, cyamemazine displaced [3H]ketanserin specifically bound to rat brain membranes with pK(i)=8.76+/-0.53 (n=3). In conclusion, cyamemazine behaves as a potent antagonist at 5-HT(2A) receptors, which compares well with the reference compound, ketanserin. Whether this 5-HT(2A) receptor antagonist action of cyamemazine can explain its low incidence of extrapyramidal side effects deserves further investigation.     

Folic acid and prevention of anomalies of foetal neural tube closing in women treated for epilepsy

Anomalies of neural tube closing are serious malformations which are encountered most often in babies of epileptic women treated with anti-epileptic drugs during pregnancy. Dietary supplementation of folic acid has been suggested as a preventive measure in these cases, based on the long suspected association between folic acid deficiency and congenital malformations. Folic acid deficiency usually results from insufficient dietary intake, or increased requirements during pregnancy. Moreover, certain anti-epileptic drugs can reduce the availability of folic acid. In secondary prevention, the protective effect of folic acid has been clearly demonstrated, whilst epidemiological data suggest that such treatment is also useful in primary prevention. With respect to women with epilepsy, there is a clear consensus as to the interest of dietary supplementation with folic acid before conception and during the first three months of pregnancy (the period of organogenesis), particularly given the fact that side-effects are extremely rare. Apart from recurrence prevention, where a dose of 4mg/day is recommended, no standard dosing guidelines exist. We would suggest that this same dose be used for epileptic patients in pregnancy, particularly if they are treated with barbamazepine or valproic acid.     

Initial experiences with 123-Iodine-IBZM neuroreceptor scintigraphy in extrapyramidal disorders

The receptor scintigraphy of the dopaminergic system of the brain is of interest in the evaluation of movement disorders. The 123I-IBZM is a radiopharmaceutical with affinity predominantly to postsynaptic D2 receptors. The aim of this study was to evaluate the role of IBZM SPECT investigations in the differentiation of disorders with Parkinson's syndrome. Eight patients with idiopathic Parkinson's syndrome and 8 patients Parkinson's syndrome with other etiology were investigated with 123I-IBZM SPECT (6 females, 10 males, mean age +/- SD: 59 +/- 9). The patients according to the clinical signs and symptoms, results of CT/MRI and rCBF SPECT investigation were categorized. The reconstructed SPECT slices were evaluated visually and quantitatively. The visual interpretation of the images were performed by two observer and scored the radiopharmaceutical uptake (from 1-3) of the cortex and the striatum separately. For quantification striatum/frontal cortex activity ratio were calculated with ROI technique. The differences between the patient groups were statistically analyzed by two tailed t-test. The IBZM uptake were different in the two group of patients. The striatal IBZM accumulation was higher in the idiopathic Parkinson's syndrome patients compared to the other parkinsonians. The striatum/frontal lobe activity ratio was 1.69 +/- 0.9 (mean +/- SD) in the right, 1.67 +/- 0.04 (mean +/- SD) in the left hemisphere of the patients with idiopathic Parkinson's syndrome. The corresponding data in the nonidiopathic parkinsonian group were 1.53 +/- 0.06 (mean +/- SD), 1.52 +/- 0.04 (mean +/- SD) respectively (p < 0.01). The quantitative data correlated with the results of the visual evaluation. According to the data presented IBZM-SPECT is an effective tool in the differentiation of disorders with Parkinson syndrome.     

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.     

Early-onset diabetic coronary macroangiopathy in young diabetes: two case reports

Macroangiopathy is multifactorial. It is more severe and frequent in association with nephropathy in diabetes mellitus (DM), being the first cause of mortality in both types of DM. Nevertheless, it is poorly understood in young patients. We report on 2 young diabetic patients with early-onset coronary disease. Case 1, 40 yo, Caucasian, female, type 2 DM for 21 y: treated with sulphonylureas until 25 y, she was switched to insulin upon becoming pregnant. Preeclampsia ensued, but no premature delivery occurred. Macroproteinuria remained (0.99 g/24 h), and she progressed to renal failure (clearance 52.7 mg/min) (conservative treatment). At age 36, she had an acute myocardial infarction. Severe tri-arterial disease was diagnosed, and coronary bypass grafting (CABG) performed. Case 2, 34 yo, black, female, type 1 DM for 24 y: diagnosed by diabetic ketoacidosis. Due to poor metabolic control (HbA1c chronically above 4 points beyond upper limit for normal) she progressed to microalbuminuria (0.26 g/24 h) at age 22, after pregnancy. Macroproteinuria (1.7 g/24 h) ensued after a second pregnancy. At 31 y, she presented with stable angina. After coronary angiography, CABG was indicated. These two cases of macroangiopathy in patients diagnosed with DM at an early age show acceleration in the development of coronary disease, suggesting aggressive multifactorial approach of related risk factors from the beginning, regardless of its etiology.