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.     

Randomized controlled trial of dexamethasone treatment in very-low-birth-weight infants with ventilator-dependent chronic lung disease

This randomized controlled trial was designed to answer the question: does administration of dexamethasone to neonates with bronchopulmonary dysplasia decrease the need for assisted ventilation? Twenty-five infants with a birth weight < 1501 g, requiring mechanical ventilation and FiO₂ of ± 0.30 at 21-35 days of age, were randomized to treatment with iv dexamethasone or to sham injections for 12 days. The primary outcome criterion was extubation within seven days after study entry. Treatment (n= 12) and control (n= 13) groups were well matched at entry. Dexamethasone facilitated weaning from assisted ventilation (p= 0.0154). There was no increased incidence of infection. Dexamethasone treatment resulted in a significant increase in glucosuria (p= 0.0002) and in systolic blood pressure (p= 0.0034). There was a significant decrease in heart rate (p= 0.0001) and a significant weight loss (p= 0.0002) following dexamethasone treatment. Dexamethasone treatment facilitated weaning from assisted ventilation but several systemic effects were noted that deserve further evaluation before dexamethasone becomes routine treatment.     

Effects of positive and negative pressure ventilation on cerebral blood volume of newborn infants

The effects of intermittent positive airway and continuous negative extrathoracic pressure ventilation on cerebral blood volume in preterm infants were studied using near infrared spectroscopy. In 12 infants continuous negative extrathoracic pressure caused a median decrease in cerebral blood volume of 0.14ml/100ml brain (95% confidence intervals (CI) 0.035–0.280) compared with no respiratory support. Oxygenated and deoxygenated haemoglobin also decreased, implying increased venous drainage as the main effect. In 17 infants intermittent positive pressure ventilation also caused a median reduction in cerebral blood volume of 0.06 ml/100 ml brain (95% CI 0.010–0.115) compared with endotracheal positive airway pressure. Deoxygenated haemoglobin increased by 0.07 ml/100 ml brain (95% CI 0.010–0.100) while oxygenated haemoglobin decreased by O.lOml/lOOml brain (95% CI 0.005–0.175). The increase in deoxygenated haemoglobin implies decreased venous drainage and the decrease in oxygenated haemoglobin implies that other factors may also be significant. Heart rate, blood pressure and oxygen saturation were monitored continuously and remained stable.     

血清SOD、MDA、NO与突发性聋的相关研究

目的：通过对突发性聋病人血中一氧化氮（NO）、丙二醛（MDA）、超氧化物歧化酶（SOD）含量的检洲，探讨突聋与血氧自由基和自由基的清除剂SOD之间的关系。方法：采用硝酸还原酶法测定了30例突聋病人血中NO含量，并以25例同期体检正常的健康人为对照组；同时还用硫代巴比妥酸比色法测定MDA含量，用黄嘌呤氧化酶法测定SOD含量。砖呆；应用金纳多、能量合剂、克林臭（即马来酸桂哌齐特，钙通道阻滞药）联合静脉输入，突聋各组的听力均有不同程度提高，有效率在78．57％以上。治疗后同对照组相比，血清NO、MDA水平明显低于患病之初，而SOD活性明显高于治疗之前，P〈0．01。结论；检测突聋病人血中N0、MDA、SOD的含量，能帮助我们探讨突聋的发病机理，估计预后。血氧自由基的升高可能是突聋发病因素之一，而SOD的含量可以帮助我们估计预后。     

Primary osteosarcoma of the skull

Primary osteogenic sarcoma of the skull is an exceedingly rare condition. An adult male patient is described, who had a painless swelling in the right forehead that had rapidly enlarged in the previous 6 months. Radiological investigations showed a large destructive mass lesion involving the right side of the frontal bone with extension into the frontal sinus, causing marked extradural compression of brain parenchyma. Histopathological examination confirmed the lesion to be primary osteogenic sarcoma.     

Relations between age, metabolic control, disease adjustment and psychological aspects in insulin-dependent diabetes mellitus

The relations between age, metabolic control, disease adjustment, and psychological factors in boys and girls with recently diagnosed insulin-dependent diabetes mellitus (IDDM) were studied. Older girls had significant higher postremission glycosylated haemoglobin A (Hb A_lc) levels ( p = 0.008). Girls with more hospitalizations had a lower developmental level ( p = 0.05), and had significantly more problems in the behavioural rating ( p = 0.05). Boys with more hospitalizations had a more external locus of control ( p = 0.01), more difficulties with disease adjustment, more emotional problems, and were also clinically assessed as having more behavioural problems. Boys showing more difficulties in psychological adjustment to the disease also had higher postremission Hb A_1clevels ( p = 0.02). Although Swedish children with IDDM of short disease duration do not differ from healthy children in important psychological aspects, older girls and a small group of problematic younger boys are at risk of developing metabolic imbalance after a short disease duration.     

Metabolic effects of growth hormone treatment: an early predictor of growth response?

Fourteen children receiving one year of recombinant human growth hormone (rhGH) treatment underwent measurement of serial changes in body composition (measured by skinfold thickness, bioelectrical impedance, and H2(18)O dilution), resting energy expenditure (REE, estimated by ventilated hood indirect calorimetry), and total free living daily energy expenditure (TEE, measured by the doubly labelled water technique). Mean height velocity increased from 4.9 to 8.6 cm/year after six months of treatment. Fat free mass (FFM) increased more during the first six weeks (24.4 g/day) than from six to 26 weeks of treatment (6.8 g/day); fat mass decreased by 7.2 g/day and 1.1 g/day respectively. The six week increase in REE (kJ/day) was maintained after six months of treatment, though expressed per kilogram FFM (kJ/kgFFM/day), returned to pretreatment values by three months. Height velocity increases at six months correlated with six week changes in fat mass measured by skinfold thickness and REE, though use of this relationship to predict growth response in individuals is limited by the wide 95% prediction intervals. No significant changes in growth, body composition, or energy expenditure were observed between six and 12 months of treatment, in either patients who had initially responded well to treatment or those who were poor initial responders to treatment and who had their dose of rhGH doubled after six months.     

HIV-1tat induced apoptosis of T-cells is not mediated by TGF-β

Recent reports have demonstrated that the HIV-1 transactivator protein,tat, induces apoptosis in T-lymphocyte cell lines, as well as in peripheral blood mononuclear cells, and stimulates a cascade of events resulting in up-regulation of the potent immunosuppressive cytokine, transforming growth factor-β (TGF-β). In this study we evaluated the ability of TGF-β to mediatetat induced apoptosis in T-lymphocyte cell lines. T-cells treated exogenously with either TGF-β1 or a combination of tat and pan-specific TGF-β neutralizing antibodies showed little change in the amount of apoptosis. When treated with pan-specific TGF-β neutralizing antibodies, Jurkat cells that stably expresstat protein (Jurkat-tat) showed only a modest decrease in apoptosis, while CEM-TART cells (CEM T-cells expressing both HIV-1tat andrev) demonstrated little change in the amount of apoptosis. In conclusion, we have demonstrated that TGF-β does not play a significant role in mediatingtat induced T-cell apoptosis.