Mathematical modelling in risk/exposure assessment of tobacco related lung cancer

The existence of a dose-related increase of lung cancer riskin cigarette smokers has been indisputably established. Thisfinding, however, is not confirmed at low doses (< 5 cigarettes/day),there still being a lack of epidemiological data. The use ofmathematical models of carcinogenesis to extrapolate from higherdoses allows estimation of the risk for very light smokers.The present study has been designed to compare a set of mathematicalmodels, i.e. one-hit, two-stage, multi-stage, logit, probit,and Weibull, in extrapolating relative risks at low doses fromthe data of nine large cohort studies on cigarette smokers reportedin the IARC Scientific Monograph on tobacco smoking. All modelsevaluated, apart from the one-hit, achieved a good fit, withthe proportion of explained variance ranging between 61% and67%. The relative risk estimates for passive smokers from themost updated epidemiological studies were taken into accountto evaluate, on the basis of these models, the correspondingexposure in terms of ‘cigarette equivalent’ smoked.These values ranged from 0.21 to 0.43 cigarettes/day for thetwo-stage and multistage model, while probit, logit and Weibullmodels, yielded estimates one or even two orders of magnitudelower. The authors emphasize the substantial agreement betweenthe estimates of ‘cigarette equivalent9 based on the applicationof two-stage and multi-stage models to the epidemiological evidenceon the effect of passive smoking and to the data based on thecomparison of tobacco metabolites in active and passive smokers.     

High serum levels of tumour necrosis factor‐α and interleukin‐8 in severe asthma: markers of systemic inflammation?

BACKGROUND: Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma. OBJECTIVE: To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels. METHODS: We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89+/-3] and 14 severe asthmatics [FEV1(%pred): 49+/-2]. RESULTS: IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P<0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild-moderate asthmatics (P<0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics. CONCLUSION: sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma.     

The brain as a target for adrenocortical steroids: cognitive implications.

It is well established that a reciprocal control exists between the brain and glucocorticoid hormones. The brain regulates adrenocortical function via hypothalamic corticotrophin releasing hormone-41 (CRH-41), glucocorticoids act at specific receptors in the hippocampus, thus promoting negative feedback mechanisms. Because the hippocampus is a major site for memory processes, a role for excessive/long-lasting plasma glucocorticoid levels has been suggested in conditions of mental impairment. Major depression, Cushing's disease, and dementia of the Alzheimer type are disorders which share hyperactivity of the hypothalamo-pituitary-adrenal axis, as well as symptoms of cognitive decline. Although the mechanisms leading to hypercortisolemia appear to be different in each case, the neuropsychological features of these three disorders accord with the hypothesis of glucocorticoid-associated brain damage. It therefore is important to find pharmacological strategies that will avert or reduce these potential consequences on brain function.     

术中射频消融后病灶刮除治疗脊柱转移瘤

目的:探讨术中射频消融(RFA)后再行病灶刮除术治疗脊柱转移瘤的可行性及疗效.方法:2004年～2006年,对11例脊柱转移瘤患者术中实施RFA后再行病灶刮除术,将FRA前后病灶标本进行光镜和电镜病理检查,随访患者疼痛缓解情况及肿瘤复发情况.结果:术中未出现脊髓和神经根损伤,RFA后瘤组织固缩,刮除顺利,出血量350～3800ml,平均1024.5ml.全部病例得到6个月以上随访,平均9.8个月,全部患者生存期超过6个月,VAS评分术前平均5.8分,术后6个月时平均1.9分.1例出现局部肿瘤复发.RFA前的标本光、电镜检查均未见肿瘤组织坏死.RFA后光镜检查3例无明显坏死,9例肿瘤细胞完全坏死:电镜检查10例肿瘤细胞完全坏死,1例肿瘤细胞部分坏死,1例无明显坏死.结论:术中RFA后再行病灶刮除治疗脊柱转移瘤安全可行,有利于肿瘤的刮除,减少局部复发的风险.     

Effects of atorvastatin on arterial endothelial function in coronary bypass surgery

Objective: Endothelial dysfunction represents a critical early component of organ injury following cardiopulmonary bypass. Recent studies demonstrate that the treatment with atorvastatin is associated with a significant improvement of endothelial function independently of its efficacy on cholesterol levels. Therefore, we investigated the effects of preoperative atorvastatin treatment on endothelium function after coronary surgery. Methods: Forty patients undergoing coronary surgery were randomized to treatment with atorvastatin (20 mg/die; N = 20) or placebo (N = 20) 3 weeks before surgery. Twenty normal patients served as control group. The flow-mediated dilations (FMD) of the brachial artery after both reactive hyperemia (endothelium dependent) and nitroglycerin administration (endothelium independent) were evaluated at baseline, at 48 h, and 5 days postoperatively. Results: At baseline, the endothelium-dependent FMD was significantly attenuated in coronary versus normal patients (normal 10.3 ± 1.8% vs coronary 4.1 ± 1.6%, p < 0.01). At 48 h postoperatively all patients exhibited a reduced FMD compared with baseline values: the endothelium-dependent dilatation showed a drop of 60.1 + 15% in the patients of the placebo group compared with 45.8 + 16.6% (p < 0.05) those in the atorvastatin group. At the univariate analysis, no significant correlation was found between serum levels of either total cholesterol or HDL cholesterol and FMD. The nitroglycerin-induced dilation was not significantly influenced by extracorporeal circulation as well as by atorvastatin treatment. Conclusions: The endothelial dysfunction following cardiopulmonary bypass is improved by the treatment with atorvastatin, by a mechanism unrelated to the drug efficacy of controlling serum cholesterol levels.     

Early reconstruction of the abdominal wall in giant omphalocele.

Omphalocele is the most common congenital defect of the abdominal wall. Mortality rate is between 20 and 70% and early closure of the abdominal wall, within 10 days of life, is vital to the successful outcome of the surgical treatment. The authors describe the use of two bipedicled flaps of abdominal skin to correct the defect of the midline as soon as the reduction of all viscera has been accomplished.     

MR findings in pituitary haemosiderosis

A girl with Diamond-Blackfan syndrome and hypopituitarism was suspected of having pituitary haemosiderosis because of the clinical picture and the long history of blood transfusions. On T1-weighted MR images the pituitary exhibited a markedly hypointense anterior lobe (mimicking the empty sella), suggesting iron deposition, while on T2W MRI the low signal of the pituitary was surrounded by the high signal of the CSF. MR may be considered the examination of choice for detecting iron overload in the pituitary. Received: 10 November 1997 Accepted: 21 November 1997