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.     

The Fremantle Lead Study

Objective: To ascertain blood lead levels in a sample of preschool children from Fremantle, Western Australia, and to correlate these with possible risk factors.
Methodology The study was a cross-sectional prevalence survey of 120 children from day-care centres and 44 hospital inpatients. Blood lead and ferritin levels were determined and a risk factor questionnaire was completed by parents.
Results Of the 164 children 25.6% had lead levels above the NH&MRC goal (<10μg/dL). Nine of 133 (6.7%) had ferritin levels below 10 μg/L suggesting iron deficiency. Excessive blood lead concentrations as defined by the NH&MRC (>9μg/dL) related to: child's presence during house renovation (OR 3.35, P = 0.007, 95% Cl 1.39-8.81); Aboriginality (OR 6.4, P = 0.008, 95% Cl 1.6-24.9), and, in the 9-24 month age group, inversely to distance between home and a road carrying >7000 vehicles/day (r-0.56, P = 0.009, n = 24).
Conclusions A group of Fremantle children with unacceptably high blood lead levels has been identified. Renovation of older housing and Aboriginality are important risk factors.     

One-year longitudinal evaluation of neuropsychiatric symptoms in Alzheimer's disease. The REAL.FR Study

Behavioral and Psychological Symptoms are major and frequent manifestations of Alzheimer's Disease (AD). The aim of the present study was to evaluate neuropsychiatric symptoms in the PHRC REAL.FR cohort (for Réseau sur la maladie d'Alzheimer Fran?ais) after one year of evolution. Four hundred and eighty two patients with mild and moderate AD were assessed. A majority of them had significant symptoms at inclusion (85.3 % of subjects with mild AD, 89.7% of patients with a moderate AD). Patients with mild AD had a significant increase of the Neuropsychiatric Inventory (NPI) frequency x severity scores for apathy and aberrant motor behavior. Patients with moderate AD had a significant increase of NPI disinhibition, aberrant motor behavior and sleep disorders scores. The variation of NPI total score at one year correlated positively with change in Zarit's caregiver burden score, independently of global cognitive evolution. After one year, a group of 54 patients were institutionalized in nursing home or long term care unit. When compared to non institutionalized patients, the institutionalized group was characterized at base line by a lower MMSE score, a higher Zarit caregiver burden score, and a higher NPI agitation and disinhibition scores.     

Role of behavioural disturbance in the loss of autonomy for activities of daily living in Alzheimer patients

BACKGROUND: Cognitive impairment is associated with functional impairment in patients with Alzheimer's disease (AD). Behavioural disturbance is very common in these patients. Nevertheless, there has been very little research into the relations between behavioural disturbance and functional status in AD. The purpose of this study is to investigate the relationship between behavioural disturbance and functional status after taking account of cognitive impairment. MATERIAL AND METHODS: 579 patients were prospectively evaluated at 16 French hospitals, all referents for AD, and were diagnosed with possible or probable AD. These patients were assessed with NeuroPsychiatric Inventory (NPI), cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), Clinical Dementia Rating scale (CDR) and Instrumental Activities of Daily Living scale (IADL). RESULTS: The number of men with available data for IADL total score was too small to make any analysis. 'Group A' gathered 256 women for whom the relation between autonomy for Activities of Daily Living (ADL) and the other variables were determined. 'Group B', pooled 85 women for whom relations found were verified. Linear regression was used for the analysis. With age, cognitive impairment allows us to explain best (38%) the loss of autonomy for ADL. CONCLUSION: The role of behavioural disturbances in the loss of autonomy for ADL was not determinant in our study, whereas cognitive impairment and age were better able to determine the loss of autonomy for ADL. Further study is needed to explain the decline of functional status in AD patients.