Conservative surgical management of patients with bisphosphonate-related osteonecrosis of the jaws: a series of 120 patients.

We evaluated retrospectively the efficacy of local resection for patients who presented with bisphosphonate-related osteonecrosis of the jaw (BRONJ). We studied 120 subjects with who required local resection of 129 BRONJ lesions that had not responded to medical treatment. The primary outcomes were improvement of the clinical stage of BRONJ and resolution of disease, and the secondary outcome was the influence of the surgeon's experience on the healing of the lesions. Age, sex, underlying diseases, smoking, and coexisting conditions were recorded. Logistic regression analysis was used to isolate factors that could potentially affect the outcome. Most of the lesions (n=107, 84%) improved postoperatively, 20 showed no change, and one got worse. One patient died. Stratification indicated complete healing and total resolution of disease for all 26 stage I lesions, improvement for 67 of the 77 stage II lesions, and for 14 of the 25 stage III lesions. The disease resolved in 67 of the 69 stage II lesions, and 14 of the stage III cases. Logistic regression indicated that smoking and the stage of disease could affect the outcome. Analysis of the surgeons' learning curve showed that performance improved significantly over time. Complete healing after local resection increased from 40% to 80% over a period of eight years (p<0.001). We conclude that local resection may be the treatment of choice in BRONJ stages I and II. Stage III might be better treated with either resection or clinical monitoring according to the condition of the patient.

Risk factors influencing BRONJ staging in patients receiving intravenous bisphosphonates: a multivariate analysis.

The objective of this study was to determine, retrospectively, the influence of various risk factors on the staging of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a population attending a department of dentistry and oral surgery in Italy. Data were collected from the electronic and paper medical records of 90 patients receiving intravenous bisphosphonates. Two experienced and calibrated examiners used the American Association of Oral and Maxillofacial Surgeons updated 2009 classification to record the stage of BRONJ lesions. Multivariate ordinal logistic regression was performed to determine individual risk factors negatively affecting BRONJ staging. The factors associated with a worse BRONJ staging were high bisphosphonate cumulative dose (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.02-2.82; P=0.04), smoking (OR 1.80, 95% CI 1.03-2.80; P=0.04), steroid intake (OR 1.70, 95% CI 1.00-2.87; P=0.05), and a maxillary location of the lesion (OR 3.50, 95% CI 1.81-6.77; P<0.01). Tooth extraction was the event that most negatively influenced BRONJ staging (OR 1.60, 95% CI 1.00-2.81; P=0.05), in comparison to other events such as prosthetic trauma, implant treatment, oro-dental infection, and periodontal disease. Certain clinical and medical risk factors may determine a more severe staging of BRONJ lesions. Future studies are necessary to confirm these findings.

Programmes and activities of the International Centre for Pesticide Safety.

The International Centre for Pesticide Safety (ICPS) is a research unit of the National Health Service created by the Government of the Region of Lombardy at the proposal of the World Health Organization-Regional Office for Europe, in cooperation with the University of Milan, and in agreement with the Italian Ministry of Health. ICPS operates in the following areas of activity: information and documentation on pesticide toxicity to man and environment, epidemiological, toxicological and clinical research on effects of pesticides in man; training and education of personnel in public health, assessment of environmental and health impact of pesticides by means of Geographical Information Systems, laboratory research for development and standardisation of methods for residue measurement in environmental and biological media. ICPS is also a centre of international meetings and continuing education courses. A number of projects carried out or underway at ICPS are briefly described in this paper.

The International Centre for Pesticide Safety.

The International Centre for Pesticide Safety (ICPS) was inaugurated in March 1990. Coordinated by the World Health Organization (WHO) and in collaboration with research and university institutions, the Centre operates in the following areas of activity: information and documentation on pesticide toxicity; epidemiological, toxicological and clinical research; training and education; laboratory research. ICPS is also a centre of meetings and courses on permanent education. This paper reports on the activities carried out so far and on the future programmes of ICPS.

The 1:1 N-NS protein complex of vesicular stomatitis virus is essential for efficient genome replication.

We studied the effect pH had on the N-NS protein complex to determine its role in vesicular stomatitis virus (VSV) genome replication, as we had previously shown that VSV genome replication in vitro requires the interaction of the viral N and NS proteins into a 1:1 complex. A previous report showed that the growth of VSV in L cells was sensitive to the pH of the environment (M. Fiszman, J. B. Leaute, C. Chany, and M. Girard, J. Virol. 13:801-808, 1974). We hypothesized that low pH might disrupt the N-NS protein complex, and so we investigated the molecular events leading to inhibition of viral RNA replication in vitro from extracts that were prepared from VSV-infected cells incubated at pH 6.6. We found that viral genome RNA synthesis in vitro was reduced when infected cells were maintained at pH 6.6. Through immunoprecipitation analysis of the viral soluble protein pool, we found that a complex that usually exists between the N and NS proteins at pH 7.4 was altered in extracts from infected cells maintained at pH 6.6, and this was responsible for the observed effects on viral replication. The effect of low pH on the N-NS protein complex could not be abolished by increasing the concentration of the altered complex, indicating that the effects is more than simply a decrease in the level of the protein complex in the cell. Our data provide additional evidence that the 1:1 N-NS protein complex, and not the N protein alone, serves as the substrate for viral RNA replication in vivo.

The WHO-UNDP epidemiological study on the health effects of exposure to organophosphorus pesticides.

A multinational epidemiological study on the neurotoxic effects of long-term, low-level exposure to organophosphorus pesticides (OPs) is being supported in ten European countries by the United Nations Development Programme (UNDP) jointly with the World Health Organization (WHO) Regional Office for Europe. The protocol developed for the study is directed at the assessment of OP exposure and absorption, abnormal neurological findings, and behavioral changes in both agricultural and industrial workers. The biological monitoring tests adopted in the study have been standardized and submitted to quality assurance programmes.