Detection of low-fraction K-ras mutations in primary lung tumors using a sensitive method.

Mutations in the K-ras gene are often identified in lung tumors and are implicated in the development of lung cancer. We used a sensitive method to analyze low-fraction mutations occurring in codon 12 of the K-ras gene in 114 primary lung tumors, including 77 adenocarcinomas, 31 squamous cell carcinomas and 6 adenosquamous carcinomas, which had previously been shown to be negative for codon 12 K-ras mutation in a first screening using less sensitive methods. Sixteen of these tumors were found to contain a low-fraction mutation, including 9 mutations among the adenocarcinomas, six mutations among the squamous cell carcinomas and one mutation among the adenosquamous carcinomas. Our study also showed that the occurrence of low-fraction mutation was associated with a positive smoking history, as was previously found for the occurrence of high-fraction mutation. Patients with low-fraction mutations were younger (mean age 58.8 years) than those with either high-fraction mutations (63.2 years) or no mutation (66 years). Patients with low-fraction mutations were more often stage 1 (8 of 10) than patients with either high fraction mutations (22 of 44) or no mutation (33 of 71). Moreover, the overall survival was better for the group with a low-fraction mutation than both the high-fraction mutation group and the group with no K-ras mutation, but due to small sample size, the difference was not statistically significant. Our results suggest that using highly sensitive methods of K-ras mutant detection in tumor DNA could obscure differences between patients in whom the mutation is found throughout the tumor, those in whom the mutation is only present in a small subpopulation and those who have no mutation.

[6-methoxy-2-naphthylacetic acid level in plasma, synovial fluid and adjacent tissue in patients with rheumatoid arthritis or gonarthroses after a 4-day therapy with nabumetone (Arthaxan)]. / 6-Methoxy-2-Naphthylessigsäure-Spiegel in Plasma, Synovialflüssigkeit und umliegenden Geweben bei Patienten mit rheumatoider Arthritis oder Gonarthrosen nach 4tägiger Therapie mit Nabumeton (Arthaxan).

The concentration of 6-methoxy-2-naphthyl acetic acid (6-MNA) in plasma, synovial fluid, synovial tissue and fibrous capsule tissue was determined in an open study with 20 patients scheduled for knee joint surgery after oral treatment with nabumetone (Arthaxan) under steady state conditions. 6-MNA is the principal metabolite of the prodrug nabumetone arising from an extensive first-pass metabolism in the liver. The patients suffering from rheumatoid arthritis (n = 12) or osteoarthritis stage III or IV (n = 8) received a daily dose of 1 g nabumetone nocte starting 4 days prior to surgery. On day 1 an additional loading dose of 1 g nabumetone was given in the morning. At the time of surgery (day 5) simultaneously blood and synovial fluid was aspirated and after medial opening of the knee joint biopsies of synovial tissue and fibrous capsule tissue were taken. The samples were analysed employing HPLC. After 4 days of treatment mean 6-MNA concentration in plasma was 40.76 micrograms/ml, in synovial fluid 34.79 micrograms/ml, in synovial tissue 19.33 micrograms/g and in fibrous capsule tissue 11.43 micrograms/g. Under steady state conditions mean synovial fluid levels of 6-MNA were higher than after application of a single dose.

German drug monitoring studies with nabumetone.

Although randomised controlled comparative trials concerning the efficacy of the drug tested can produce reliable results in a limited number of selected patient groups, drug monitoring studies involving 10,000 patients or more are the methods of choice to detect rare adverse events. The aim of this drug monitoring study was to evaluate the efficacy and safety of dispersible nabumetone tablets. 8865 patients (46.2% male, 53.5% female, mean age 55 years, range 14.95) were involved in the investigation carried out by 1172 general practitioners. The disease indications comprised osteoarthritis (69.8%), soft-tissue rheumatism (11.3%), rheumatoid arthritis (9.9%) and soft tissue injuries (7.7%). Most of the patients (67.3%) received a daily dose of nabumetone 1 g for up to 6 weeks. Efficacy was evaluated at baseline, and after 1 week, 3 weeks and 6 weeks of treatment. With regard to global efficacy, overall improvement (symptoms resolved or markedly improved) was assessed in 82% of the patients. Elimination or at least significant improvement of pain on movement occurred in 95%, pain on pressure in 90% and pain at rest in 89% of the patients with symptoms. In relation to swelling, morning stiffness and joint mobility, elimination or at least significant improvement occurred in 79%, 80% and 82% of patients, respectively. 1846 patients (20.8%) had frequent periods of NSAID-related symptoms before treatment with nabumetone. A total of 1174 adverse events occurred in 850 patients (9.6%), most comprising minor gastrointestinal complaints. Considering that at least 25,000 patients have been documented in 2 German drug monitoring studies, it is therefore unlikely that any unexpected side effects will occur in the future. Consequently, nabumetone can be classified as an effective and safe NSAID.

Nasopharyngeal carcinoma. Brief review.

Nasopharyngeal carcinoma has a well-defined geographic distribution, primarily affecting persons from southern China and Southeast Asia. Environmental factors are numerous and appear to have a secondary role, mainly in the promotion of the neoplastic process. Relationship with the Epstein-Barr virus is indicated by the identification of viral genome copies within the cells and by a persistent host antibody response with restricted specificity for nasopharyngeal malignancies. The World Health Organization has recently adopted a histologic classification categorized into three subtypes according to the degree of epithelial differentiation, keratinization, and stromal lymphocytic infiltration. The tumor expands locally to contiguous structures, spreads through the cervical lymphatics following the jugular chain, and eventually metastasizes to the skeleton and liver. Primary management consists of radiation therapy to cervicofacial fields and usually offers adequate palliation, with a five-year median survival of 67 percent for stage I and 17 percent for stage IV disease.