Relationship between epidermal growth factor receptor mutations and skin rash in non-small cell lung cancer patients.

Several reports have investigated relationships between epidermal growth factor receptor (EGFR) mutations and the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer; however, there have been insufficient analyses of relationships between EGFR mutations and adverse reactions. This study investigated the relationships between EGFR mutations and skin rash. We first compared skin rash grades between different mutations, then tested factors possibly affecting skin rash by multivariate analysis. The main outcome measure was the significant difference in incidence of skin rash between each group with different mutations. Our study suggested that the risk of skin rash is low in patients with exon 19 deletion mutations who are taking EGFR-TKIs, whereas it is high in those with exon 21 point mutations. These results will be useful indicators for instructions regarding daily examinations, skin care, and use of oral antibiotics or topical steroids in patients taking EGFR-TKIs with skin rash.

Detection of gastric cancer using 18F-FLT PET: comparison with 18F-FDG PET.

PURPOSE: We prospectively investigated the feasibility of 3'-deoxy-3'-(18)F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of gastric cancer, in comparison with 2-deoxy-2-(18)F-fluoro-D-glucose (FDG) PET, and determined the degree of correlation between the two radiotracers and proliferative activity as indicated by Ki-67 index. METHODS: A total of 21 patients with newly diagnosed advanced gastric cancer were examined with FLT PET and FDG PET. Tumour lesions were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUV) was calculated. RESULTS: For detection of advanced gastric cancer, the sensitivities of FLT PET and FDG PET were 95.2% and 95.0%, respectively. The mean (+/-SD) SUV for FLT (7.0 +/- 3.3) was significantly lower than that for FDG (9.4 +/- 6.3 p < 0.05). The mean FLT SUV and FDG SUV in nonintestinal tumours were higher than in intestinal tumours, although the difference was not statistically significant. The mean (+/-SD) FLT SUV in poorly differentiated tumours (8.5 +/- 3.5) was significantly higher than that in well and moderately differentiated tumours (5.3 +/- 2.1; p < 0.04). The mean FDG SUV in poorly differentiated tumours was higher than in well and moderately differentiated tumours, although the difference was not statistically significant. There was no significant correlation between Ki-67 index and either FLT SUV or FDG SUV. CONCLUSION: FLT PET showed as high a sensitivity as FDG PET for the detection of gastric cancer, although uptake of FLT in gastric cancer was significantly lower than that of FDG.

Detection of hepatocellular carcinoma using 11C-choline PET: comparison with 18F-FDG PET.

UNLABELLED: The purpose of this study was to retrospectively investigate the feasibility of 11C-choline PET, compared with 18F-FDG PET, for the detection of hepatocellular carcinoma (HCC). METHODS: A total of 16 HCC lesions in 12 patients were examined with both 11C-choline PET and 18F-FDG PET. Tumor lesions were identified as areas of focally increased uptake, exceeding that of surrounding noncancerous liver tissue. For semiquantitative analysis, the tumor-to-liver (T/L) ratio was calculated by dividing the maximal standardized uptake value (SUV) in HCC lesions by the mean SUV in noncancerous liver tissue. RESULTS: 11C-choline PET showed a slightly higher detection rate than did 18F-FDG PET for detection of HCC (63% vs. 50%, respectively), although this difference was not statistically significant. 11C-choline PET had a better detection rate for moderately differentiated HCC lesions but not for those poorly differentiated (75% vs. 25%, respectively). In contrast, 18F-FDG PET exhibited the opposite behavior, with corresponding detection rates of 42% and 75%, respectively. The mean 11C-choline SUV and T/L ratio in moderately differentiated HCC lesions were higher than those in poorly differentiated HCC lesions. In contrast, the mean 18F-FDG SUV and T/L ratio in poorly differentiated HCC were higher than those in moderately differentiated HCC. These differences, however, were also not statistically significant. CONCLUSION: 11C-choline PET had a better detection rate for moderately differentiated HCC lesions but not for poorly differentiated HCC lesions, whereas 18F-FDG PET produced the opposite result. 11C-choline is a potential tracer to complement 18F-FDG in detection of HCC lesions.

[Infection treatment caused by multiple-drug-resistant Pseudomonas aeruginosa in a patient undergoing allogeneic hematopoietic stem cell transplantation].

Infections caused by multiple-drug-resistant Pseudomonas aeruginosa (MDRP) are a clinically significant problem. We reported here the effective use of combination therapy in a patient with infection caused by MDRP according to an interventional treatment strategy suggested by a pharmacist. The patient was a 70-year-old male who underwent allogeneic hematopoietic stem cell transplantation. On day 45 after transplant, MDRP was newly isolated from urine, but the diagnosis at that time was colonization. On day 61, the patient developed a fever (> or =38.0 degrees C). In addition, laboratory data showed that C-reactive protein (CRP) was also increased. At the medical team conference, the pharmacist proposed the following treatment strategy for this infection. Aztreonam and amikacin were intravenously administered at doses of 2 g/day and 800 mg/day, respectively. The subsequent clinical course was well controlled, but the infection recurred and was aggravated. Aztreonam and ciprofloxacin were then intravenously administered at doses of 4 g/day and 600 mg/day, respectively, resulting in the alleviation of fever in the patient as well as a decrease in CRP and disappearance of MDRP isolates from urine on day 67; that is, MDRP infection was consequently well controlled. In conclusion, the combination therapy between aztreonam and amikacin, or ciprofloxacin may be clinically useful for severe infections of MDRP in compromised hosts.

Tunnel Technique for the Closure of an Oroantral Fistula with a Pedicled Palatal Mucoperiosteal Flap.

BACKGROUND: Oroantral fistula may develop as a complication of tooth extraction owing to infection, trauma, or removal of maxillary cyst or tumors. Closure by using a palatal mucoperiosteal flap with the greater palatine vessels is a very traditional and basic technique. The palatal mucosa is thick and is firm. However, deformation can occur with shifting of the mucoperiosteal flap, survival of the flap may be unsuccessful, and patients may have substantial intraoral discomfort felt until healing of the eminence with the arcuation. As a method to relieve these problems, we present a mucoperiosteal tunnel technique for the closure of oroantral fistula by using a palatal mucoperiosteal flap pedicled with the greater palatine vessels. METHOD: A 42-year-old man and a 69-year-old woman each had a palatal fistula after palatal tumor resection and tooth extraction, respectively. We designed a mucoperiosteal flap pedicled with the left greater palatine vessel. We ablated the mucoperiosteum between the fistula and the mucoperiosteal flap, and passed this flap under the ablated mucoperiosteum as a tunnel. RESULT: One year after surgery, the fistula had not reappeared and the mucoperiosteal flap harvest did not generate dyskinesis of the soft palate. CONCLUSION: Tunnel technique for the closure of an oroantral fistula with a pedicled palatal mucoperiosteal flap is obtains good fructification.

High-level expression of clostridial sialidase using a ferredoxin gene promoter-based plasmid.

A "large" sialidase isozyme (NanI) from Clostridium perfringens is a representative microbial sialidase with broad substrate specificity, being used for the analysis of sialoglycoconjugates. It is also a possible virulence factor. However, purification of the native enzyme in a large quantity is not practical due to its low productivity. To obtain the enzyme in a satisfactory yield, a gene encoding the NanI was transcriptionally fused to the fdx gene promoter (P(fdx)) in a shuttle-vector, pFF, and transformed into C. perfringens 13. The resultant strain released the enzyme into the culture medium, as the original strain does. The enzyme activity increased during the first 6 h of culture and thereafter remained at maximal levels. The maximal activity was approximately 3000-fold compared with that of the original strain, and 15-fold compared with that of recombinant Escherichia coli, which possesses extra copies of the tRNA gene for selected rare codons. This suggests the usefulness of a P(fdx)-based plasmid for expressing AT-rich genes in C. perfringens. The enzyme was successfully purified by two-step procedure with a specific activity of 2860 U/mg using 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid and a yield of 1.69 mg of NanI per 100 ml of culture. The method described here can facilitate purification of NanI in enough quality and quantity to analyze the role of sialoglycoconjugates in cells and the pathogenic importance of NanI sialidase.

A novel type of DNA curvature present in a Clostridium perfringens ferredoxin gene: characterization and role in gene expression.

This study has revealed that a Clostridium perfringens ferredoxin gene (per-fdx) possesses a novel type of DNA curvature, which is formed by five phased A-tracts extending from upstream to downstream of the -35 region. The three A-tracts upstream of the promoter and the two within the promoter are located at the positions corresponding to A-tracts present in a C. perfringens phospholipase C gene (plc) and a Clostridium pasteurianum ferredoxin gene (pas-fdx), respectively. DNA fragments of the per-fdx, pas-fdx and plc genes (nucleotide positions -69 to +1 relative to the transcription initiation site) were fused to a chloramphenicol acetyltransferase reporter gene on a plasmid, pPSV, and their in vivo promoter activities were examined by assaying the chloramphenicol acetyltransferase activity of each C. perfringens transformant. Comparison of the three constructs showed that the order of promoter activity is, in descending order, per-fdx, pas-fdx and plc. Deletion of the three upstream A-tracts of the per-fdx gene drastically decreased the promoter activity, as demonstrated previously for the plc promoter. Substitution of the most downstream A-tract decreased the promoter activities of the per-fdx and pas-fdx genes. These results indicate that not only the phased A-tracts upstream of the promoter but also those within the promoter stimulate the promoter activity, and suggest that the high activity of the per-fdx promoter is due to the combined effects of these two types of A-tracts.