In vitro metabolism and toxicity assessment of toxin T-514 (Peroxisomicine A1) of Karwinskia humboldtiana in microsomes and primary cultured hepatocytes.

T-514 (Peroxisomicine A(1)) from Karwinskia humboldtiana is a dimeric hydroxyanthracenone with a highly selective cytotoxic effect on tumor cells. We evaluated the metabolism of this compound in two in vitro systems (liver microsomes and hepatocytes) and assessed the cytotoxicity of its metabolites on normal and tumor cells. Microsomes (12.5, 125 and 250 microg of protein/ml) and hepatocytes (1 x 10(6) cells/ml) were incubated with the toxin (25 microM) for 0.5, 1, 3, 6, 9, 12 and 24 h and the samples were examined using chromatographic analysis and UV spectra. Two metabolites (M1 and M2) were detected in the rat microsomes and one (M1) in the monkey microsomes. The retention times and UV spectra of the peaks were very similar to those of the toxin T-514. M1 was isolated and identified as a mixture of two isomers. The cytotoxicity of the metabolites was evaluated in Chang liver and Hep G2 cells but they did not show the selective cytotoxic effect on tumor cells seen in the original compound.     

Is there a role for reconstructive techniques to prevent periodontal defects after third molar surgery?

PURPOSE: Among patients at high risk for second molar (M2) periodontal defects after third molar (M3) removal, does active treatment at the time of extraction, when compared with no treatment, alter the risk of postextraction M2 periodontal defects? MATERIALS AND METHODS: We used a prospective cohort study design and a sample composed of subjects at high risk for developing M2 periodontal defects after M3 extraction, that is, age > or = 26 years, pre-existing periodontal defects (attachment level [AL] > or = 3 mm), and mesioangular or horizontal M3 impaction. The predictor variable was treatment status of the M3 extraction site. The M3 extraction sites were reconstructed with demineralized bone powder (DBP), bioresorbable guided tissue regeneration (GTR) therapy, or no treatment. The outcome variable was ALs measured at the M2 distobuccal line angle preoperatively and 26 weeks after extraction. Appropriate univariate, bivariate, and multivariate statistics were computed, and statistical significance was set at a value P < .05. RESULTS: The cohort was composed of 12 subjects contributing 18 high-risk M3s. Twenty-six weeks after M3 removal, the ALs for GTR-treated (3.0 +/- 1.2 mm), DBP-treated (1.4 +/- 0.5 mm), and control (3.8 +/- 0.9) M3 sites were statistically significantly different ( P = .002). Tukey post-hoc comparisons revealed a statistically significant difference between control and DBP ALs ( P = .001) and GTR-treated and DBP-treated ALs ( P = .037). There was no statistically significant difference in ALs between control and GTR-treated M3s ( P = .35). CONCLUSIONS: The results of this study suggest that subjects at high risk for developing M2 periodontal defects after M3 removal may benefit from the use of DBP placed at the time of M3 extraction to enhance periodontal healing.     

Practical management of patients with non-small-cell lung cancer treated with gefitinib.

PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.     

Diabetes mellitus as a contributory factor in oral candidosis.

It has been reported that poor glycaemic control predisposes to oral candidal infection in diabetic patients. For instance, the carriage of Candida species and the density of candidal growth in the oral cavity is frequently claimed to be increased in patients with diabetes mellitus. However, the validity of these observations remains controversial. Hence, we review and discuss here the clinical data in the literature on the relationship between diabetes and oral candidal carriage and infection, and possible mechanisms associated with its pathogenicity.     

The galea fascia flap in orbital reconstruction: innovative harvest technique.

AIM: To report the treatment of a recurrent adenoid-cystic carcinoma of the lacrimal gland required orbital exenteration with an en bloc resection of the lateral orbital rim and wall and an anterior portion of the temporal muscle. Reconstruction was planned with both the objectives of a shortened healing time for faster epithetic reconstruction and no visible scars. METHOD: After a cranially extended temporal approach, the dissection of the superficial galea layer was connected with the subcutaneous dissection of the upper and lower eyelid after subciliary incisions. RESULTS: Ample exposure of the temporal, frontal and orbital region was obtained, facilitating the orbital exenteration with en bloc resection of the lateral orbital rim and wall and the anterior portion of the temporal muscle. The epithelialization of the eye socket covered with the galea fascia flap was accelerated, providing faster epithetic reconstruction, without visible scars. CONCLUSIONS: Healing time is accelerated, providing faster epithetic rehabilitation without visible scars, which is important in the postoperative rehabilitation ladder after eye exenteration for both patient and surgeon. Further more ablative surgery within this region gets safer and easier due to the ample exposure of this innovative surgical technique. Further evaluation of the effectiveness and safety of this new approach is advisable.     

Normal obstetric ultrasound reduces the risk of Down syndrome in fetuses of older mothers

The objective of this study is to determine whether a normal fetal morphology ultrasound scan in women older than 35 years reduces the risk of aneuploidy. We reviewed the results of amniocentesis and second trimester sonogram in all women older than 35 years from 1991 to 1995. None had prior screening. We excluded fetuses with structural anomalies. We determined the sensitivity and specificity of minor markers in detecting Down syndrome and also determined the reduction in risk of a normal sonogram. Among the 2060 women older than 35 years giving birth during the study period, 16 (0.78%) delivered an infant with Down syndrome. Of the 16 fetuses, two had no prenatal testing or ultrasound, two had invasive testing but no second trimester sonogram, five had a normal sonogram and seven had one or more sonographic markers of Down syndrome. At least 17% of women older than 35 years did not participate in prenatal testing or ultrasound. Ultrasound detected Down syndrome with a sensitivity of 59% (95% confidence interval: 45–72%), a false‐positive rate of 10.6% (9.4–11.8%) and a positive predictor value of 1 in 9. The likelihood of having normal karyotype if the sonogram was normal was 0.46 (0.31–0.61). In women older than 35 years, a normal second trimester sonogram reduces the risk of Down syndrome by more than 50%. At least 17% of women older than 35 years do not participate in prenatal testing or ultrasound.