Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia.

CONTEXT: Human papillomavirus (HPV) infection is believed to be the central cause of cervical cancer, although most of the epidemiological evidence has come from retrospective, case-control studies, which do not provide information on the dynamics of cumulative or persistent exposure to HPV infection. OBJECTIVE: To assess the risks of cervical neoplasia related to prior persistent HPV infections. DESIGN AND SETTING: Longitudinal study of the natural history of HPV infection and cervical neoplasia in women residing in the city of São Paulo, Brazil, which was conducted between November 1993 and March 1997 and involved repeated measurements of HPV and lesions with follow-up until June 2000. PARTICIPANTS: A total of 1611 women with no cytological lesions at enrollment and HPV test results available from the first 2 visits. MAIN OUTCOME MEASURE: Cervical specimens taken for Papanicolaou cytology and HPV testing every 4 months in the first year and twice yearly thereafter. Incident cervical cancer precursor lesions ascertained by expert review of all cytology smears. RESULTS: The incidence rate of squamous intraepithelial lesions (SILs) was 0.73 per 1000 women-months (95% confidence interval [CI], 0.5-0.9) among women free of HPV at the 2 initial visits and 8.68 (95% CI, 2.3-15.1) among women with HPV type 16 or 18 infections persisting over both visits. Relative to those negative for HPV oncogenic types at both initial visits, the relative risk (RR) of incident SIL was 10.19 (95% CI, 5.9-17.6) for persistent infections with any known oncogenic HPV types. The equivalent RR of incident high-grade SIL was 11.67 (95% CI, 4.1-33.3). The RRs of lesions were considerably higher for persistent infections with HPV type 16 or 18. CONCLUSION: A strong relationship exists between persistent HPV infections and SIL incidence, particularly for HPV types 16 and 18.

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) inhibits the binding activity of T4 endonuclease V to UV-damaged DNA.

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is a mutagen/carcinogen derived from cooked foods which enhances the induction of mutations and chromosome aberrations by UV without microsomal activation. These co-mutagenic effects are considered to arise from inhibition of DNA excision repair at the incision step. However, the inhibition mechanism has not been clarified. In this study we show, using agarose gel electrophoresis, that Trp-P-1 inhibits incision by T4 endonuclease V, which cleaves DNA at the site of cyclobutane dimers. Trp-P-1 also inhibits the binding of this enzyme to UV-damaged DNA in a gel shift assay. In addition, the results of DNA unwinding assay with topoisomerase I suggest that Trp-P-1 intercalates into DNA molecules. The known intercalators ethidium bromide and acriflavine demonstrate similar effects in these experiments. However, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which showed no co-mutagenic effects in our previous study, does not demonstrate such effects. These results suggest that Trp-P-1 changes DNA conformation by intercalation, causing inhibition of binding of repair enzymes to UV-damaged DNA, and this in turn leads to inhibition of DNA excision repair and to co-mutagenic effects.

[Acute nongonococcal epididymitis--pharmacological and therapeutic aspects of levofloxacin].

We performed basic and clinical studies on the effects of a new oral quinolone derivative, levofloxacin (LVFX, Code No. DR 3355) which is an optical l-isomer of ofloxacin, in acute epididymitis. LVFX was administered in a dose of 200 mg to prostatic cancer patients 2 hours before operation. The mean concentration of LVFX in the tissues of testis and epididymis were 4.73 micrograms/g and 313-3.6 micrograms/g, respectively. Tissue/Serum ratios were 1.63 and 1.16-1.32, respectively. LVFX was administered in a dose of 100 mg three times daily for 13 days to healthy male volunteers. Semen and blood samples were taken 2 hrs after 7th and last day of administration. The concentration of LVFX in semen were 1.19 micrograms/ml (7th day) and 1.32 micrograms/ml (13th day). Semen/serum ratios were 1.12 and 1.26, respectively. No affection of LVFX on the sperm was observed. Antimicrobial activity of LVFX to C. trachomatis showed good MICs of 0.25-1.0 micrograms/ml. LVFX was administered in a dose of 100 mg two or three times daily for 14 days to 23 patients with acute epididymitis. The overall efficacy rate based on a criteria for acute epididymitis showed 100% (excellent: 16, good: 4, 20/20). A better efficacy rate was obtained on the 14th day than 7th day. No subjective or objective adverse reactions were observed.

[Bacteriological and clinical studies on fleroxacin in male gonococcal urethritis].

We performed basic and clinical studies on the effects of a new oral antimicrobial agent, fleroxacin (FLRX), a new quinolone derivative in male gonococcal urethritis. The antibacterial activity of FLRX against clinical strains of Neisseria gonorrhoeae was roughly comparable to that of norfloxacin and ofloxacin. FLRX was administered to 58 males with gonococcal urethritis. Two different schedules of administration were adopted. One was a single-dose of 300 mg given orally (17 cases) and the other was the oral administration of 200 mg once a day for 3 to 10 days (41 cases). Clinical evaluation was made according to the criteria of the Japanese UTI Committee. The overall efficacy rate was 98% (49/50). For complications of Chlamydia trachomatis (11 cases), the efficacy rate was 90.9% (10/11). No subjective or objective adverse reaction occurred.

[Application of parenteral cephradine in urinary tract infections (author's transl)].

A new antibiotic cephradine was administered intravenously for 3 approximately 7 days at daily doses of 1.0 approximately 2.0 g to 56 patients, including 39 cases of acute urinary tract infections, 13 of chronic urinary tract infections and 4 for postoperative prophylaxis. Of 39 cases with acute urinary infections, definite response was seen in 35 cases and no definite response in 4 cases. Of 13 cases with chronic urinary tract infections, definite response was seen in 7 cases and no definite response in 6 cases. Good results were obtained clinically in 4 cases for prophylaxis of postoperative infections. No side effect was observed with cephradine with cephradine throughout the experiment.