Reduced chlamydial infection and gonorrhea among commercial sex workers in Fukuoka City, Japan.

BACKGROUND: Until recently, epidemiologic studies of sexually transmitted diseases (STDs), including human immunodeficiency virus type-1 (HIV-1) infection, among Japanese female commercial sex workers and their patterns of condom use have been rare. We investigated trends in STDs among female commercial sex workers and their condom use patterns in Fukuoka, Japan, from 1990 through 1995. METHODS: The study group consisted of 1218 female commercial sex workers who attended an STD clinic to undergo screening for major STDs including chlamydial infection, gonorrhea and HIV-1 infection from 1990 through 1995. Endocervical smear specimens were taken from the women to detect Chlamydia trachomatis and Neisseria gonorrhoeae, and blood samples were obtained for the serologic diagnosis of HIV-1. Also, the commercial sex workers were interviewed concerning their condom use patterns. RESULTS: The annual infection and detection rates of C. trachomatis declined significantly from 58.1% in 1990 to 46.2% in 1995 and from 16.3% in 1990 to 10.0% in 1995, respectively, while the annual infection and detection rates of N. gonorrhoeae also declined significantly from 13.2% in 1990 to 3.5% in 1995 and from 1.5% in 1990 to 0.4% in 1995, respectively. None were found to be seropositive for HIV-1 during the 6-year period. The proportion of commercial sex workers using condoms significantly increased during 1992-1993 and 1994-1995 periods, as compared with the 1990-1991 period. CONCLUSION: Reductions in the prevalence of major STDs among female commercial sex workers may be related to an increase in the frequency of condom use.

Effect of urine component on leukocyte chemiluminescence response.

In the urine, the function of polymorphonuclear leukocytes (PMNs) is thought to be impaired because of the high osmolality and low pH along with a high concentration of inorganic salts. We investigated the effect of the properties of urine and its components on the chemiluminescence (CL) response of PMNs. This was helped by using an artificial urine. The CL response was measured by automatic luminometer following stimulation of phorbol myristate acetate. We found the CL response of PMNs to be significantly suppressed at a pH of 6 or 5, but not suppressed at a pH of 7 or 8. The CL response was significantly reduced when the osmolality was increased to 580 or 800 mOsm/kg H2O by the addition of urea as compared to the response in the standard artificial urine at an osmolality of 425 mOsm/kg H2O. A change in the osmolality by the addition of mannitol only minimally influenced the CL responses. In addition, the CL response was significantly impaired by both low and high concentrations of sodium at 12 and 300 mEq/L as compared to 77.5 mEq/L in the standard artificial urine. Potassium significantly reduced the CL response in a concentration-dependent manner in the range of from 4 to 31 mEq/L as compared to 52.3 mEq/L in the standard artificial urine. A high concentration of calcium at 8.1 or 9.9 mg/dL reduced CL response as compared to 3.9 mg/dL, whereas CL response was not reduced by the change in the concentration of magnesium. A high concentration of creatinine significantly reduced the CL response as compared to the standard artificial urine. We conclude that the function of PMNs in urine is reduced mainly by urine pH, concentration of urea, sodium, potassium, and creatinine. We suggest that reversal of these change in urine may restore functions of PMNs to clear bacteria in patients with urinary tract infections.

Reduced clinical efficacy of pazufloxacin against gonorrhea due to high prevalence of quinolone-resistant isolates with the GyrA mutation. The Pazufloxacin STD Group.

Forty-two men with gonococcal urethritis were treated with an oral dosage of 200 mg of pazufloxacin, a new fluoroquinolone, three times daily for 3 days. Only 28 of the 42 men (66.7%) had negative culture results for Neisseria gonorrhoeae during follow-up. Of the 42 isolates, 41 could be recultured for antibiotic susceptibility testing and DNA sequencing. In 26 of the 41 isolates (63.4%), GyrA mutations with or without ParC mutations were identified. Among the 26 isolates, 23 contained a single GyrA mutation, 1 contained two GyrA mutations, and 2 contained three mutations including double GyrA and single ParC mutations. A single Ser-91-to-Phe mutation, which was detected in 14 of the 26 isolates, was the most common GyrA mutation, followed by an Ala-75 to Ser mutation and an Asp-95 to Asn or Gly mutation in GyrA. All three isolates with two or three mutations contained the Ser-91-to-Phe GyrA mutation. Eleven of the 14 isolates with the single Ser-91-to-Phe mutation within GyrA and all 3 isolates with two or three mutations persisted after pazufloxacin treatment. On the other hand, all 15 wild-type and 9 mutant isolates with a substitution at codon Ala-75 or Asp-95 were eradicated. The mean MIC of pazufloxacin for mutants with the single Ser-91-to-Phe mutation in GyrA was 66-fold higher than that for the wild type. The results obtained in this study suggest that a high prevalence of fluoroquinolone-resistant gonococcal isolates with the Ser-91-to-Phe mutation in GyrA reduced the efficacy of pazufloxacin as treatment for gonococcal urethritis.

Preventive effect of dapsone on renal scarring following mannose-sensitive piliated bacterial infection.

Renal scarring has been thought to occur in the later stages of chronic pyelonephritis. We previously reported that mannose-sensitive (MS) piliated bacteria promoted renal scarring, which was prevented by antioxidants. The preventive effect of diaphenylsulfone (dapsone), which has a scavenging activity on active oxygen species, on renal scarring was examined. Female Sprague-Dawley rats were inoculated with clinical isolates of Serratia marcescens which had both MS and mannose-resistant pili or with recombinant strains which had MS pili on their surface; they were then administered 20 mg/kg of dapsone or not. Dapsone significantly suppressed scarring following infection of the kidney. The bacterial counts in the kidneys were not different in dapsone-treated and nontreated rats. We conclude that dapsone is effective in preventing renal scarring, and it is suggested that the clinical use of this drug may prevent renal scar formation following pyelonephritis.

Olfactory evoked potential produced by electrical stimulation of the human olfactory mucosa.

Most physiological studies of the human olfactory system have concentrated on the cortical level; the olfactory bulbar level has been studied rarely. We attempted to stimulate the human olfactory mucosa by electrical pulse to detect the bulbar potentials. Electrical stimulation (2 mA, 0.5 ms) of the human olfactory mucosa evoked a change in potential recorded from the frontal sector of the head. A negative peak of the evoked potential that occurred at 19.4 ms (grand means, n = 5) after stimulation was the clearest. The highest amplitude of the potential was recorded from the frontal sector of the head on the stimulated side. Our findings were similar to the experimental results obtained from the olfactory bulbs of animals. This evoked potential was considered to be the human olfactory bulbar potential. When the subjects were stimulated by applying electricity to the olfactory mucosa, no sensation of smell occurred even though evoked potentials were recorded. Evoked potentials were recorded only when the stimulating electrode was located in the olfactory cleft. When the stimulating electrode was outside the olfactory cleft, the stimulation caused pain. The trigeminal nerve seemed to be stimulated by electricity. Olfactory evoked potentials produced by the electrical stimulation of the human olfactory mucosa should aid the research on human olfactory physiology, and may be applicable to clinical tests of olfactory dysfunction.

Renal scarring by mannose-sensitive adhesin of Escherichia coli type 1 pili.

Most Escherichia coli isolates from patients with pyelonephritis possess both pap (mannose-resistant) pili and type 1 (mannose-sensitive) pili. In the experimental pyelonephritis model of rats, the mannose-sensitive-piliated strain caused severe renal scarring, whereas the mannose-resistant or nonpiliated strain did not. Type 1 pili consist of several subunits; one major subunit and other minor subunits. One of the minor subunits, adhesin, is responsible for mannose-sensitive adhesion to eukaryotic cells. The role of adhesin was examined in scar formation after infection with a newly constructed adhesin-deficient mutant which has pilus structure but cannot agglutinate guinea pig erythrocytes. A mutant plasmid, pYMZ84, containing a deletion in the adhesin gene of type 1 pili, failed to agglutinate guinea pig erythrocytes even though the bacteria expressed pili morphologically indistinguishable from those produced by plasmid pSH2, carrying the intact genes for the type 1 pili. E. coli harboring pYMZ84 caused negligible or minimal renal scarring, whereas E. coli harboring pSH2 caused severe renal scarring in rats. These data suggest that the mannose-sensitive adhesin of type 1 pili stimulates renal scarring.

Chemiluminescence response of whole blood in patients undergoing urological operations.

Polymorphonuclear leukocytes (PMNs) are one of the most important components of the defence mechanisms against bacterial infection. The functions of PMNs are believed to be impaired in patients during the perioperative period. Bactericidal function of PMNs was investigated together with the luminol-dependent chemiluminescence (CL) reaction of whole blood in 23 patients, 12 undergoing open surgery and 11 undergoing endoscopic surgery. Blood samples were collected one day before surgery (day -1) and 2 hours (day 0), 24 hours (day 1) and 7 days (day 7) after surgery. Counts of whole white blood cells (WBCs), PMNs and lymphocytes were not different between the two surgery groups. CL responses in the open surgery group were increased on days 0, 1 and 7. In the endoscopic surgery group, CL response was increased on day 1, but not on day 0 or day 7. These results suggest that the PMN function during the perioperative period was not impaired, but increased just after surgery, mainly due to an increasing number of WBC caused by the surgical intervention.

Prevention of catheter-associated urinary tract infection by meatal disinfection.

The incidence of catheter-associated urinary tract infections (UTIs) becomes higher with prolongation of the indwelling period of a catheter. As to the entry of bacteria, ascending UTIs have now attracted attention. In the present study. the metal area was examined bacteriologically and the possibility to use antiseptics for blocking the route of developing infections was investigated. The subjects included 72 patients with an indwelling, urethral catheter inserted post-operatively. These patients were divided into three groups treated with once or twice daily application of povidone-iodine or once daily application of povidone-iodine cream. In these groups, the relation between changes in isolation of bacteria from the meatal area and the incidence of UTI was evaluated. It was found that reduction in bacterial count by antisepsis is effective to prevent ascending UTIs. Moreover, once daily application of povidone-iodine was proven to be effective in male patients. The effective antisepsis in females was twice daily application of povidone-iodine.

Trends in sexually transmitted diseases and condom use patterns among commercial sex workers in Fukuoka City, Japan 1990-93.

OBJECTIVE: To investigate trends in sexually transmitted diseases (STDs) among female commercial sex workers and in their condom use patterns during the period from 1990 to 1993 in Fukuoka, Japan. METHODS: The study group consisted of a total of 824 commercial sex workers who attended an STD clinic to undergo screening for STDs including chlamydia, gonorrhoea, syphilis, hepatitis B and HIV-1 infection during the period from 1990 to 1993. For detection of Chlamydia trachomatis and Neisseria gonorrhoeae, endocervical smear specimens were taken from the women. Blood samples were obtained for serological diagnosis of syphilis, hepatitis B and HIV-1. Commercial sex workers who visited the clinic during the period from November to December of 1993 were interviewed concerning past (1990 and 1991) and recent (1992 and 1993) condom use patterns. RESULTS: The annual detection rates of C trachomatis and N gonorrhoeae declined significantly from 16.3% in 1990 to 12.2% in 1993 (P < 0.0001) and from 1.5% in 1990 to 0.8% in 1993 (P = 0.0096), respectively. There was a remarkable reduction in the annual syphilis infection rate, from 7.5% in 1990 to 0.5% in 1993 (P = 0.0011). The positive rate for the hepatitis B surface antigen in the women ranged from only 0.6% to 1.9% and none were found to be positive for HIV-1 during the 4-year period. During the same period, there was a significant increase in the proportion of commercial sex workers always using condoms from 6.3% in 1990-91 to 25.3% in 1992-93 (P = 0.0023). CONCLUSION: The prevalences of chlamydia, gonorrhoea, and syphilis infections decreased significantly among commercial sex workers in Fukuoka from 1990 through 1993, and no commercial sex workers were HIV-1 seropositive. The reductions in the prevalence of major STDs may be related to the increased use of condoms.

PIP: A survey of commercial sex workers in Fukuoka City, Japan, during 1990-93 revealed significant declines in the prevalence of chlamydia, gonorrhea, and syphilis during the study period, presumably as a result of increased condom use. The study group consisted of 824 commercial sex workers who attended a sexually transmitted disease (STD) clinic in Fukuoka from 1990 to 1993 for voluntary STD check-ups. The annual Chlamydia trachomatis detection rate declined from 16.3% in 1990 to 12.2% in 1993; the annual detection rate for Neisseria gonorrhoeae fell from 1.5% to 0.8%, while that for syphilis dropped from 7.5% to 0.5%. None of the 791 women screened for human immunodeficiency virus was seropositive. In addition, a subsample of 79 commercial sex workers were interviewed about their condom use. The proportion of sex workers always using condoms rose from 6.3% in 1990 to 25.3% in 1993; in this period, never use of condoms decreased from 45.6% to 5.1%.

Distribution of a methicillin-resistance gene in urinary isolates of methicillin-resistant staphylococci examined by enzymatic detection of the polymerase chain reaction.

We tried to examine the susceptibility to various antimicrobial agents and to detect the mec A gene using enzymatic detection of the polymerase chain reaction in methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA) and Staphylococcus epidermidis isolated from patients with complicated urinary tract infections (UTIs). All the strains of MRSA and MSSA showed a low sensitivity to imipenem (IPM), ceftazidime (CAZ), flomoxef (FMOX), amikacin (AMK), ciprofloxacin (CPFX) and ofloxacin (OFLX). Although all the strains of MRSA had the mec A gene, none of the MSSA strains had it. 74% of S. epidermidis had the mec A gene and strains resistant to methicillin were seen in 72% of them. The mec A-positive S. epidermidis showed a lower susceptibility to IPM, CAZ, FMOX, AMK, CPFX and OFLX than the mec A-negative strains. These results suggest that methicillin resistance was due to the mec A gene in MRSA and methicillin-resistant S. epidermidis (MRSE), and that MRSEs were very common among the bacteria causing complicated UTI. When we try to control nosocomial infections due to MRSA, it should also be noted that MRSE can be a reservoir of the mec A gene.

Fleroxacin enhancement of superoxide production by polymorphonuclear leukocytes: the role of protein kinases.

New quinolone (NQ) antimicrobials may influence the functions of polymorphonuclear leukocyes (PMNs). Fleroxacin (FLRX), one of the newer NQs which has a long half-life in blood and a strong bactericidal effect, was examined for its influence on superoxide production by PMNs. Augmentation of superoxide production by PMNs when stimulated with phorbol myristate acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (fMLP) was observed following the addition of 25, 50, 100 and 200 micrograms/ml of FLRX. In addition, the effects of staurosporine and H-7, inhibitors of protein kinase C (PKC), and of genistein, a tyrosine kinase (TK) inhibitor, on FLRX-enhanced superoxide production were examined. Superoxide production augmented by FLRX was diminished by the addition of staurosporine and H-7, when PMNs were stimulated with PMA, and by the addition of genistein, when PMNs were stimulated with fMLP. These results suggest that FLRX augments superoxide production by PMNs through enhancing the activities of phosphorylation by PKC or TK within the signal transduction pathway in PMNs.

Olfactory evoked potentials produced by electrical stimulation of the olfactory mucosa.

We stimulated the olfactory mucosa electrically and elicited evoked potentials in rabbits. A bipolar stimulating electrode was placed on the olfactory region of the nasal mucosa via an anterior naris non-invasively. Evoked potentials were detected from the surface of a head. In most instances they were composed of triphasic negative-positive-negative peaks, the latencies of these peaks were about 25, 40, and 65 ms, respectively. This peak complex seemed to originate in the olfactory bulb. This method is non-invasive and is applicable to studying the olfactory system in animals and also in humans.

Inhibition of chemiluminescence response of human polymorphonuclear leukocytes by three different stimulations in hyperosmotic condition comparable to the renal medulla.

Hyperosmolality in renal medulla inhibits functions of polymorphonuclear leukocyte (PMN) such as phagocytosis, intracellular killing, and superoxide generation. The main factors of hyperosmolality in the renal medulla are thought to be urea and NaCl. We studied the luminol-dependent chemiluminescence (CL) response of PMNs to three different stimulators: phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (FMLP), and opsonized zymosan (OZ). When PMNs were incubated or preincubated with hyperosmotic urea or NaCl solutions, CL responses were significantly reduced following stimulation by each of PMA, FMLP, or OZ. Reduction of CL response was concentration and osmolality dependent in hyperosmotic urea and NaCl solution. These results suggest that respiratory burst and production of active oxygen species of PMNs through three different signal transduction pathways are inhibited in hyperosomotic conditions comparable to the renal medulla.

Ofloxacin and fleroxacin enhance superoxide production in human polymorphonuclear leukocytes by increasing phosphorylation in the signal transduction pathway.

Many antimicrobial agents including new quinolones (NQs) influence the cellular defense mechanisms such as polymorphonuclear leukocytes (PMNs), macrophages and lymphocytes. We examined the effects of NQs on superoxide (SO) production of PMNs following stimulation of phorbol myristate acetate (PMA). Ofloxacin (OFLX) and fleroxacin (FLRX) significantly augmented SO production of PMNs compared to lomefloxacin, sparfloxacin. Staurosporin and H-7, specific inhibitors of protein kinase C of SO production pathway in PMNs, inhibited augmented SO production by OFLX and FLRX in the concentration-dependent manner. NADPH oxidase activity was not influenced by OFLX in cell lysate assay system. These results suggest that OFLX and FLRX augmented PMN function through enhancing protein kinase activity, but not through direct enhancement of NADPH oxidase.

Effect of pili of Serratia marcescens on superoxide production and phagocytosis of human polymorphonuclear leukocytes.

PURPOSE: To determine the role played by superoxide in renal scar formation following renal infection. MATERIALS AND METHODS: The piliation of bacteria was assessed for its capacity to interact with human polymorphonuclear leukocytes (PMNs). Two recombinant strains having either MS or MR pili of Serratia marcescens were constructed. RESULTS: The MS-piliated strain stimulated superoxide production of PMNs twice as much as the MR- or nonpiliated strains did. The MS-piliated strain was more susceptible to phagocytosis than was the MR- or nonpiliated strain. CONCLUSION: These data suggest that the MS-piliated strain stimulates superoxide production of PMNs associated with phagocytosis, which leads to tissue damage in infected organs.

Effect of ebselen on renal scarring in rats following renal infection.

Renal scarring, which occurs following refluxing pyelonephritis, is considered to be involved in the development of reflux nephropathy. Prevention of renal scar formation requires immediate initiation of antimicrobial treatment; treatment delay results in renal scarring. We demonstrate that Ebselen, an antioxidant agent, given at a dose of 15 mg/kg twice a day prevents renal scarring in rats following direct renal parenchymal bacterial inoculation. In addition, using an ascending pyelonephritis model, which clinically resembles refluxing pyelonephritis in humans, we show that when initiation of antimicrobial treatment was delayed, coadministration of Ebselen prevents renal scar formation. These results show that Ebselen is effective in preventing renal scarring and suggest that the clinical use of this drug may prevent renal scar formation following pyelonephritis and progression to reflux nephropathy.