Mitogenic effect of fibroblast growth factor on early passage cultures of human and murine fibroblasts.

Fibroblast growth factor (FGF), a polypeptide that has been shown to stimulate division in 3T3 cells, was tested for mitogenic effects on diploid, early-passage cells from human and murine sources. The quantitative assay of [3H]thymidine incorporation into acid-insoluble material showed that FGF at low concentrations (10 minus 9 M) was more effective than additional serum for provoking the initiation of DNA synthesis in human foreskin fibroblasts or mouse fibroblasts maintained in 5 or 10% serum, respectively. The growth of the human fibroblasts was twice as fast in the presence of FGF plus 10% calf serum as it was in the presence of 10% calf serum or 20% fetal calf serum alone. The addition of FGF to primary cultures of mouse fibroblasts in 0.4% serum resulted in a twofold increase in cell number compared to controls. In contrast to results obtained with 3T3 cells, neither insulin nor a glucocorticoid potentiated the effects of FGF on either human or mouse cells.

Effect of fibroblast growth factor on the division and fusion of bovine myoblasts.

The effect of fibroblast growth factor (FGF) on the rate of proliferation and fusion of bovine myoblast has been examined. Addition to the cultures of 0.1 mug-1 mug/ml of FGF stimulates the rate of proliferation and delays the fusion of primary cultures of bovine myoblasts cultured in 10% serum. Final cell densities reached in the presence of 0.1 mug/ml of FGF were fivefold higher than in controls; with 1 mug/ml, they were 10-fold higher. Increases in cell density were paralleled by increases in acetylcholine receptor sites as measured by the binding of 125I-alpha-bungarotoxin. Both fusion and the appearance of acetylcholine receptor sites were delayed in the presence of FGF. Growth hormone, insulin and testosterone, which have been reported to be mitogenic for rat and chick embryo myoblasts, did not have significant effects on DNA synthesis in bovine myoblasts when compared to the FGF. Conversely, FGF did not stimulate the proliferation of chick embryo myoblasts, indicating that it is not active in all vertebrate species.

Effects of fibroblast growth factor and epidermal growth factor on the rate of growth of amniotic fluid-derived cells.

Primary cultures of cells derived from human and bovine amniotic fluid were cultivated in Dulbecco's modified Eagles medium with 20% fetal calf serum. Whereas increased concentrations of fetal calf or other types of serum bring about no further mitogenic response, the rate of growth of these cells was nevertheless sharply increased when 100 ng/ml of FGF was added to the culture media. The FGF induced mitogenic effect was statistically significant. EGF at 100 ng/ml had a less pronounced effect which, when analyzed statistically, was not significant. Amniotic fluid-derived cells are used for the prenatal detection of genetic disorders. The use of FGF to increase the rate of growth of these cells should reduce the time required between amniocentesis and diagnosis.

Epidemiological surveillance in Peace Corps Volunteers: a model for monitoring health in temporary residents of developing countries.

In 1985, the US Peace Corps developed a computerized epidemiological surveillance system to monitor health trends in over 5500 Peace Corps Volunteers working in development projects in 62 countries worldwide. Data on 31 health conditions and events are collected monthly from each country; quarterly and annual incidence rates are then calculated, and the analysed data are distributed. In 1987, the most commonly reported health problems were diarrhoea (unclassified), 48 cases per 100 volunteers per year; amoebiasis, 24 per 100 volunteers per year; injuries, 20 per 100 volunteers per year; bacterial skin infections, 19 per 100 volunteers per year; and giardiasis 17 per 100 volunteers per year. Tracking each of these common problems, as well as other selected health conditions, guides design of more specific studies and disease control efforts. Health problems with very low rates (less than 1.0/100 volunteers/year) include hepatitis, schistosomiasis, non-falciparum malaria, and filariasis. The epidemiological surveillance system provides the health data needed to plan, implement, and evaluate health programmes for Peace Corps Volunteers, and provides a model for surveillance in other groups of temporary and permanent residents of developing countries.

Epidemiological considerations of sexually transmitted diseases in underserved populations.

Although unexplained declines in the number of bacterial sexually transmitted diseases (STDs) are currently being documented on a national level, increasing rates among minority populations and among adolescents in general, present challenges for STD prevention and control. By contrast, little evidence has been presented to suggest declines in rates of incident viral STDs in any population. Unique approaches to prevention and control based on the epidemiological heterogenicity of STDs are discussed.

High rate of bacterial vaginosis among women with intrauterine devices in Manado, Indonesia.

Recent research reported that bacterial vaginosis (BV) might enhance the acquisition and transmission of HIV. BV is also associated with an increased risk of pelvic inflammatory disease, a disease also associated with intrauterine device (IUD) insertion. To measure the magnitude of this problem, we conducted a prevalence survey of BV and sexually transmitted diseases (STDs; defined as current infections with Neisseria gonorrhoeae, Chlamydia trachomatis, and/or Trichomonas vaginalis) among all patients attending a family planning clinic in Manado from May to July 1999. BV was diagnosed by Gram stain using Nugent's criteria and vaginal trichomoniasis by wet mount or culture. Cervical infections with C. trachomatis and N. gonorrhoeae were diagnosed by DNA probe. Of 357 patients, 116 (32.5%) had BV, 83 (23.3%) had trichomoniasis, 9 (2.5%) had chlamydia, and 8 (2.2%) had gonorrhea. The prevalence of STD was similar among users of all types of contraception. However, BV was more common among IUD users (47.2%) than among non-IUD users (29.9%). This association persisted after controlling for age, education, ever had douching, and any STD (odds ratio 2.0, 95% CI 1.1-3.8). BV was also associated with STD (41.3% in women with STD vs. 29.4% in women without). This association remained significant after adjusting for age, education, ever had douching, and IUD use (odds ratio 1.7, 95% CI 1.1-2.9). Because we found that BV was associated with IUDs and that other studies reported that both BV and IUDs were associated with pelvic inflammatory disease, a Gram stain evaluation of BV may be considered prior to IUD insertion

High rates of sexually transmitted diseases among male transvestites in Jakarta, Indonesia.

Many male transvestites (waria) in Jakarta, Indonesia engage in unprotected receptive anal and oral intercourse with homosexual and bisexual men for pay. Although this behaviour clearly puts them at risk of sexually transmitted diseases (STDs), including HIV infection, little is known about the prevalence of STD among them. To learn the STD prevalence and its risk factors, we conducted an STD prevalence survey among waria in North Jakarta, Indonesia. From August to December 1999 we offered screening for rectal and pharyngeal infections with Neisseria gonorrhoeae (Ng), Chlamydia trachomatis (Ct) by DNA probe (GenProbe PACE 2) and for Treponema pallidum (Tp) by non-treponemal and treponemal serological tests. Of 296 participants (median age 28 years), 93% reported having been paid for sex. A total of 96% reported having had oral sex (median five times/week) and/or anal sex (median three times/week) in the last week. Ng was found in the rectum of 12.8% and the pharynx of 4.2%; Ct was found in 3.8% and 2.4%, respectively. A total of 43.6% had reactive non-treponemal and treponemal tests. Of the 129 with positive treponemal tests, 42.6% had non-treponemal test titres greater than 1:8. In the logistic regression model, waria who were younger (< or =25 years old) had a significantly 3.5 times risk of Ng and/or Ct infections than older waria (>25 years old). Because only 12% of waria stated that they consistently used condoms during any sex act, it is important to warn them that STD/HIV transmission can occur with either anal or oral sex and that the risk of either anal or oral transmission can be reduced by condom use. In addition, high rates of asymptomatic syphilis and rectal gonorrhoea warrant a periodic screening and treatment for these infections in this population. Because waria have the highest rates of HIV and their clients consist of homosexual and bisexual men, successful prevention efforts in waria could help curb the spread of the epidemic.

The impact of sexually transmitted diseases on minority populations.

Sexually transmitted diseases (STD) are more prevalent among some minority populations in the United States than they are among the white majority. Primary and secondary syphilis occurs 45 times as often among non-Hispanic blacks as among non-Hispanic whites and 13 times as often among Hispanics as among non-Hispanic whites, according to morbidity reports received in 1988 by the Centers for Disease Control. Gonorrhea is reported more commonly among some minorities, with 1988 rates per 100,000 population being 54 for whites, 1,801 for blacks, and 201 for Hispanics. The reasons for the higher incidence of STD among some minorities are unknown. Data on racial differences in behavior and disease susceptibility are meager and do not account for the observed differences. Poverty, which is more common among some minorities than among the white majority, is closely associated with the prevalence of STD and may be a link between membership in a minority population and an increased risk.

Treating uncomplicated Neisseria gonorrhoeae infections: is the anatomic site of infection important?

BACKGROUND: The efficacy of new antimicrobial regimens against Neisseria gonorrhoeae infection of sites other than the urethra and cervix is rarely adequately assessed. GOAL OF THIS STUDY: To learn whether modern antigonococcal agents eradicate infections at some mucosal sites less reliably than at others. STUDY DESIGN: This was a systematic review of published therapeutic trials of various antimicrobial regimens for the biological cure of uncomplicated mucosal Neisseria gonorrhoeae infections. Data were aggregated by treatment regimen and the cure rates were calculated by site of infection. RESULTS: Of 16,737 infections, 96.4% were cured--female urethra, 98.4%; male urethra, 96.4%; cervix, 98.0%; female pharynx, 83.7%; male pharynx, 79.2%; female rectum, 97.9%; and male rectum, 95.3%. The differences between the cure rates at the pharynx and at all other sites were statistically significant in the crude analysis and after stratifying by treatment regimen. CONCLUSION: Modern antigonococcal regimens highly effective against infection of the urethra are highly effective at the cervix and rectum as well, but pharyngeal infections are more difficult to cure.

Drugs of choice for the treatment of uncomplicated gonococcal infections.

Resistance of Neisseria gonorrhoeae to antimicrobial agents continues to spread and intensify. Choosing an antimicrobial regimen requires knowledge of the comparative efficacy of candidate regimens, as delineated in properly conducted clinical trials; their activity against N. gonorrhoeae in vitro; and their pharmacokinetics and toxicity. We tabulated the results of trials of single-dose antimicrobial therapy for uncomplicated gonococcal infection published after 1980. Thirty regimens comprising 21 antimicrobial drugs have been shown to be highly effective for rectal and urogenital infections; the agents involved are cefixime, cefodizime, cefotaxime, cefoxitin, ceftizoxime, ceftriaxone, cefuroxime, cefuroxime axetil, ciprofloxacin, fleroxacin, norfloxacin, ofloxacin, pefloxacin, temafloxacin, azithromycin, aztreonam, netilmicin, rifampin plus erythromycin stearate, sisomicin, and spectinomycin. Few regimens have been shown to be highly effective against pharyngeal infections. Among those antimicrobial agents available for the treatment of uncomplicated gonococcal infections in the United States, ceftriaxone (125 mg), cefixime (400 mg), ciprofloxacin (500 mg), and ofloxacin (400 mg) appear to offer the best balance of proven efficacy and safety.

The spread of chloroquine-resistant malaria in Africa. Implications for travelers.

Spreading from 2 countries in 1978 to at least 29 in 1988, chloroquine-resistant Plasmodium falciparum malaria has become a significant concern for travelers to Africa. The spread of chloroquine resistance has been documented by sporadic case reports and by isolated population surveys, which do not always completely reflect the risk of infection for travelers using chloroquine prophylaxis. Surveillance of Peace Corps volunteers in West Africa indicates that as of January 1, 1989, P falciparum malaria resistant to chloroquine prophylaxis had spread as far west as Liberia, with only limited risk in Sierra Leone and to the north and west of Sierra Leone. Monitoring the incidence of malaria in highly exposed expatriates provides early warning of the emergence of drug-resistant P falciparum malaria and can provide data to guide recommendations for travelers.

Stimulation of division of sparse and confluent 3T3 cell populations by a fibroblast growth factor, dexamethasone, and insulin.

The stimulation of division of Balb/c 3T3 mouse fibroblasts by fibroblast growth factor alone and in combination with insulin and a glucocorticoid (dexamethasone) has been investigated. Fibroblast growth factor stimulates DNA synthesis in sparse, quiescent cultures maintained in a low serum concentration, but does not support more than two division cycles. In the presence of dexamethasone, the growth factor supports continuous division cycles. The addition of insulin significantly augments the response to fibroblast growth factor alone and slightly augments the response to growth factor plus dexamethasone. Fibroblast growth factor stimulates the division of confluent, quiescent cultures grown in 10% serum. When growth factor plus dexamethasone is added to such cultures, "contact inhibition" is overcome.

Therapy for gonococcal infections: options in 1989.

The choice of therapy for Neisseria gonorrhoeae infections is complicated by antibiotic resistance and by the varying efficacy of some antibiotics at different anatomic sites of infection. Ceftriaxone (a single intramuscular dose of 250 mg) is a simple, effective, and generally well-tolerated choice for uncomplicated N. gonorrhoeae infection at all anatomic sites. Alternatives include single-dose oral regimens of ciprofloxacin, norfloxacin, and cefuroxime axetil as well as single-dose intramuscular regimens of spectinomycin, ceftizoxime, and cefotaxime. The addition of doxycycline (100 mg orally twice a day for 7 days) is recommended for presumptive treatment of chlamydial coinfection. Tetracyclines should not be used as sole therapy for gonococcal infection because of gonococcal resistance.

Control of proliferation of bovine vascular endothelial cells.

The effects of Fibroblast Growth Factor (FGF) and Epidermal Growth Factor (EGF) on the proliferation of bovine vascular endothelial cells has been examined. FGF induces the initiation of DNA synthesis and cell proliferation in cloned endothelial cells of fetal and adult origin at concentrations as low as 1 ng/ml and is saturating at 50 ng/ml. EGF had no effect over the same range of concentrations. The mitogenic effect of FGF is blocked by a crude extract of cartilage. Platelet extract is also mitogenic for vascular endothelial cells although to a lesser extent than the purified FGF. In contrast to vascular endothelial cells, both EGF and FGF are mitogenic for vascular smooth muscle cells although EGF is less mitogenic than FGF at 100 ng/ml. The mitogenic effect of EGF and FGF on vascular smooth muscle is not blocked by the addition of a crude extract of cartilage, thus demonstrating the specificity of the chalone like effect of cartilage crude extract for endothelial cells.

Sentinel surveillance for antimicrobial resistance in Neisseria gonorrhoeae--United States, 1988-1991. The Gonococcal Isolate Surveillance Project Study Group.

PROBLEM/CONDITION: The prevalence of antimicrobial resistance in Neisseria gonorrhoeae in the United States has been increasing since the mid-1970s. DESCRIPTION OF SYSTEM: The Gonococcal Isolate Surveillance Project (GISP) was established in 1986 to monitor trends of antimicrobial resistance in N. gonorrhoeae. GISP is a sentinel surveillance system consisting of 26 publicly funded sexually transmitted disease clinics and five regional laboratories. At each clinic, urethral isolates are obtained from the first 20 men diagnosed with gonorrhea each month; these isolates are shipped to one of the regional laboratories, where the susceptibilities of the organisms to a panel of antibiotics are determined. REPORTING PERIOD COVERED: This report describes the results of surveillance for antimicrobial resistance in N. gonorrhoeae from January 1991 through December 1991. These results are compared with data obtained from January 1988 through December 1990. RESULTS AND INTERPRETATION: In the 1991 GISP sample, 32.4% of isolates were resistant to penicillin or tetracycline. The proportions of isolates with high-level, plasmid-mediated resistance to penicillin, tetracycline, or both drugs have increased significantly (p < 0.001) in the GISP sample during 1988-1991. No documented clinical treatment failures have been related to decreased susceptibility of N. gonorrhoeae to either ceftriaxone or ciprofloxacin, which belong to the classes of antibiotics currently recommended for gonococcal therapy. ACTION TAKEN: Because of the demonstrated ability of N. gonorrhoeae to develop resistance to antimicrobial agents, surveillance to guide therapy recommendations will be continued.

Increase in condom sales following AIDS education and publicity, United States.

Data from a national probability sample of drug stores show that condom sales rose from 240 million annually in 1986 to 299 million in 1988. The greatest increase occurred in 1987 after the Surgeon General's report on AIDS was released. Sales of latex condoms with spermicide rose 116 percent. Sales of other types of condoms increased less. These data suggest that Americans are using more condoms and probably more effective condoms in response to AIDS education.

Routine hepatitis B vaccination in a clinic for sexually transmitted diseases.

Patients were assigned to one of two vaccine schedules to assess the feasibility of vaccinating a sexually transmitted disease clinic population against hepatitis B virus. Of 1386 patients entering an inner-city clinic between June and July 1990, 611 (44%) accepted a first dose of vaccine. Twenty-one percent of all susceptible patients received at least two doses of vaccine. Annualizing these findings shows that an ongoing program could prevent 636 hepatitis B virus infections per year. Although a significant proportion of sexually transmitted disease clinic patients can be successfully vaccinated, strategies for preventing hepatitis B virus infections in this high-risk population must consider patient behavior as well as vaccine efficacy.

Gonorrhea in the United States, 1981-1996. Demographic and geographic trends.

OBJECTIVE: To describe demographic and geographic trends in gonorrhea incidence in the United States from 1981 through 1996. STUDY DESIGN: We analyzed aggregate gonorrhea cases reported to the Centers for Disease Control and Prevention by the 50 states, District of Columbia, and 63 large cities. Annual incidence rates (cases/100,000 persons) were calculated. RESULTS: Between 1981 and 1996, the incidence of reported gonorrhea decreased 71.3%, from 431.5 to 124.0 cases/100,000. However, rates among blacks were 35 times higher than rates among whites in 1996 (684.6 versus 19.4) compared with 11 times higher in 1981 (1,894.3 versus 164.3). Among women of all races, 15 to 19 year olds had the highest rates (716.6 in 1996), whereas among men, 20 to 24 year olds had the highest rates (512.9 in 1996). Southern states had higher rates than other regions. CONCLUSIONS: Large segments of the population, including adolescents, young adults, and blacks, continue to have high rates of gonococcal infection; prevention programs and health care providers should address the needs of these groups.