Using the emerging Collaborative Cross to probe the immune system.

The Collaborative Cross (CC) is an emerging panel of recombinant inbred (RI) mouse strains. Each strain is genetically distinct but all descended from the same eight inbred founders. In 66 strains from incipient lines of the CC (pre-CC), as well as the 8 CC founders and some of their F1 offspring, we examined subsets of lymphocytes and antigen-presenting cells. We found significant variation among the founders, with even greater diversity in the pre-CC. Genome-wide association using inferred haplotypes detected highly significant loci controlling B-to-T cell ratio, CD8 T-cell numbers, CD11c and CD23 expression. Comparison of overall strain effects in the CC founders with strain effects at QTL in the pre-CC revealed sharp contrasts in the genetic architecture of two traits with significant loci: variation in CD23 can be explained largely by additive genetics at one locus, whereas variation in B-to-T ratio has a more complex etiology. For CD23, we found a strong QTL whose confidence interval contained the CD23 structural gene Fcer2a. Our data on the pre-CC demonstrate the utility of the CC for studying immunophenotypes and the value of integrating founder, CC and F1 data. The extreme immunophenotypes observed could have pleiotropic effects in other CC experiments.

Relative weight at ages 10 and 16 years and risk of endometriosis: a case-control analysis.

BACKGROUND: Although previous epidemiological studies have shown that women with endometriosis are more likely to be thinner and underweight, it is currently not clear whether this is a true characteristic of women who develop endometriosis or a consequence of their disease and its symptoms. The aim of this study was to investigate the relationship between endometriosis and relative weight in childhood and adolescence, prior to diagnosis. METHODS: This case-control study included 268 Australian women with surgically confirmed moderate to severe endometriosis (cases) and 244 women without endometriosis (controls). Relative weight at ages 10 and 16 years, as recalled and classified ('underweight', 'average weight' and 'overweight') separately by the women themselves and their mothers, was analyzed. RESULTS: Women who reported being overweight at 10 years had an increased risk of endometriosis (OR 2.8; 95% CI 1.1-7.5). Mothers' reports and concordant responses among mother-daughter pairs were consistent with this association. There was no clear evidence of an association between relative weight at 16 years and risk of endometriosis. CONCLUSIONS: These data suggest that being overweight during late childhood is associated with the development of endometriosis; however, the results warrant confirmation in larger study populations.

World association for the advancement of veterinary parasitology (WAAVP) guideline for testing the efficacy of ectoparasiticides for fish.

This guideline is intended to assist in the planning and execution of studies designed to assess the efficacy of ectoparasiticides for fish. It is the first ectoparasite-specific guideline to deal with studies set in the aquatic environment and therefore provides details for the maintenance of environmental standards for finfish. Information is included on a range of pre-clinical study designs as well as clinical studies in commercial/production sites, set within a regulatory framework. It provides information on the study animals, their welfare, husbandry and environmental requirements during the study. The most commonly pathogenic ectoparasites are presented with relevant points regarding life history, host challenge and numeric evaluation. Preparation and presentation of both topical and oral test treatments is provided, together with guidance on data collection and analysis. The guideline provides a quality standard or efficacy studies on finfish, which will assist researchers and regulatory authorities worldwide and contribute to the wider objective of harmonisation of procedures.

Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis.

To define and quantitate histologic changes in the endometrium that best correlate with documented upper genital tract infection (UGTI) and laparoscopically diagnosed acute salpingitis, we studied endometrial biopsy specimens from 69 consecutive patients with clinically suspected acute pelvic inflammatory disease (PID) who underwent microbiological evaluation for UGTI and laparoscopic examination for acute salpingitis. Both UGTI and acute laparoscopically confirmed salpingitis were present in 37 patients (54%), UGTI without salpingitis in 1 (1%), salpingitis without UGTI in 11 (16%), and neither UGTI nor salpingitis in 20 (29%). Chlamydia trachomatis or Neisseria gonorrhoeae UGTI was found in 34 women, Escherichia coli in two patients, Peptococcus magnus in one woman, and with Streptococcus agalactiae in one woman. The following features were correlated both with UGTI and with salpingitis: presence of any neutrophils in the endometrial surface epithelium; neutrophils within gland lumens; dense subepithelial stromal lymphocytic infiltration; any stromal plasma cells; and germinal centers containing transformed lymphocytes. The simultaneous presence of five or more neutrophils per X 400 field in endometrial surface epithelium, together with one or more plasma cell per X 120 field in endometrial stroma, was the best predictor of UGTI plus salpingitis. This combination had a sensitivity of 92% and a specificity of 87% for predicting the diagnosis of both UGTI and laparoscopically confirmable acute salpingitis. Prospective studies are needed to assess the usefulness of these criteria.

Randomized trial of silver nitrate, erythromycin, and no eye prophylaxis for the prevention of conjunctivitis among newborns not at risk for gonococcal ophthalmitis. Eye Prophylaxis Study Group.

OBJECTIVE: To compare the efficacy of commonly used forms of eye prophylaxis for newborns with no prophylaxis in the prevention of nongonococcal conjunctivitis. DESIGN: Randomized doubly masked clinical trial. SETTING: University of Washington Hospital and affiliated clinics, Seattle, between 1985 and 1990. SUBJECTS: The medical records of 8499 women were evaluated for possible participation; 2577 were eligible. Of the 758 enrolled, the infants of 630 were evaluable. INTERVENTION: Comparison of silver nitrate, erythromycin, and no eye prophylaxis given at birth for the prevention of conjunctivitis. MAIN OUTCOME MEASURES: Conjunctivitis during the first 60 days of life and nasolacrimal duct patency in the first 2 days of life. RESULTS: The frequency of impatent tear ducts at the 30- to 48-hour examination did not differ significantly by prophylaxis group. Among the 630 infants randomized and observed, 109 (17%) developed mild conjunctivitis. Sixty-nine (63%) of the cases appeared during the first 2 weeks of life. After 2 months of observation, infants allocated to silver nitrate eye prophylaxis at birth had a 39% lower rate of conjunctivitis (hazard ratio = 0.61, 95% confidence interval = 0.39 to 0.97), and those allocated to erythromycin had a 31% lower rate of conjunctivitis (hazard ratio = 0.69, 95% confidence interval = 0.44 to 1.07), than did those allocated to no prophylaxis. CONCLUSION: Silver nitrate eye prophylaxis caused no sustained deleterious effects and even provided some benefit to infants born to women without Neisseria gonorrhoeae. However, the effect was modest and against microorganisms of low virulence. The results suggest that parental choice of a prophylaxis agent including no prophylaxis is reasonable for women receiving prenatal care and who are screened for sexually transmitted diseases during pregnancy.

Direct fluorescent monoclonal antibody stain for rapid detection of infant Chlamydia trachomatis infections.

A method of direct fluorescent antibody staining for rapid diagnosis of Chlamydia trachomatis infections in infants is described. This method utilized a fluorescein-conjugated species-specific monoclonal antibody to C trachomatis for detecting chlamydial elementary bodies in smears of the conjunctiva, nasopharynx, oropharynx, anus, and vagina. The sensitivity of direct fluorescent antibody staining was compared with isolation of the organisms in McCoy cells. Thirty-nine infants with purulent conjunctivitis were studied. Diagnosis of C trachomatis conjunctivitis was correctly made by smear in all 16 infants when inflamed eyes were sampled. Positive smears were obtained from 12/14 culture-positive and 4/16 culture-negative nasopharyngeal specimens from infants with chlamydial conjunctivitis. All nasopharyngeal cultures and smears from infants with nonchlamydial conjunctivitis were negative. These results indicate that the direct smear test is a sensitive and specific test for diagnosing C trachomatis infection of the eye and nasopharynx in infants, and this test can be completed within one hour of specimen collection.

Delayed appearance of Chlamydia trachomatis infections acquired at birth.

To determine the delay in detectability of Chlamydia trachomatis infections acquired at birth, we serially evaluated 120 infants born vaginally to infected women. Specimens for isolation of Chlamydia were taken from several anatomic sites. Results were analyzed for the age and site of the initial positive culture from each infant. Of 112 infants tested in the first month of life, 22% were culture-positive in the conjunctiva and 25% were positive in the pharynx. Initial positive rectal and vaginal cultures were obtained only in the third and fourth months of life, and all initial vaginal cultures were associated with positive rectal cultures. The latency of C. trachomatis in infants exposed at birth is often more than 1 month and can be longer than 97 days. This latency might be caused by suppression of the growth of the organism by antibodies acquired in utero.

Cefixime vs. cefaclor in the treatment of acute otitis media in children: a randomized, comparative study.

The efficacy of cefixime was compared with that of cefaclor in the treatment of 63 patients with acute otitis media. Patients received either a single dose of cefixime (8 mg/kg/day) or 3 divided doses of cefaclor (40 mg/kg/day). On the basis of otoscopic and tympanometric results at 10 to 14 days after the start of treatment, 28 (97%) of 29 cefixime-treated patients and 25 (78%) of 32 cefaclor-treated patients had resolution of acute otitis media. The clinical cure rate associated with all organisms was 94% for cefixime (16 of 17 isolates) and 68% (13 of 19 isolates) for cefaclor. The cure rate for Streptococcus pneumoniae was 12 of 12 (100%) for cefixime and 7 of 7 (100%) for cefaclor; the cure rate for Haemophilus influenzae (which includes 2 patients with mixed infections) was 3 of 4 (75%) for cefixime and 2 of 7 (29%) for cefaclor. One clinical relapse occurred among 29 cefixime-treated patients; however, at 28 days 9 recurrences were observed. Three of 25 (9%) cefaclor-treated patients failed and 4 (13%) relapsed at 10 to 14 days, an additional 2 (10%) experienced recurrence by Day 28. Eight (28%) cefixime-treated patients experienced adverse events (7 gastrointestinal and 1 diarrhea and rash); 8 (25%) cefaclor-treated patients experienced adverse events (all gastrointestinal). Our data suggest that both at end of therapy and for 14 days thereafter, cefixime given once a day for acute otitis media is clinically equivalent to cefaclor given 3 times a day.

Tobacco smoke as a risk factor for meningococcal disease.

BACKGROUND: Since 1992 the US Pacific Northwest has experienced a substantial increase in the incidence of serogroup B meningococcal disease. The current meningococcal polysaccharide vaccine is poorly immunogenic in young children and does not protect against N. meningitidis serogroup B. Defining alternative approaches to the prevention and control of meningococcal disease is of considerable public health importance. METHODS: We performed a case-control study comparing 129 patients in Oregon and southwest Washington with 274 age- and area-matched controls. We used conditional logistic regression analysis to determine which exposures remained associated with disease after adjusting for other risk factors and confounders and calculated the proportion of disease attributable to modifiable exposures. RESULTS: After adjustment for all other significant exposures identified, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children < 18 years of age [odds ratio (OR), 3.8; 95% confidence interval (CI) 1.6 to 8.9)], with 37% (CI 15 to 65) of all cases in this age group potentially attributable to maternal smoking. Adult patients were more likely than controls to have a chronic underlying illness (OR 10.8, CI 2.7 to 43.3), passive tobacco smoke exposure (OR 2.5, CI 0.9 to 6.9) and to smoke tobacco (OR 2.4, CI 0.9 to 6.6). Dose-response effects were seen for passive smoke exposure and risk of disease in all age groups. CONCLUSION: Tobacco smoke exposure independently increases the risk of developing meningococcal disease.

Characterisation of Haemophilus spp. isolated from infant conjunctivitis.

Haemophilus strains isolated from children under the age of 11 months with conjunctivitis were characterised by biotype, sugar fermentation, plasmid pattern and outer-membrane-protein profiles. H. influenzae was the most common species identified and was separated into 14 groups based on sugar fermentation and biotype patterns and into more than 20 groups when plasmid and outer-membrane-protein profiles were included. Small (mol. wt less than 10 X 10(6)) plasmids were identified in 11 of 34 (32%) H. influenzae isolates, 1 of 2 H. haemolyticus and 4 of 6 (67%) H. parainfluenzae isolates. Examination of sugar-fermentation and plasmid patterns increased the ability to distinguish between strains isolated at different times from recurrent disease and may have general applications in the study of Haemophilus strains isolated from a single anatomical site.

An interview study of participants in the Tacoma, Washington, syringe exchange.

Although European and Australian studies of syringe exchange programs have reported safer injection among participants and no increase in drug use, the generalizability of these findings to the US is uncertain. We report on the operations and potential effectiveness of the longest-operating syringe exchange in the US and compare our results to studies of exchange programs outside the US. The sample of 204 study subjects reported no change in the frequency of injection, from 155 to 152 injections per month, and a decline in the frequency of unsafe injections, from 56 to 30 times per month, while participating in the program. In all studies, participants report reduction in unsafe injections, and no increase in illicit drug use. However, the comparison also suggests that a high proportion of Tacoma exchangers have higher initial rates of drug injection, unsafe injection and homelessness, all of which were associated with unsafe injection while using the exchange. These indicate a need for additional services but that the Tacoma program is no less effective than European and Australian programs.

Chlamydia trachomatis infections in adolescents.

The guidelines of the Centers for Disease Control should be applied with appreciation of their limitations. The serious sequelae of chlamydial infections in young patients warrant vigorous antichlamydial therapy and specific microbiologic diagnosis. Until public health authorities implement control programs, the efforts of individual practitioners will probably be the mainstay of the flight against C. trachomatis.

Epidemiology of sexually transmitted diseases.

In the past decade, the recognized spectrum of sexually transmitted diseases has widened to a complex array of agents and syndromes. The authors correlate diseases with responsible pathogens and discuss the numerous and interrelated changes in industrialized societies that have contributed to the epidemics of sexually transmitted diseases.

PIP: The spectrum of sexually transmitted diseases has widened over the past decade and the treatment and control of these diseases have become a common concern in private and institutional practice. This article analyzes the factors influencing the spread of sexually transmitted diseases, details their complications, and provides guidelines for reporting and contact tracing. Although surveys of sexual behavior, fertility, and morbidity have failed to address the epidemiology of sexually transmitted diseases, numerous changes in industrialized societies are considered to have contributed to their dramatic spread, including changes in the age structure of the population, increasing numbers of homosexual men, declines in the age at 1st intercourse, greater numbers of single and divorced persons and a preference for hormonal contraceptives and IUDs. Adaptive changes in the pathogens that cause these diseases, e.g., resistance to antimicobials developed by N. gonorrhoeae, have further influenced the clinical epidemiology of these diseases. Complications of sexually transmitted diseases include pelvic inflammatory disease, ectopic pregnancy, infertility, and cervical cancer. Urologists should report cases of syphilis, penicillinase-producing N. gonorrhoeae, and gonococcal pelvic inflammatory disease. In cases of other diseases, reasonable measures should be taken to treat the patient's sexual partners and specific etiologic diagnosis should be made. If specific diagnosis is not possible, certain syndromes (e.g., urethritis and macropurulent cervicitis) should be managed as if they were sexually transmitted.

Cyclosporin A: tissue levels following topical and systemic administration to rabbits.

Plasma and aqueous levels of cyclosporin A (CsA) were determined following topical administration of CsA 1% to healthy rabbit eyes and compared with levels obtained when administered to rabbit eyes which had received corneal grafts 7-10 days previously. In addition plasma levels were determined following intramuscular administration of 50 mg CsA and the results compared with those obtained following topical administration. Topical administration to healthy rabbit eyes five times a day for three days resulted in plasma levels of CsA which were similar to those obtained over three days following an intramuscular administration of 50 mg CsA. The plasma levels in both were significantly higher than those obtained following topical administration to rabbit eyes which had received corneal grafts 7-10 days previously. Aqueous levels of CsA were lower than plasma levels, and there was no significant difference between levels obtained when CsA was administered topically to healthy eyes, to eyes which had received corneal grafts, or to the fellow eye.

A placebo-controlled blind trial of cyclosporin-A in prevention of corneal graft rejection in rabbits.

Cyclosporin-A (CyA) administered to rabbits intramuscularly in a dose of 25 mg/kg/day for 14 days following interlamellar corneal grafting had a significant effect in preventing rejection of the corneal graft (p less than 0.05), and the benefit was maintained. Rejection was attended by an initial mild inflammatory reaction and followed by a protracted intense response involving a variety of cell types, with subsequent loss of epithelium. endothelium and keratocytes, and the development of areas of stromal necrosis. CyA suppressed this rejection response.

Experimental infection of baboons (Papio cynocephalus anubis) with Chlamydia pneumoniae strain 'TWAR'.

Two infant baboons (Papio cynocephalus anubis) were inoculated with Chlamydia pneumoniae strain 'TWAR', one in the conjunctiva, nasopharynx and oropharynx, the other in the trachea. Both remained well during 8 weeks of observation. C. pneumoniae infection persisted for at least 8 weeks after inoculation. Chlamydia pneumoniae seems to be of low virulence in baboons and capable of causing chronic infection.

Risk of perinatal transmission of Chlamydia trachomatis by mode of delivery.

We compared the transmission rate of Chlamydia trachomatis infection from infected women to their infants after various modes of delivery. After vaginal birth, Chlamydia trachomatis was isolated from 58 of 125 infants with a cephalic presentation, and serological evidence of chlamydial infection was found in another eight. C. trachomatis was isolated from the only infant with a frank breech presentation. After Caesarean birth, C. trachomatis was isolated from two of 10 infants born after rupture of the membranes and from one of six without prior rupture of the membranes. No serological evidence of infection was found in any of the culture-negative infants born by Caesarean section. By survival analysis, rates of transmission were significantly lower after Caesarean section with rupture of the membranes before delivery than after vaginal delivery. Infants born to infected women are at risk of C. trachomatis infection regardless of route of delivery.

The biomechanical effects of deep tissue support as related to brow and facelift procedures.

The adverse effects of increased tension across a healing wound are well known. However, the effect of closing a wound in layers in order to decrease tension on the epidermis has been a source of controversy. It is hypothesized that deep tissue support decreases skin tension upon wound closure. In order to clarify this issue, a two-part study was designed to address the immediate effects of deep tissue support in vitro using fresh-frozen cadavers and in vivo on patients undergoing scheduled surgery. Closing skin tension was measured at standard reference points in coronal brow lift and rhytidectomy procedures performed with and without galeal closure and superficial musculoaponeurotic system (SMAS) procedures, respectively. Deep tissue support was found to significantly (p less than 0.05) decrease skin tension at the time of skin closure at standard reference points in coronal brow lift and rhytidectomy procedures performed on fresh-frozen cadavers. Similar significant (p less than 0.05) decreases in closing skin tension also were found in vivo in patients undergoing similar surgical procedures. Stress relaxation was not found to play a significant role in contributing to this immediate decrease in closing skin tension. It would appear, therefore, that deep tissue support, in the form of galeal closure and an SMAS procedure in coronal brow lift and rhytidectomy procedures, respectively, provides increased viscoelastic support, producing immediate significant decreases in closing skin tension in these procedures. The beneficial effects on wound healing, scar formation, tension-related trophic skin changes, and possible improved long-term results are discussed.