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Biomedical subjects

R C Brunham

Publications and source records attributed to R C Brunham.

At least 91 records · Page 5Linked to original sources
PubMed1990

Effect of the menstrual cycle on detection and typing of human papillomavirus in uterine cervical cells.

We observe fluctuations in human papillomavirus detection and variation in genotyping between sequential cervical cell specimens analyzed by filter in situ hybridization. Furthermore, specimen adequacy for analysis varies. To determine whether these phenomena are correlated with menstrual cycle stage at the time of sampling, we analyzed cervical cell specimens from women with cervical intraepithelial neoplasia. Specimens were categorized on the basis of a 28-day menstrual cycle and were analyzed by hybridization to combined probes for virus types 6 and 11 or types 16 and 18. Specimen adequacy was determined by hybridization to a human Alu I repetitive deoxyribonucleic acid probe. Analysis of data with chi 2 revealed that fluctuations in virus detection and type variation are unrelated to menstrual cycle stage. Specimen adequacy is stage-dependent for women who take oral contraceptives. Whereas specimens can be collected at any time other than the first week of the menstrual cycle, accurate determination of infection status requires multiple assessments.

Cervix Uteri↗
PubMed1990

The dynamics of HIV spread: a computer simulation model.

Mathematical modeling of the AIDS pandemic has been limited by the difficulty of satisfactorily representing the marked behavioral heterogeneity that characterizes the various populations at risk. We propose an approach which models the spread of infection as a discrete-event simulation using SIMSCRIPT, a powerful simulation language. The program developed provides sufficient flexibility to adequately represent and study a wide range of risk-group dynamics. Using this tool we have verified the May-Anderson prediction relating contact rate heterogeneity to the rate of HIV spread. We have also been able to assess the sensitivity of the model to the particular choice of distribution for contact rates, disease stage durations, and intercontact intervals. It is thought that this approach will permit the empirical testing of hypotheses which do not lend themselves to a purely mathematical treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1990

A general model of sexually transmitted disease epidemiology and its implications for control.

Achieving control of STDs may be possible by integrating the activities discussed previously with further research to provide additional empiric data on sex behavior, to develop innovative strategies to access and communicate with those most at risk of STD (i.e., core-group members), and to foster biologic study of STD pathogens with the goal of vaccine development. New strategies to identify core-group members aside from the currently used STD-repeater status would be of immense help in targeting educational efforts, laboratory screening, and vaccines. Achieving more complete control of STDs may be possible if recent advances in our understanding of their epidemiology and transmission dynamics can be translated into effective new interventional strategies.

Disease Reservoirs↗
PubMed1990

Maternal gonococcal infection as a preventable risk factor for low birth weight.

With the objective of determining if specific sexually transmitted diseases (STDs) are associated with prematurity (birth weight less than or equal to 2500 g and gestational age less than or equal to 36 weeks), a case-control study was conducted to evaluate women for serologic evidence of syphilis and human immunodeficiency virus infection and microbiologic evidence of cervical infection with Neisseria gonorrhoeae, Chlamydia trachomatis, and Haemophilus species and vaginal infection with genital mycoplasma, Streptococcus agalactiae, and Enterobacteriaceae. Gram stains of vaginal secretions were evaluated for bacterial vaginosis. Among 166 cases and 175 controls, infection with N. gonorrhoeae was associated with preterm birth. Four percent of controls and 11% of cases were infected with N. gonorrhoeae (odds ratio 2.9, 95% confidence interval 1.2-7.2). This association was independent of age, rupture of membranes, and hypertension. Other STDs were not associated with preterm birth. The attributable risk of gonococcal infection was 14%. Gonococcal infection appears to be responsible for a substantial proportion of premature births and is theoretically preventable by antenatal case detection and treatment.

Adult↗
PubMed1990

The prevalence of Chlamydia trachomatis infection among mothers of children with trachoma.

The authors studied the epidemiology of Chlamydia trachomatis infection in a trachoma-endemic area of central Kenya. Children with abnormal ocular discharge were evaluated for clinical evidence of trachoma and were cultured for C. trachomatis. Isolated strains of C. trachomatis were immunotyped with monoclonal antibodies. Overall, 221 children from 207 families were evaluated. Clinically, 91 children (41%) had trachomatous follicular inflammation, and 130 (59%) had papillary hypertrophy without visible follicle and were labeled as having mucopurulent conjunctivitis. C. trachomatis was isolated from 31 of 91 children with trachoma (34%) and 17 of 130 children with conjunctivitis (13%) (p less than 0.001). Twenty-two C. trachomatis strains were immunotyped: 17 were from children with trachoma (nine type A, one A/L2, five B, one Ba, and one E) and five were from children with conjunctivitis (two A, one Ba, one D, and one F). A total of 168 mothers were evaluated for cervical C. trachomatis infection, and seven (4%) were culture-positive. Two strains were immunotyped as serovar E. The authors conclude that C. trachomatis ocular infections are due to heterogeneous serovars in this area, that most cases of trachoma are due to C. trachomatis infection with the classic trachoma serovars (A, B, or Ba), and that cervical C. trachomatis infection is uncommon among mothers of children with trachoma.

Adolescent↗
PubMed1990

Infection with HIV as a risk factor for adverse obstetrical outcome.

We carried out a case-control study to investigate the role of sexually transmitted diseases (STDs), including infection with HIV, as risk factors for adverse outcome of pregnancy. Overall, 1507 women were enrolled within 24 h of delivery. Cases (n = 796) were mothers of low-birthweight infants (less than 2500 g) or of stillborns. Low-birthweight infants were divided into preterms (n = 373) and neonates small for gestational age (n = 234). Stillborns were separated into intrauterine fetal deaths (n = 120), and intrapartum fetal deaths (n = 69). Controls were selected from mothers delivering a live baby of greater than or equal to 2500 g (n = 711). The maternal HIV seroprevalence in the control group was 3.1%. Prematurity was associated with maternal HIV antibody [8.6% seropositive; adjusted odds ratio (OR) 2.1; 95% confidence interval (CI) 1.1-4.0], as was being born small for gestational age (7.7% seropositive; adjusted OR 2.3; 95% CI 1.2-4.2). In mothers who delivered a stillborn baby, both intrauterine fetal death (11.7% seropositive; adjusted OR 2.7; 95% CI 1.3-5.5) and intrapartum fetal death (11.6% seropositive; adjusted OR 2.9; 95% CI 1.3-6.5) were independently associated with HIV seropositivity in the mother. Maternal syphilis was confirmed as an important risk factor for intrauterine fetal death (14.3% positive; adjusted OR 4.8; 95% CI 2.4-9.5). No significant association was found between other STDs, including gonococcal and chlamydial infection, and adverse obstetrical outcome. These results suggest an association between maternal HIV infection and adverse obstetrical outcome, defined as low birthweight and stillbirth.

Abortion, Spontaneous↗
PubMed1990

Randomized, double-blind comparison of the efficacies, costs, and vaginal flora alterations with single-dose ceftriaxone and multidose cefazolin prophylaxis in vaginal hysterectomy.

A comparison of efficacies, costs, and effects on vaginal microflora of one preoperative and three postoperative 1-g doses of cefazolin versus those of one preoperative 1-g dose of ceftriaxone was done with 65 and 73 women, respectively, undergoing elective vaginal hysterectomy. Patient infection rates were not statistically different between the cefazolin group (six events in 6 of 73 patients [8.2%]) and the ceftriaxone group (11 events in 9 of 65 patients [13.8%]). Side effects, including diarrhea, were minimal and similar between the two groups. Significant shifts in the cervicovaginal microflora of the patients occurred postoperatively, with a marked increase in enterococci and a drop in nonenterococcal streptococci. No shifts among aerobic, facultative gram-negative rods and staphylococci were observed. Among the anaerobes, a significant decrease in the number of patients harboring nonsporulating, gram-positive rods and a less striking concomitant increase in Bacteriodes species and members of the family Peptococcaceae were noted. No qualitative differences were noted between the two groups that received prophylactic therapy. Aside from enterococci, cefazolin or ceftriaxone resistance among vaginal isolates (greater than or equal to 10(3)/ml) was minimal. Selection of resistant isolates was not different between the treatment groups. We could not detect a difference between a single 1-g dose of ceftriaxone and multidose cefazolin for infection prophylaxis in patients undergoing a vaginal hysterectomy. However, the total acquisition, preparation, and administration costs were greater for the ceftriaxone regimen than they were for the cefazolin regimen. Cefazolin should therefore remain the drug of choice for infection prophylaxis in uncomplicated vaginal hysterectomies.

Bacteria↗
PubMed1990

The 75-kilodalton protein of Chlamydia trachomatis: a member of the heat shock protein 70 family?

The gene encoding a 75-kilodalton (kDa) protein of Chlamydia trachomatis was cloned, expressed, and sequenced. Genomic libraries from C. trachomatis serovar D DNA were constructed in vectors pUC18 and lambda gt11 and were screened with a panel of monoclonal antibodies against C. trachomatis antigens. The only recombinants identified were those that reacted with antibody UM-13, which has specificity for a genus-specific epitope on the 75-kDa protein. The gene was localized to a 2.9-kilobase DNA fragment and sequenced. The gene consists of a long open reading frame of 1,956 nucleotides, which translates into 652 amino acids totalling 70,558 daltons in mass. Putative promoter elements and a ribosome binding site were identified within 5'-flanking sequences, and a typical rho-independent terminator was identified within 3'-flanking sequences. Screening of the GenBank nucleic acid sequence data bank revealed extensive similarity between the chlamydial 75-kDa gene and the heat shock protein 70 (hsp70) family or proteins. In particular, 71 and 69% amino acid sequence similarities were identified with hsp70 of Escherichia coli and Bacillus megaterium, respectively. Polyclonal antibodies were produced to the recombinant antigen in rabbits and detected epitopes on elementary bodies in enzyme-linked immunosorbent and indirect microimmunofluorescence assays. Antibodies reacted with an antigen of identical molecular mass in L2 and C serovars in an immunoblot assay and neutralized these serovars in cell culture. The 75-kDa protein appears to be a chlamydial homolog of hsp70, is immunoaccessible on native elementary bodies, and is a target for neutralization.

Amino Acid Sequence↗
PubMed1990

Immunoaccessible peptide sequences of the major outer membrane protein from Chlamydia trachomatis serovar C.

The antigenicity of the major outer membrane protein of Chlamydia trachomatis serovar C was assessed by using overlapping hexapeptide homologs of serovar C major outer membrane protein and rabbit antisera in a peptide enzyme-linked immunosorbent assay. Five immunogenic sites were found distributed within variable sequences of the protein: four were immunodominant and three were surface exposed on native elementary bodies of serovar C. None was surface exposed on serovars H, I, and J.

Amino Acid Sequence↗
PubMed1990

Immunologic characterization of a cloned fragment containing the species-specific epitope from the major outer membrane protein of Chlamydia trachomatis.

A 183-bp fragment encoding variable domain IV (VD IV) of Chlamydia trachomatis serovar B major outer membrane protein (MOMP) (amino acids 273 to 333) and containing the species-specific epitope was cloned and expressed in Escherichia coli as a fusion protein with Schistosoma japonicum glutathione S-transferase (GST-VD IV). The fusion protein was affinity purified under nondenaturing conditions and used to immunize rabbits. Antisera were characterized by microimmunofluorescence, immunoblot, dot blot, peptide enzyme-linked immunosorbent, and in vitro neutralization assays. Antisera recognized MOMP from all 12 tested serovars of C. trachomatis but not from Chlamydia psittaci. In a dot blot assay, antisera bound to elementary bodies of serovars B, D, E, L2, and K in a strong fashion and to elementary bodies of serovars F, G, A, and H in a weak fashion but not to elementary bodies of serovars C, J, and I. High-resolution peptide mapping with synthetic overlapping serovar B MOMP peptides in a solid-phase enzyme-linked immunosorbent assay showed that immunization with GST-VD IV produced a serologic response that closely mimicked the response produced with purified serovar B elementary bodies. Antipeptide antibodies with strong binding to species- and subspecies-specific epitopes were elicited. Antisera were able to neutralize only those C. trachomatis serovars that bound antibodies in the dot blot assay. These results suggest that antigenic fragments from VD IV containing the species-specific epitope may be useful in the construction of a chlamydial vaccine for some but not all C. trachomatis serovars.

Animals↗
PubMed1990

Mapping antigenic sites on the major outer membrane protein of Chlamydia trachomatis with synthetic peptides.

The antigenicity of the major outer membrane protein (MOMP) of Chlamydia trachomatis was comprehensively evaluated by using overlapping hexapeptide homologs of serovar B MOMP and polyclonal rabbit antisera in a peptide enzyme-linked immunosorbent assay. Of 367 hexapeptides, 152 showed reactivities with at least one antiserum. Seven hexapeptides located within variable domain (VD) IV (residues 288 to 316) were found to be most reactive in terms of their binding titer and frequency, suggesting that VD IV is the immunodominant region within the MOMP as detected by this assay. Peptide-reactive antibodies could also recognize corresponding epitopes on either viable or acetone-permeabilized organisms. The antigenic specificity and immunoaccessibility of epitopes located in VD IV were resolved by absorbing antisera with chlamydial elementary bodies. Six antigenic sites were found in this region and included a B-type-specific site (S1), four subserogroup-specific sites (S2 and S4 to 6), and one species-specific site (S3), each displaying varying degrees of surface exposures on elementary bodies from different C. trachomatis serovars.

Animals↗
PubMed1990

Chlamydial heat shock proteins and trachoma.

Two chlamydial proteins (HSP-60 and HSP-70) have marked homology with bacterial and mammalian heat shock proteins. Previous studies have indicated that when inoculated into the eyes of immune animals, a Triton X-100 extract of chlamydia containing HSP-60 induces an ocular delayed-type hypersensitivity reaction. The potential for HSP-70 to induce a similar reaction was tested in six cynomolgus monkeys that had been sensitized to both antigens by previous ocular chlamydial infection. Whereas the chlamydial extract containing HSP-60 induced a marked clinical response within 24 h of inoculation, no response followed inoculation of HSP-70 in the contralateral eye. The lack of a response to HSP-70 suggests that further assessment of its potential as a trachoma vaccine is warranted.

Animals↗
PubMed1989

Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men.

To determine the frequency and risk factors for female to male sexual transmission of human immunodeficiency virus type 1 (HIV-1), a prospective study was carried out in 422 men who had acquired a sexually transmitted disease (STD) from a group of prostitutes with a prevalence of HIV-1 infection of 85%. The initial seroprevalence of HIV among the men was 12%. 24 of 293 (8.2%) initially seronegative men seroconverted to HIV-1. Newly acquired infection was independently associated with frequent prostitute contact (risk ratio 3.2, 95% confidence interval 1.2-8.1), with the acquisition of genital ulcer disease (risk ratio 4.7, 95% confidence interval 1.3-17.0), and with being uncircumcised (risk ratio 8.2, 95% confidence interval 3.0-23.0). 96% of documented seroconversions occurred in men with one or both of the latter two risk factors. In a subgroup of 73 seronegative men who reported a single prostitute sexual contact, the frequency of HIV-1 infection was 8.2% during 12 weeks of observation. No man without a genital ulcer seroconverted. A cumulative 43% of uncircumcised men who acquired an ulcer seroconverted to HIV-1 after a single sexual exposure. These data indicate an extremely high rate of female to male transmission of HIV-1 in the presence of STD and confirm a causal relation between lack of male circumcision, genital ulcer disease, and susceptibility to HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Epidemic of nosocomial Legionnaires' disease in renal transplant recipients: a case-control and environmental study.

An outbreak of Legionella pneumophila pneumonia occurred in 6 of 49 new renal transplant recipients over the course of 13 months. We compared infected patients (cases) and uninfected patients (controls) with respect to potential risk factors. Corticosteroid use, need for hemodialysis and number of days of hemodialysis were significantly greater among the cases. Logistic regression analysis identified corticosteroid dosage and number of days of hemodialysis as independent risk factors. Lymphopenia and monocytopenia were correlated with the amount of corticosteroid administered and occurred to a greater degree in the cases. All clinical isolates were of L. pneumophila serogroup 1, subtype Philadelphia 1, which was also cultured from a recovery room sink outside the operating room where the transplants were done. Other areas of the hospital were colonized with other, heterogeneous strains of L. pneumophila. The organism was not eliminated from the hospital water supply despite shock chlorination and superheating of water tanks. The epidemic ended when new transplant recipients routinely received prophylactic trimethoprim-sulfamethoxazole (160-800 mg given orally once daily) while in hospital after transplantation. Corticosteroid-induced monocytopenia and lymphopenia and the complement activation and monocyte depletion effects of hemodialysis may combine to increase susceptibility to Legionnaires' disease.

Adult↗
PubMed1989

Comparison of filter in situ deoxyribonucleic acid hybridization with cytologic, colposcopic, and histopathologic examination for detection of human papillomavirus infection in women with cervical intraepithelial neoplasia.

Material from uterine cervical scrapings of 98 women with cervical intraepithelial neoplasia were analyzed by filter in situ hybridization for human papillomavirus infection. Concurrently obtained Papanicolaou smears and colposcopically directed biopsy specimens were also examined for papillomavirus infection. Hybridization was superior to cytologic and colposcopic examinations and was equivalent to histopathologic study for papillomavirus detection. Infection with virus types 6 and/or 11 was associated with milder disease, whereas virus types 16 and/or 18 infection alone or in association with types 6 and/or 11 was associated with more severe disease. Because papillomavirus infection may not be detected by cytologic or colposcopic examination and specific virus types have been documented to be associated with invasive disease, deoxyribonucleic acid hybridization analysis for at least these virus types should be carried out in conjunction with conventional procedures when evaluating women with cervical disease. Filter in situ hybridization is a simple, rapid, noninvasive procedure and has enhanced diagnostic value over conventional procedures by defining infecting virus types.

Cervix Uteri↗
PubMed1989

Randomized treatment of mucopurulent cervicitis with doxycycline or amoxicillin.

A randomized trial of doxycycline versus amoxicillin was performed to treat mucopurulent cervicitis. Chlamydia trachomatis, the most common single agent associated with mucopurulent cervicitis, was isolated from 30 (47%) and Neisseria gonorrhoeae from five (8%) of 64 patients. Patients were followed up for 3 months, and the effect of treatment was assessed by clinical (presence of endocervical mucopus, cervicitis severity score, and number of polymorphonuclear leukocytes on Gram-stained smears of endocervical secretions) and microbiologic criteria. Doxycycline and amoxicillin were equally effective for treating chlamydial and nonchlamydial cervicitis. However, endocervical mucopus was still present in 18% of the patients in both treatment groups after 2 months and in 23% of the doxycycline group and 33% of the amoxicillin group after 3 months of therapy. The cause of persistent/recurrent mucopus after antimicrobial treatment was not explained by relapse or reinfection with Chlamydia trachomatis, Neisseria gonorrhoeae, genital mycoplasmas, or Gardnerella vaginalis, but persistence was associated with the degree of cervical ectopy.

Amoxicillin↗
PubMed1989

High-resolution 31P nuclear magnetic resonance study of Chlamydia trachomatis: induction of ATPase activity in elementary bodies.

ATPase activity of elementary bodies (EBs) of Chlamydia trachomatis was investigated by using high-resolution 31P nuclear magnetic resonance spectroscopy. ATPase activity was detected in EBs of C. trachomatis serovars A, B, and L2 after treatment with the reducing agents 2-mercaptoethanol and glutathione. ATPase activity was oligomycin sensitive and magnesium ion dependent. EBs heated at 60 degrees C for 10 min or pretreated with Triton X-100 before exposure to 2-mercaptoethanol did not exhibit ATPase activity. Monoclonal antibody to the major outer membrane protein abrogated ATPase activity of EBs, whereas monoclonal antibody to chlamydial lipopolysaccharide only marginally reduced the level of ATPase activity. These findings suggest that EBs possess intrinsic ATPase activity and that cysteine-rich outer membrane proteins of EBs are important in the regulation of ATPase activity. The major outer membrane protein may be the major route through which ATP accesses ATPase.

Adenosine Triphosphatases↗