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J Paavonen

Publications and source records attributed to J Paavonen.

At least 19 recordsLinked to original sources

A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection.

BACKGROUND: Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors. METHODS: We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases. RESULTS: Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA: The risk was highest among those with HPV type 16 or 18 infection (adjusted relative risk as compared with that in women without HPV infection, 11; 95 percent confidence interval, 4.6 to 26; attributable risk, 52 percent). All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV. After adjustment for the presence of HPV infection, the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse, the presence of serum antibodies to Chlamydia trachomatis, the presence of serum antibodies to cytomegalovirus, and cervical infection with Neisseria gonorrhoeae. CONCLUSIONS: Cervical intraepithelial neoplasia is a common and apparently early manifestation of cervical infection by HPV, particularly types 16 and 18.

Adolescent

Pre- and posttreatment serum antibody responses to HPV 16 E2 and HSV 2 ICP8 proteins in women with cervical carcinoma.

Serum antibodies to early proteins of human papillomavirus type 16 (HPV 16 E2 protein) and herpes simplex virus type 2 (HSV 2 ICP8) can be measured by ELISA. In the serum of 122 newly diagnosed cervical carcinoma patients and age-matched controls, enhanced IgA antibody levels to an HPV-16 E2 protein derived peptide no. 245 indicated a 9.5-fold (95% confidence limits 2.8-57.2) relative risk of cervical carcinoma. No significant risk was found with a corresponding HPV 6 E2 peptide or HSV 2 ICP8. To evaluate the HPV 16 E2 peptide as a possible tumor marker for cervical carcinoma serial postoperative serum samples were tested from 27 women with cervical carcinoma. Antibody responses to the HPV 16 E2 peptide depended on the clinical stage. Stage I and II patients showed decreasing posttreatment IgA and/or IgG antipeptide antibody levels. Stage III and IV patients initially showed decreasing antipeptide antibody levels followed by increasing levels. These patients also showed increasing IgG antibody levels to the HSV 2 ICP8. However, increasing antibody levels to the HPV 16 E2 peptide indicated significantly (P less than 0.05) worse 2-year disease free survival (recurring disease) than did stable or decreasing antibody levels. The results suggest that serum antipeptide antibodies to the HPV 16 E2 peptide no. 245 can be used for the monitoring of cervical carcinoma.

Adenocarcinoma

Clinical presentation and outcome of listeriosis in patients with and without immunosuppressive therapy.

Seventy-four cases of systemic listeriosis occurring from 1971 to 1989 in the greater Helsinki area in Finland are reviewed with a special interest in the effect of preceding immunosuppressive therapy on the clinical presentation. Of these patients, 66% had an underlying disease, most commonly malignancy, diabetes mellitus, or renal transplantation, and 43% had received immunosuppressive therapy within 1 week before onset of listeriosis. Bacteremia and central nervous system infections (both in 43% of cases) were the most common clinical entities. The percentage of patients with meningitis was not greater among immunosuppressed patients (13/32, 41%) than among patients with underlying diseases not treated with immunosuppressive agents (9/16, 56%) or among previously healthy nonpregnant hosts (7/11, 64%). Immunosuppressed patients did not die more frequently than did those with underlying diseases not treated with immunosuppressive therapy (case fatality rate, 29% vs. 38%, respectively). However, all previously healthy non-neonatal patients survived, whereas 32% (15/47) of those with any kind of underlying disease succumbed.

Adolescent

A T-helper cell epitope overlaps a major B-cell epitope in human papillomavirus type 18 E2 protein.

Cultivated CD4+ T-helper cells from two patients with cervical adenocarcinoma showed responses to a peptide EKTGILTVTYHSETQRTK derived from an E2 protein of human papillomavirus type 18 (HPV 18), but not to a corresponding HPV 16 peptide (HKSAIVTLTYDSEWQRDQ). Serum antibodies in the HPV 18 peptide were also demonstrated in these patients. The GILT motif resembles a common pattern present in many T-cell epitopes, and is located at the beginning of an 11-amino acid-long A-helix structure close to the carboxyterminal end of HPV 18 E2. We conclude that two epitopes (a T-helper cell epitope and a B-cell epitope) overlap in the HPV 18 E2.

Amino Acid Sequence

Predominance of serum antibodies to synthetic peptide stemming from HPV 18 open reading frame E2 in cervical adenocarcinoma.

AIMS: To determine if there are type specific differences in serum antibody responses to synthetic peptides derived from human papillomavirus (HPV) open reading frame (ORF) E2 in patients with cervical carcinoma. METHODS: Diagnostic phase sera from 88 age-matched women with cervical adenocarcinoma (AC), cervical squamous cell carcinoma (SC), ovarian cancer (OC) or no gynaecological malignancy were available. Serum IgG and IgA antibodies to synthetic peptides corresponding to a residue of HPV 6, 11, 16, and 18 ORF E2 18 amino acids long and a control peptide from mumps virus were determined by ELISA. RESULTS: Both IgA and IgG antibody positivity to the HPV 18 peptide were associated with increased risk (9.0-fold, confidence limits 1.5-199) for AC. IgA positivity to HPV 11, 16, and 18 peptides was associated with an increased risk for SC. However, the association of IgG antibodies to HPV 16 peptide with SC was not significant. IgA or IgG antibodies to HPV 6 or mumps virus peptides were not associated with increased risk for AC, SC, or OC. CONCLUSIONS: These results suggest a specific role for HPV 18 in AC. Differences in antibody responses to HPV peptide in AC and SC suggest immunopathogenetic differences between the two types of cervical carcinoma.

Adenocarcinoma

Human papillomavirus infection of the female genital tract: correlation of HPV DNA with cytologic, colposcopic, and natural history findings.

Although molecular biology evidence suggests a strong link between HPVs and anogenital neoplasias, evidence from clinical studies is still less convincing. Thus, the recognition of both overt and subclinical HPV infection has become increasingly important. We studied the correlation between HPV DNA and cytologic, colposcopic and natural history findings in a defined group of women. The study population consisted of 150 HPV DNA positive cases (mean age 25.7 years, SD 7.4) and 69 randomly selected HPV DNA negative controls (mean age 27.3 years, SD 7.9) enrolled in an ongoing study of the natural history of genital HPV infections. All cases and controls had normal cervicovaginal cytology at the enrollment. A commercial dot-blot technique hybridization test (Virapap and Viratype, Digene Diagnostics, USA) was used for HPV DNA testing of cervicovaginal scrapes. Five percent of the patients had HPV 16/18, 31% had HPV 31/33/35, 15% had more than one of the three HPV DNA groups ("mixed"), and 15% had untypable HPV DNA. Cases and controls were followed by repeat examinations every 4th month. The mean follow-up time was 12.2 months (SD 8.7) for the cases, and 12.8 months (SD 6.9) for the controls. The study endpoint was defined as the presence of cytologic changes consistent with CIN. The overall prevalence of atypical transformation zone (ATZ) findings was 45% in the controls and 56% in the cases, with no significant differences between the specific HPV DNA groups. Although vulvar or vaginal abnormalities (acetowhite epithelium, squamous papillomatosis, filaments, satellite lesions, fissures, papules or exophytic condylomas) were more commonly seen in the cases than in the controls, the difference was significant only for condylomas and fissures.(ABSTRACT TRUNCATED AT 250 WORDS)

Colposcopy

Enhanced tenascin expression in cervical and vulvar koilocytotic lesions.

Tenascin is an extracellular matrix glycoprotein that is widely expressed during embryogenesis. In adults, it is restricted to select sites, including certain epithelial-stromal interfaces, but is notably enhanced in active inflammatory-reactive processes and in the stroma of many neoplasms. The authors immunostained with the monoclonal antibody (MAb) 100EB2 cryosections of vulvar and cervical biopsies displaying convincing koilocytosis with variable degrees of hyperplasia-dysplasia; in situ carcinomas were included. The presence of human papillomaviruses (HPV) 6, 11, 16, 18, 31, or 33 was confirmed by in situ hybridization in a subset of cases. Findings were compared with normal controls. The study was extended with the MAb 143DB7 that reacted with tenascin in paraffin sections. In normal samples, tenascin immunoreaction appeared as a delicate, continuous rim, in the immediate vicinity of the laminin staining; in parakeratotic areas, the rim was thicker. In foci of hyperplastic-dysplastic epithelium with or without koilocytosis, a distinct increase in tenascin staining was noted; enhanced tenascin often paralleled increasing hyperplasia and dysplasia. In most cervical and vulvar carcinomas in situ, the reactions were intense and extended deeply and raggedly into the underlying stroma. Tenascin was selectively enhanced in the endocervical stroma around inflammed or metaplastic glands. The authors conclude that tenascin is increased in HPV infection associated with epithelial proliferation. Enhancement was most consistently strong and extensive in in situ carcinomas, suggesting a correlation with active phases of epithelial growth and stromal remodeling.

Cell Adhesion

Transvaginal sonographic findings in ambulatory patients with suspected pelvic inflammatory disease.

OBJECTIVE: To evaluate transvaginal sonographic findings in ambulatory patients with suspected pelvic inflammatory disease (PID). METHODS: We studied 51 outpatients with a mean age of 26.8 years (range 16-52) who had a history of low abdominal pain, negative pregnancy test, and no gynecologic procedures performed during the last month. Endometrial biopsy was used for the histopathologic diagnosis. The presence of plasma cell endometritis was used as the criterion standard for the diagnosis of PID. Sonography was performed before biopsy in a blinded fashion without knowledge of the clinical findings and laboratory results except for the pregnancy test. Repeat pelvic and ultrasound examinations were performed 4 weeks after antimicrobial therapy. RESULTS: Endometrial biopsy revealed plasma cell endometritis in 13 cases (25%). Thickened fluid-filled tubes were seen in 11 of 13 patients (85%) with plasma cell endometritis and in none of those without. Other sonographic findings associated with plasma cell endometritis were polycystic-like ovaries and free pelvic fluid. A sonogram suggestive of PID, ie, thickened fluid-filled tube with or without free pelvic fluid, had a sensitivity of 85% and a specificity of 100% for the diagnosis of plasma cell endometritis. None of the patients with a normal sonogram or simple cyst had plasma cell endometritis. Repeat examination after 4 weeks showed that the sonographic findings had resolved in 60% of the patients who had had histologic evidence of infection. CONCLUSION: Transvaginal sonography can facilitate the outpatient management of patients with suspected PID.

Adolescent

Chlamydia trachomatis in acute salpingitis.

In a study to evaluate the possible role of Chlamydia trachomatis and Neisseria gonorrhoeae in acute salpingitis, 26% of 106 patients with severe symptoms had positive culture results for C. trachomatis; 43% of the 72 patients from whom paired sera were obtained had either positive culture results for or seroconversion in the single antigen immunofluorescence test to C. trachomatis. Twenty-six per cent of patients harboured N. gohorrhoeae and 14% had gonococcal complement-fixing antibody titres greater than or equal to 8. Intrauterine devices were used by 48% of patients, no difference being found in the frequency of use between patients harbouring C. trachomatis or N. gonorrhoeae. The possible role of C. trachomatis should be considered in the treatment of acute salpingitis.

Acute Disease

Genital Chlamydia trachomatis infections in patients with cervical atypia.

Of 177 gynecologic outpatients with cervical dysplasia studied, 29 (16%) were found to excrete Chlamydia trachomatis from their urogenital tract. Sera collected from 93 of these patients were significantly more often positive for and showed higher levels of antichlamydial micro-complement fixation (CF) and immunofluorescence (IF) antibodies than sera obtained from the controls. However, when the sera were tested for anti-herpesvirus type II (HSV-II) and cytomegalovirus (CMV) antibodies, no difference between the cases and the controls were encountered.

Adolescent

Chlamydial infections. Microbiological, clinical and diagnostic aspects.

The agent of trachoma, originally regarded as a virus, was described by Halberstadter and von Prowacek in 1907. Since then, studies on Chlamydiae have shown that they are procaryocytic organisms that infect eucaryocytic cells as obligate intracellular parasites. Infections caused by these pathogenic agents occur in a wide range of avian and mammalian species. Chlamydiae are also responsible for several diseases in man, and there is a rapidly growing awareness of their public health significance. The aims of this review are to describe the microbiology and laboratory diagnosis of Chlamydiae and to reflect the clinical spectrum of human chlamydial diseases.

Animals

Erythromycin and lymecycline treatment in chlamydia-positive and Chlamydia-negative non-gonococcal urethritis--a partner-controlled study.

A group of 213 men with non-gonococcal urethritis and their sexual partners were treated either with erythromycin stearate 500 mgx2 for 15 days or with lymecycline 300 mgx2 for 10 or 20 days. Chlamydia trachomatis was isolated from 40% of the men, from 26% of their female partners and from 56% of the partners of men with chlamydia-positive urethritis. One hundred and eighty-one men were available for evaluation of therapy. There were no significant differences between the treatment schedules. The cure rate was 86-90% in men with chlamydia-positive and 89-100% in men with chlamydia-negative urethritis. Four of the 17 chlamydia-positive females treated with erythromycin and 2 of the 20 chlamydia-positive females treated with lymecycline for 10 days still had chlamydia at re-examination.

Chlamydia Infections

Single-antigen immunofluorescence test for chlamydial antibodies.

A simple method is presented for producing large numbers of inclusions of Chlamydia trachomatis serotype L2 in cell cultures on slides for immunofluorescence antibody staining. Preliminary results with a total of 1,241 human sera from different groups were consistent with findings by earlier methods: 82% of chlamydia-positive men with nongonococcal urethritis had antibodies at titers of greater than or equal to 8, with a geometric mean titer (GMT) of 44.9; 68.5% of chlamydia-negative men with nongonococcal urethritis had titers of greater than or equal to 8, with a GMT of 38.6; 27% of male blood donors had titers of greater than or equal to 8, with a GMT of 19.6; 95.0% of chlamydia-positive women had titers of greater than or equal to 8, with a GMT of 80.3; 67.0% of chlamydia-negative partners of men with nongonococcal urethritis had titers of greater than or equal to 8, with a GMT of 47.0; 50.2% of control women had titers of greater than or equal to 8, with a GMT of 27.7% and 8.1% of children (aged 1 to 15 years) had titers of greater than or equal to 8, with a GMT of 17.8.

Adolescent

Genital chlamydial infections in patients attending a gynaecological outpatient clinic.

Investigation for genital chlamydial infections was carried out on 160 patients of fertile age attending a gynaecological outpatient clinic. Thirteen (9%) of the 144 patients with valid specimens were found to be Chlamydia-positive. Seven (54%) of them had antichlamydial antibodies by the complement-fixation test, and 11 (85%) antichlamydial antibodies by a single-antigen immunofluorescence test compared with 21 (16%) and 70 (53%), respectively, of the 131 Chlamydia-negative patients. Patients with overt genital chlamydial infection often complained of ocular and urethral symptoms. Usually there was clinical evidence of cervical infection as well as of inflammation on cervicovaginal smears. Colposcopical and histological examinations did not show any specific alterations.

Antibodies, Bacterial

Herpes simplex virus induces unscheduled DNA synthesis in virus-infected cervical cancer cell lines.

We evaluated herpes-simplex-virus-type-2(HSV2)-induced unscheduled DNA synthesis in virus-infected cervical cancer (HeLa, CaSki, C-33A, and SiHa) cells. HSV2 replication was approximately 100-fold more efficient in the HeLa cells than in less susceptible C-33A and SiHa cells. In dual parameter flow cytometric analysis of bromodeoxyuridine (BrdU) incorporation, HSV2-infected HeLa cells showed a rapid increase in the proportions of DNA-synthesizing G1- and S-phase cells, whereas in C-33A and SiHa cells, the proportions of DNA-synthesizing G1- and early S-phase cells were increased late in the infection. Blocking of HSV2 replication by phosphonoformate inhibited virus-induced changes in HeLa cells, but not in C-33A and SiHa cells. Anti-BrdU antibodies exhibited a coarse globular nuclear staining pattern in the C-33A cells, while the other cells showed speckled and/or fine globular nuclear fluorescence. Anti-ICP8 (HSV-specified major DNA-binding protein) antibodies revealed that, in C-33A cells, ICP8 remained in the cytoplasm, whereas in the other cells, speckled or globular nuclear fluorescence was found. Our results showed that HSV2 induced the unscheduled synthesis of cellular DNA, which was host-cell-dependent, and in virus infected C-33A cells, it may be attributable to both viral and cellular proteins.

Antibodies, Viral

Examination of men with nongonococcal urethritis and their sexual partners for Chlamydia trachomatis and Ureaplasma urealyticum.

Chlamydia trachomatis was recovered from 39 (52%) of 75 men who had nongonococcal urethritis and from 28 (37%) of their sexual partners. Of the partners of men with Chlamydia-positive nongonococcal urethritis, 64% excreted Chlamydia, compared with 8% of the partners of men with Chlamydia-negative nongonococcal urethritis. In contrast, an apparently sexual mode of transmission was not observed with Ureaplasma urealyticum. Rates of recovery of U. urealyticum from men with nongonococcal urethritis whose cultures were Chlamydia-positive and those whose cultures were Chlamydia-negative were the same. Significant seroconversion was detected bythe single-antigen immunofluorescence test in about 50% of patients who had Chlamydia-postive cultures.

Adult

Chlamydia trachomatis-induced urethritis in female partners of men with nongonococcal urethritis.

The rate of isolation of Chlamydia trachomatis from cervical and urethral specimens from 99 culture-positive female partners of men with nongonococcal urethritis who were attending a gynecological outpatient clinic was correlated with the clinical status of the women. The agent was recovered from both sites in 46 women, from the cervix only in 28, and from the urethra only in 25 women. Urethral symptoms were reported by 38 (54%) of those with positive urethral cultures, as compared with six (21%) of those with positive cervical cultures only (P less than 0.01). Significant bacteriuria was found in only three patients with urethral symptoms; two of them had negative urethral cultures for C. trachomatis. Frequencies of cervicitis, rises in titer of antibody, and geometric mean titers of immunofluorescent antibody to C. trachomatis did not differ significantly among the three groups.

Adolescent