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Biomedical subjects

J Paavonen

Publications and source records attributed to J Paavonen.

At least 127 records · Page 7Linked to original sources

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↗

Natural history of vaginal intraepithelial neoplasia.

The natural history of vaginal intraepithelial neoplasia (VAIN) was studied in 23 patients followed for at least 3 years with no treatment. The mean age of the patients was 41 years of age. A large proportion of the VAIN lesions (50%) were multifocal, and approximately one half of the lesions were associated with concomitant cervical or vulvar intraepithelial neoplasia. Progression to invasive vaginal carcinoma occurred in two (9%) cases, persistence of VAIN occurred in three (13%) cases, and regression of VAIN occurred in 18 (78%) cases. The risk for progression to invasive carcinoma emphasizes the significance of colposcopic examination of the vagina with directed biopsy specimens obtained from all lesions.

Adult↗

Combination antimicrobial therapy in the treatment of acute pelvic inflammatory disease.

We compared the clinical and microbiologic efficacy of two broad-spectrum combination antimicrobial regimens in the treatment of 148 patients with acute pelvic inflammatory disease. Patients were randomized to inpatient treatment with either cefoxitin and doxycycline (n = 75) or clindamycin and tobramycin (n = 73). These antibiotics were administered intravenously for at least 4 days, and up to 48 hours beyond defervescence. Patients were discharged on a regimen of oral doxycycline or clindamycin in accordance with the intravenous regimen to complete a total duration of therapy of 2 weeks. Neisseria gonorrhoeae (53%) and Chlamydia trachomatis (31%) were the microorganisms that were isolated most frequently from the genital tract of enrolled patients. At follow-up, N. gonorrhoeae was isolated in two patients, and C. trachomatis was isolated in none. The overall initial favorable response rate to combination antimicrobial therapy was 98.5% (130/132) in patients with uncomplicated pelvic inflammatory disease and 81% (13/16) in patients with pelvic inflammatory disease that was complicated by tuboovarian abscess. A greater than 70% decrease in abdominal tenderness score occurred in 89% of 111 patients within 6 weeks of hospital discharge. There were no significant differences between antibiotic treatment groups in any response categories or in toxicity. During the initial hospitalization, five patients (three with tuboovarian abscess; one with a pyosalpinx, and one with intractable acute and chronic pelvic inflammatory disease) required surgical intervention. These results support the recommendation to use broad-spectrum combination antimicrobial therapy for the treatment of acute pelvic inflammatory disease.

Acute Disease↗

Cervical human papillomavirus deoxyribonucleic acid and cytologic evaluations in gynecologic outpatients.

We studied the prevalence and cytologic manifestations of human papillomavirus deoxyribonucleic acid among 2668 gynecologic outpatients. The study population consisted of 1573 women who came into the emergency room, 623 women from an abortion clinic who were seen because of induced first-trimester abortion, and 472 women who had been referred to a colposcopy clinic because of an abnormal Papanicolaou smear finding. A dot blot technique was used for the detection of human papillomavirus types 6/11, 16/18, and 31/33/35. The prevalence of human papillomavirus deoxyribonucleic acid was 4.4% in the emergency room population, 8.8% in the abortion clinic population, and 31.4% in the colposcopy clinic population. Human papillomavirus type 16/18 was most prevalent (3.5%), followed by human papillomavirus type 31/33/35 (3.1%), and human papillomavirus type 6/11 was least prevalent (2.1%). Of all unselected human papillomavirus deoxyribonucleic acid-positive women who were enrolled from the emergency room or from the abortion clinic, 73% had normal cytologic evaluations. Twenty-five percent had benign atypia, and 2% had dyskaryotic changes. No human papillomavirus deoxyribonucleic acid type-specific differences were detected in the distribution of cytologic atypias.

Adolescent↗

Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix.

Many reports have shown a link between human papillomavirus (HPV) and cervical squamous neoplasia. However, the association of HPV with cervical adenocarcinoma has been studied less extensively. The authors evaluated the presence of HPV-DNA in 106 patients with adenocarcinoma of the uterine cervix by in situ hybridization, using 35S-labeled probes for HPV 16 DNA and HPV 18 DNA. The overall prevalence of HPV-DNA was 18% (19 of 106). HPV 16 was present in 2 (2%) cases, HPV 18 was observed in 15 (14%) cases, and both HPV 16 and HPV 18 were found in 2 (2%) cases. There was a correlation between HPV-DNA positivity and tumor stage (P less than 0.01) and tumor size (P less than 0.05), but there was no relationship between HPV-DNA positivity and tumor differentiation, proliferation (S-phase fraction), ploidy, lymph node metastases, or five-year survival rate. These results suggest that HPV 18 DNA is associated with cervical adenocarcinoma but the presence of HPV 18 has no influence on overall survival.

Adenocarcinoma↗

Subclinical manifestations of vulvar human papillomavirus infection.

We studied the presence of human papillomavirus (HPV) DNA by in situ hybridization in 74 colposcopically defined subclinical vulvar lesions obtained from 51 patients (mean age 25 years, range 18-42 years) referred for atypical Papanicolaou smears to the Colposcopy Clinic. Serial sections of formalin-fixed, paraffin-embedded biopsy tissue were stained by routine hematoxylin and eosin stain or were separately hybridized with biotin-labeled probes of HPV types 6, 11, 16, and 18 at high stringency and with mixed HPV probes at low stringency. Histologic evidence of HPV infection (koilocytosis or dysplasia) was found in eight lesions. Overall, 10 lesions were positive by in situ hybridization with HPV DNA. Although certain colposcopic features were more strongly associated with HPV DNA than others were, we were unable to demonstrate any consistent correlation between HPV DNA positivity or specific HPV DNA types and colposcopic categories. There was little correlation between HPV DNA positivity and the histopathologic incidence of HPV infection and dysplasia. Three of the 10 hybridization-positive lesions were severely dysplastic as compared with 0 of 64 nonhybridizing lesions. In spite of this association between HPV DNA and dysplasia, HPV DNA hybridization added no additional clinically relevant information to the histopathologic findings. We emphasize the significance of careful colposcopic examination of the vulva with directed biopsies.

Adult↗

General sexually transmitted diseases.

This review discusses current trends in sexually transmitted diseases. Topics include treatment and prevention of syphilis and gonorrhea, as well as the association of sexually transmitted diseases with sexual assault. Also discussed are the various organisms that cause vulvitis, including Trichomonas, Candida, and Gardnerella species, along with a discussion of vulvar lesions that are especially difficult to diagnose and treat. Diagnosis, sampling, pathogenesis, and treatment of Chlamydia trachomatis are also covered. A discussion of the various degrees of protection offered by different forms of contraception encourages use of barrier methods and oral contraceptives for teenagers as well as postponement of sexual activity. Detection, treatment, and vaccination against genital herpes are covered, along with diagnosing anogenital warts in children as either skin or genital wart virus types, and the relationship between human papillomavirus and cancer.

Humans↗

Demonstration of evolutionary differences between conserved antigenic epitopes in the minor nucleocapsid protein of human papillomavirus types 6b, 16 and 18.

We studied human papillomavirus (HPV) minor nucleocapsid protein (L2) by epitope scanning. Conserved antigenic epitopes identified by rabbit antiserum to bovine papillomavirus (BPV) were revealed in HPV-6b (amino acids, aa, 196-205); HPV-16 (aa:s 376-85) and HPV-18 (aa:s 221-230). L2 proteins. The first two epitopes were situated in hydrophilic regions of the proteins. Aligning the aa-sequences that corresponded to the epitopes with the total L2 sequences of BPV and HPV1a revealed consensus motifs between BPV, HPV1a and the reactive HPV type. In the non-reactive types amino acid alterations were noted. Mismatch between HPV1a sequences and the corresponding HPV-6b and HPV-16, HPV-6b and HPV-18, and HPV-16 and HPV-18 sequences suggests that the alterations may have evolved to facilitate immune surveillance of the genital HPV types.

Amino Acid Sequence↗

Association between vaginal douching and acute pelvic inflammatory disease.

The vaginal douching habits of 100 consecutive municipal hospital patients with verified pelvic inflammatory disease (cases) were compared with those of 762 randomly selected controls (random controls) and 119 women thought to have pelvic inflammatory disease but in whom the diagnosis was not confirmed by laparoscopy and/or endometrial biopsy specimen (internal controls). Because patients had been symptomatic for no more than 3 weeks, current douching was arbitrarily defined as any douching during the previous 2 months. Current douching was more common among those with pelvic inflammatory disease than among random controls or internal controls. Among current douchers, pelvic inflammatory disease was significantly related to frequency of douching. For example, when cases were compared with random controls, those who douched three or more times per month were 3.6 times more likely than those who douched less than once per month to have confirmed pelvic inflammatory disease. A logistic regression model was used to adjust for demographic, behavioral, and other possible confounding variables. Even after adjustments, douching during the previous 2 months remained associated with pelvic inflammatory disease. These data suggest that among these women vaginal douching may be a risk factor for pelvic inflammatory disease.

Acute Disease↗

Decreased risk of symptomatic chlamydial pelvic inflammatory disease associated with oral contraceptive use.

Studies have shown that oral contraceptive use may protect against pelvic inflammatory disease (PID), but it is not known whether oral contraceptives protect against the disease among women already infected with Chlamydia trachomatis or Neisseria gonorrhoeae. The relationship between oral contraceptive use and PID was analyzed in a case-control study of 141 women with verified PID and 739 randomly selected, sexually active women with no clinical evidence of the disease. Case and control subjects were stratified on the basis of infection with C trachomatis, N gonorrhoeae, or neither organism. Among women infected with C trachomatis alone, those with PID were less likely than control subjects to use oral contraceptives. The association was significant when oral contraceptive use was compared with nonuse (odds ratio, 0.22; 95% confidence interval, 0.08 to 0.64) and with noncontraception (odds ratio, 0.17; 95% confidence interval, 0.06 to 0.53) and remained so after adjusting for potential confounding variables by logistic regression analysis. Among women infected with N gonorrhoeae alone, no association was found between use of oral contraceptives and PID. These data suggest that oral contraceptive use protects against symptomatic PID among women infected with C trachomatis but not among those infected with N gonorrhoeae.

Adolescent↗

Adenocarcinoma of the uterine cervix.

In Finland, the incidence of cervical cancer has shown a decreasing tendency since the 1960s. The same trend, however, has not been noticed in the incidence of cervical adenocarcinoma. The reason for this is not known, although many studies have shown differences in the cause, epidemiology, and biology of the epidermoid and adenocarcinoma of the uterine cervix. A total of 106 new patients with cervical adenocarcinoma were treated at our institution from 1976 to 1980, which represents 20.4% of all cervical carcinomas treated. The mean age of the patients was 58.1 years (range, 29 to 82 years) and the peak incidence was in the group 60 to 69 years of age. Most of the patients were postmenopausal (71.7%) and the main symptom was abnormal vaginal bleeding (78.3%). The proportion of Stage I was 61.3%. Combined operative and radiation therapy was used in 74.5% of the patients. The overall 5-year survival rate was 65.1% (corrected 74.5%), which did not differ from that of patients with squamous cell carcinoma. The most significant prognostic factors were the size of the tumor, presence of pelvic lymph node metastases, and the stage of the disease.

Adenocarcinoma↗