Decreased plasma beta-carotene levels in women with uterine cervical dysplasias and cancer.
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Carotenoids↗
Biomedical subjects
S L Romney
Publications and source records attributed to S L Romney.
Detection of human papillomavirus deoxyribonucleic acid in exfoliated cervicovaginal cells as a predictor of cervical neoplasia in a high-risk population.
Specific types of human papillomavirus are currently implicated as etiologic agents of precancerous and cancerous lesions of the cervix. We have previously described the use of cervicovaginal lavage and molecular hybridization to detect human papillomavirus infections of the cervix. We report here the predictive value of this method of human papillomavirus detection to identify women with biopsy proved dysplastic and cancerous lesions of the cervix. One hundred ninety-one women from a city hospital colposcopy clinic underwent concurrent Papanicolaou smear, cervicovaginal lavage, and coloposcopically directed cervical biopsy. Human papillomavirus deoxyribonucleic acid was detected in 114 (59.7%) of these women. Of the positive results, human papillomavirus type 16 accounted for 23.7%, human papillomavirus type 18 for 10.5%, human papillomavirus type six or 11 for 6.2%, related human papillomavirus types for 52.6%, and 7.0% contained more than one type. The distribution of human papillomavirus types was similar in both women younger than 40 years of age and in older women. Eighty-nine of 128 (69.5%) women less than 40 years old with cervical lesions had positive findings of human papillomavirus, and 18 of 29 (62.1%) older women with cervical lesions had positive findings of human papillomavirus. Detection of human papillomavirus types 16 and 18 identified only 35 of 157 (22.3%) women with cervical lesions. The sensitivity of detecting all types of human papillomavirus as a predictor of a biopsy proved lesion (68.0%) was comparable with the sensitivity of cytologic examination alone (74.0%). However, human papillomavirus detection combined with the Papanicolaou smear provided an increased overall sensitivity of 89.3% (p less than 0.01). In fact, women either positive for human papillomavirus or having abnormal cytologic findings were 11.8 times more likely to have a biopsy proved cervical lesion than human papillomavirus-negative women with negative cytologic results (95% confidence interval for odds ratio: 5.3 to 26.6). We conclude that the sensitivity of cytologic examination plus human papillomavirus detection is superior to the use of either cytologic studies or human papillomavirus detection alone in identifying patients with cervical lesions.
Adolescent↗
Vaginal hydrolysis of retinyl acetate: increase in plasma retinol and retinol binding protein in women with cervical dysplasias.
We previously reported the clinical feasibility of a Phase I trial involving the topical administration of a RA gel applied cervicovaginally in women with mild or moderate cervical dysplasia. Now, we report hydrolysis and systemic absorption of the RA gel from the vagina. HPLC analysis of samples of residual gel obtained from the cervical canal after topical bolus application indicate that the RA undergoes prompt in vivo hydrolysis yielding retinol as a major metabolite. Venous blood samples of 41 subjects, who self-administered a RA gel, were analyzed for plasma retinol and RBP concentrations prior to and upon completion of a 7-day treatment course and upon return for follow-up examinations. An increase in both the concentrations of plasma retinol and RBP were detected after topical application of the RA gel. These elevated values receded after the gel administration was discontinued. No significant changes were observed in plasma retinol or RBP concentrations in placebo-treated subjects. The efficacy of RA as a chemopreventive agent in treating cervical dysplasias remains to be determined.
Diterpenes↗
Plasma reduced and total ascorbic acid in human uterine cervix dysplasias and cancer.
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Ascorbic Acid↗
Human papillomavirus infection of the cervix detected by cervicovaginal lavage and molecular hybridization: correlation with biopsy results and Papanicolaou smear.
Human papillomaviruses have previously been identified by molecular hybridization in the majority of dysplastic and cancerous lesions of the cervix. Since human papillomavirus types 16 and 18 have been strongly associated with cervical cancer, the identification of patients infected with these specific human papillomavirus types may provide useful prognostic information. We have developed a painless, noninvasive cervicovaginal lavage technique to collect exfoliated cervicovaginal cells, which can be reliably analyzed for the presence of human papillomavirus deoxyribonucleic acid by Southern blot analysis with the use of deoxyribonucleic acid cloned from human papillomaviruses 6, 11, 16, and 18. In a prospective study of 60 women referred to a colposcopy clinic for evaluation of abnormal Papanicolaou smears, we have detected human papillomavirus deoxyribonucleic acid in 16 of 17 (94%) women with a Class III (dysplasia) or IV (carcinoma in situ) Papanicolaou smear, five of 11 (45%) women with a Class II (atypical) Papanicolaou smear, and 10 of 34 (29%) women with a normal Papanicolaou smear. Detection of human papillomavirus deoxyribonucleic acid in cervicovaginal cells was indicative of a dysplastic cervical lesion in 19 of 20 (95%) patients irrespective of Papanicolaou smear results. We conclude that human papillomavirus deoxyribonucleic acid analysis in cervicovaginal cells is a sensitive method to detect dysplastic lesions of the cervix and may be useful in identifying patients with specific types of human papillomavirus infection, who are at risk to develop cervical cancer.
Biopsy↗
Human papillomaviruses of different types in precancerous lesions of the uterine cervix: histologic, immunocytochemical and ultrastructural studies.
In a prospective study of 34 women with abnormal Papanicolaou smears, biopsy and cervicovaginal lavage specimens were analyzed for the presence of human papillomaviruses (HPVs) by Southern blot analysis and probes for HPVs 6, 11, 16, and 18. In 22 of the 23 patients with cervical lesions (96%), HPV DNA was identified in one or more specimens. All patients in whom HPV DNA was found had either koilocytotic or dysplastic lesions on biopsy or Papanicolaou smear. Immunocytochemical demonstration of HPV in biopsy samples was associated with the presence of large amounts of HPV DNA and with the ultrastructural identification of viral particles. The presence of HPV DNA in cervical biopsy specimens was limited to discrete geographic areas of the cervix with histologic abnormalities. Although HPV 16 and other related HPV types were found in all cases of severe cervical intraepithelial neoplasia, the type of HPV present in a given specimen could not be predicted on the basis of morphologic, immunocytochemical, or electron microscopic findings. It is concluded that virtually all dysplastic lesions of the cervix contain HPV DNA, that HPV is thus likely to be a major etiologic agent in the pathogenesis of cervical dysplasia, and that histopathologic features are not predictive of HPV type.
Antigens, Viral↗
Plasma vitamin C and uterine cervical dysplasia.
Plasma concentrations of vitamin C were determined in a case-control study of women (n = 80) who had sought a Papanicolaou test in the Bronx Municipal Hospital Center. Controls (n = 34) were women having negative cytologic tests, negative colposcopic findings, and no known gynecologic dysfunction. Cases (n = 46) were defined as women who had either one positive or two consecutive suspicious Papanicolaou smears in a 12-month period. The mean concentration of vitamin C in the plasma was significantly lower in the cases than in the controls (0.36 versus 0.75 mg/dl, p less than 0.0001). Cases were further stratified according to the histopathologic diagnosis. The data direct attention to a possible etiologic association of vitamin C in human cervical epithelial abnormalities. A clinical trial with vitamin C intervention is suggested.
Adult↗
Chemoprevention of cervix cancer: Phase I-II: A feasibility study involving the topical vaginal administration of retinyl acetate gel.
A Phase I-II clinical trial has been conducted with a retinyl acetate (RA) gel applied cervicovaginally in women having a histopathologic lesion diagnosed as mild or moderate dysplasia. With informed consent, volunteer subjects were observed and followed with Pap smears and colposcopy in a standardized protocol involving a self-administered 7-day treatment course for three successive menstrual cycles. Varying dosages of RA including placebo, 3, 6, 9, and 18 mg per 6 g of an inert vehicle were employed. A total of 50 subjects were monitored for local and systemic side effects. No intolerable side effects or disturbing toxicity was reported or detected at any of these doses. With the 18-mg dosage, significant discomfort was reported by all women. Despite associated side effects and a considerable patient effort involved in carrying out the self-administration of the gel, a high level of compliance was achieved in this trial. It has been established that women will voluntarily participate in an intervention clinical trial to determine whether retinyl acetate is an alternative method of therapy of presumed precancerous lesions of the cervix. The analysis of the side effects of the gel at the various dosage concentrations favors the selection of the 9-mg dosage for a multicenter Phase III clinical trial to determine efficacy.
Colposcopy↗
Ultrastructure of normal, metaplastic, and abnormal human uterine cervix: use of montages to study the topographical relationship of epithelial cells.
The ultrastructure of the entire thicknesses of normal and abnormal human uterine cervical epithelia is studied with the use of slit-type grids. In four normal squamous epithelial specimens, basic similarities in the maturational sequence were apparent; however, significant variation in the progression of differentiation was also obvious. Because of this variation, it was not possible to always correlate cellular structure with cellular location within the epithelial strata. Four normal specimens containing combinations of squamous, columnar, and metaplastic cells show variations in the topographical relationships of these cells and stages in the transition of reserve to squamous cells in metaplastic zones. The presence of cells with features characteristic of squamous and columnar epithelia suggests a bipotentiality of reserve cells. Six abnormal specimens share several morphologic features, which usually, but not regularly, vary quantitatively with the extent of abnormality. Because of the inconsistent gradation of cellular features with lesion severity, it was essential that numerous ultrastructural parameters be considered in order to evaluate the extent of abnormality. Cellular features peculiar to individual specimens include edema, keratinization, phagocytic squamous cells, and cells similar in appearance to koilocytes described in condylomas. Electron micrograph montages of extensive unobstructed areas of normal and abnormal cervices and higher-magnification micrographs of cell components provide improved documentation of the variation in morphology of normal and abnormal epithelia. Use of montages also results in a clear view of ultrastructural changes accompanying the transition from normal to abnormal cervical epithelium.
Basement Membrane↗
Influence of vitamin A on cervical dysplasia and carcinoma in situ.
A case-control study was undertaken to determine the dietary intake of vitamin A in women having abnormal uterocervical cytology. The study groups (87 cases and 82 controls) were drawn from a population of women who received a screening Pap test in the ambulatory health care section of a large municipal hospital center. A subset of cases (with abnormal cytology) were matched to controls for age, ethnicity, socioeconomic status, and parity. Nutrient intake and retinol binding protein concentrations were determined; epidemiological data were also obtained. It was found that the subset of cases with severe dysplasia or carcinoma in situ (CIS) were more likely to have a total dietary vitamin A intake below the pooled median (3,450 IU) and/or a beta-carotene intake below the pooled median (2,072 IU) than were normal controls (p less than 0.05 and p less than 0.025, respectively). Odds ratios revealed approximately a 3-fold greater risk for severe dysplasia or CIS in women with lowered vitamin A or beta-carotene intake. In addition, retinol binding protein was either absent or undetectable in 78.8% of the dysplastic tissue samples, versus 23.5% of the normal tissue samples (p less than 0.005).
Adolescent↗
The effect of maternal glucose administration upon fetal myocardial glycogen change during acute blood loss in the term pregnant dog.
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Animals↗
Materno-fetal biochemical, circulatory and pathological changes following experimentally-induced uremia in the pregnant dog.
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Animals↗
Changes in fetal myocardial glycogen during hypoxia induced by maternal acute hemorrhagic shock.
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Animals↗
Urinary cyclic nucleotides and the cytopathology of human uterine cervical dysplasias.
Blinded urinary assays for cyclic guanosine 3':5'-monophosphate (cGMP) and cyclic adenosine 3':5'-monophosphate (cAMP) were performed on 49 subjects with documented abnormal cervical cytology and 21 control subjects with normal cytology. A significant difference in the mean cGMP:cAMP ratios between the case and control groups was found. A significantly greater proportion of women with cytological abnormalities had a cGMP:cAMP ratio above the 0.2 level (p less than 0.001). Cases treated surgically for severe dysplasia or carcinoma in situ of the cervix revealed a significant postsurgical fall in the cGMP:cAMP ratios (p less than 0.025). The possibility of utilizing urinary ratios of cyclic nucleotides as an objective index in the detection, monitoring of progression, and therapy of preneoplastic cervical lesions is discussed.
Carcinoma in Situ↗
Retinoids and the prevention of cervical dysplasias.
Women with abnormal cytology were matched with normal control subjects for age, parity, ethnicity, and socioeconomic class and participated in a blind case-control study focused on the role of nutrition in cervical dysplasia. Sucrose gradient ultracentrifugation studies for determination of the presence and concentration of the binding proteins for retinol and retinoic acid were performed on colposcopic biopsy tissue specimens. The nutritional survey revealed statistically significant differences for vitamins A and C and beta carotene. Retinol binding protein was absent or minimally detectable and inversely related to the severity of the dysplasia. It is proposed that a double-blind clinical trial be conducted to evaluate whether retinoids may pharmacologically inhibit, arrest, or reverse cervical dysplasia.
Ascorbic Acid↗
Dietary vitamin C and uterine cervical dysplasia.
A case-control study of women with cervical abnormalities identified through Pap smears, was conducted in the Bronx, New York, to explore the relationship between nutritional intake and cervical dysplasia. Nutrient intake was estimated from computer analysis of three-day food records and 24-hour recall for 169 study participants (87 cases, 82 controls), including a subset of 49 pairs matched for age, race and parity. Mean vitamin C intake per day from three-day food record for controls was 107 mg, compared to 80 mg for cases (p less than 0.01). Analysis of matched pairs showed similar results; 29% of cases compared to 3% of controls in matched subset had vitamin C intake less than 50% of the recommended daily allowance, yielding a ten-fold increase in risk of cervical dysplasia as estimated by odds ratio (p less than 0.05). Younger age, greater frequency of sexual intercourse and younger age at first intercourse were associated with higher risk of cervical dysplasia. Multiple logistic analyses indicated that low vitamin C intake is an independent contributor to risk of severe cervical dysplasia when age and sexual activity variables are controlled. Approximately 35% of US women in their reproductive years have daily vitamin C intake below 30 mg, and 68% have vitamin C intake below 88 mg. If other studies confirm these findings, it may be important to explore a possible protective role of supplementary vitamin C for women at high risk of cervical cancer.
Adolescent↗
Sex difference in cellular retinol- and retinoic acid-binding proteins in human colon adenocarcinomas.
Human colon adenocarcinomas and adjacent non-cancerous, normal colon from the same patient were assayed for the presence and amounts of cellular binding proteins for retinol (CRBP) and retinoic acid (CRABP) by sucrose gradient analysis. In male patients, the mean concentrations of both CRBP and CRABP in the colon cancers were statistically significantly higher than in the adjacent normal colon. By contrast, in female colon cancers, the mean levels for both binding proteins were reduced approximately 2-fold, compared to the concentrations in the adjacent normal colon. These findings reveal an unexpected sex difference in the binding proteins for retinol and retinoic acid in human colon malignancies.
Adenocarcinoma↗
Cellular binding proteins for vitamin A in human carcinomas and in normal tissues.
Blinded analyses of the concentrations of binding proteins for retinol and retinoic acid (CRABP) in homogenates of cancer and normal tissue aliquots obtained from human cervix, endometrium, ovary, breast, and lung were carried out by the sucrose gradient ultracentrifugation technique. In carcinomas of the cervix and endometrium, CRABP mean values of 50.4 and 123.2 pmol/g tissue, respectively were detected. Such concentrations represent a 3- and 4-fold increase over the mean values of CRABP in the normal cervix (16.9 pmol/g) and normal endometrium (30.8 pmol/g), respectively. In carcinomas of the ovary, the mean CRABP level was 128.6 pmol/g compared to the maximal mean value of less than or equal to 0.46 pmol/g in the normal ovary. Elevated levels of CRABP were also found in breast and lung carcinomas compared to the amounts detected in the same patient in normal tissue aliquots of the same organ. The differences between CRABP concentrations in cervical, endometrial, ovarian, and breast carcinomas and those in normal tissue are statistically significant. In contrast, cellular retinol-binding protein concentrations were reduced in the endometrial, ovarian, breast, and lung carcinomas compared to normal tissues. There were no significant differences between the log-mean concentrations of cellular retinol-binding proteins in the cytosols from tissue aliquots of carcinoma of the cervix and those in the cytosols from tissue aliquots of normal cervix.
Carcinoma↗