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R H Kaufman

Publications and source records attributed to R H Kaufman.

At least 19 recordsLinked to original sources
PubMed2001

Infertility among women exposed prenatally to diethylstilbestrol.

Although it is well established that women exposed to diethylstilbestrol in utero have an increased risk of spontaneous abortion, ectopic pregnancy, and preterm delivery, it is not known whether they also have an increased risk of infertility. The authors assessed this question in data from a collaborative follow-up study of the offspring of women who took diethylstilbestrol during pregnancy. In 1994, 1,753 diethylstilbestrol-exposed and 1,050 unexposed women from an ongoing cohort study (National Cooperative Diethylstilbestrol Adenosis Study and Dieckmann cohorts) provided data on difficulties in conceiving and reasons for the difficulty. Age-adjusted relative risks were computed for the association of diethylstilbestrol exposure with specific types of infertility. A greater proportion of exposed than unexposed women were nulligravid (relative risk (RR) = 1.3, 95% confidence interval (CI): 1.1, 1.5), and a greater proportion had tried to become pregnant for at least 12 months without success (RR = 1.8, 95% CI: 1.6, 2.1). Diethylstilbestrol exposure was significantly associated with infertility due to uterine and tubal problems, with relative risks of 7.7 (95% CI: 2.3, 25) and 2.4 (95% CI: 1.2, 4.6), respectively. The present findings indicate that diethylstilbestrol-exposed women have a higher risk of infertility than do unexposed women and that the increased risk of infertility is primarily due to uterine or tubal problems.

Adult↗
PubMed2001

Cancer risk in men exposed in utero to diethylstilbestrol.

BACKGROUND: An association between prenatal diethylstilbestrol (DES) exposure and cancer in men, especially testicular cancer, has been suspected, but findings from case-control studies have been inconsistent. This study was conducted to investigate the association between prenatal DES exposure and cancer risk in men via prospective follow-up. METHODS: A total of 3613 men whose prenatal DES exposure status was known were followed from 1978 through 1994. The overall and site-specific cancer incidence rates among the DES-exposed men were compared with those of the unexposed men in the study and with population-based rates. The relative rate (RR) was used to assess the strength of the association between prenatal DES exposure and cancer development. All statistical tests were two-sided. RESULTS: Overall cancer rates among DES-exposed men were similar to those among unexposed men (RR = 1.07; 95% confidence interval [CI] = 0.58 to 1.96) and to national rates (RR = 0.99; 95% CI = 0.65 to 1.44). Testicular cancer may be elevated among DES-exposed men, since the RRs for testicular cancer were 3.05 (95% CI = 0.65 to 22.0) times those of unexposed men in the study and 2.04 (95% CI = 0.82 to 4.20) times those of males in the population-based rates. The higher rate of testicular cancer in the DES-exposed men is, however, also compatible with a chance observation. CONCLUSIONS: To date, men exposed to DES in utero do not appear to have an increased risk of most cancers. It remains uncertain, however, whether prenatal DES exposure is associated with testicular cancer.

Carcinogens↗
PubMed2001

Adenovirus-mediated thymidine kinase gene therapy in combination with topotecan for patients with recurrent ovarian cancer: 2.5-year follow-up.

OBJECTIVE: Patients with recurrent ovarian cancer were treated intraperitoneally (ip) with a replication-deficient recombinant adenovirus (ADV) containing the herpes simplex virus thymidine kinase gene. Vector delivery was followed by intravenous administration of an antiherpetic prodrug and a topoisomerase I inhibitor. METHODS: Ten patients with stage IIIc epithelial ovarian cancer underwent secondary debulking to < or =0.5 cm residual tumor. Patients with normal ip flow received delivery of ip ADV. Two patients each were treated on dose level 1 (2 x 10(10) vector particles), dose level 2 (2 x 10(11)), and dose level 3 (2 x 10(12)); four patients were on dose level 4 (2 x 10(13)). Acyclovir and topotecan were started 24 h after vector delivery. Five patients underwent second-look surgery about 4 weeks after application of gene therapy (GT). RESULTS: At the time of the second-look surgery, two out of five patients were free of tumor. Four weeks after GT none of the peritoneal biopsies showed residual vector DNA. Patients pretreated with an average of three different chemotherapeutic drugs and two different chemotherapy regimens had a median overall survival (OS) of 18.5 months. Three patients are still alive 30, 30, and 31 months after GT. CONCLUSION: With the combination of secondary optimal debulking, GT, and topotecan, median OS was about one-third longer than in previously reported second-and third-line trials. Survival was comparable to that of patients of other studies with secondary cytoreductive surgery in combination with chemotherapy.

Acyclovir↗
PubMed2001

Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States).

OBJECTIVES: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES. METHODS: A cohort comprising 3,899 DES-exposed and 1,374 unexposed daughters was followed for 13 years (1982 1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates. RESULTS: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis. CONCLUSIONS: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.

Carcinoma, Squamous Cell↗
PubMed2001

Treating vulvar vestibulitis with electromyographic biofeedback of pelvic floor musculature.

OBJECTIVE: To evaluate the effectiveness of electromyographic biofeedback of pelvic floor musculature in the management of patients with moderate to severe vulvar vestibulitis syndrome. STUDY DESIGN: Twenty-nine patients with moderate to severe vulvar vestibulitis syndrome were included in this study. Each patient was given a computerized electromyographic assessment of pelvic floor muscles. She was then provided with a portable electromyographic home trainer biofeedback device, and specific instructions were given to perform biofeedback-assisted pelvic floor muscle rehabilitation exercises. The patients received monthly evaluations of the pelvic floor muscles to ensure and motivate compliance and to monitor improvement and symptom changes. Patients were evaluated on a monthly basis for vestibulodynia and dyspareunia. RESULTS: Fifteen of the 29 treated patients (51.7%) demonstrated markedly decreased introital tenderness, and 14 of them (93.3%) were able to resume sexual activity without discomfort. Nine patients (31.0%) demonstrated a significant decrease in introital tenderness and pain, and six of the nine (66.7%) resumed sexual activity. Thus, 20 of the 29 women (69%) became sexually active. Following completion of treatment, 24 (88.9%) reported negligible or mild pain. Five of the 29 did not show any significant improvement, and none of them were able to resume sexual activity. Within six months of the start of therapy, 90% ultimately resuming sexual activity had done so. CONCLUSION: Electromyographic biofeedback of pelvic floor musculature is an effective approach to vulvar vestibulitis.

Adult↗
PubMed2000

Papillomavirus detection: demographic and behavioral characteristics influencing the identification of cervical disease.

OBJECTIVE: This study was undertaken to assess the association between detection of high-risk types of human papillomavirus and various demographic and behavioral characteristics and to further relate this association to cervical histopathologic findings. STUDY DESIGN: A total of 1007 patients with a Papanicolaou test result reported as high-grade squamous intraepithelial lesion or with 2 results reported as atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion were referred from city and county clinics to a colposcopic clinic. All women had a cervical smear obtained, underwent colposcopically directed biopsy and endocervical curettage, and had a specimen taken for human papillomavirus deoxyribonucleic acid detection by polymerase chain reaction. Demographic information was obtained from each patient. RESULTS: Human papillomavirus deoxyribonucleic acid was identified in 655 (66%) of the specimens. High-risk human papillomavirus types (16, 18, 31, 33, and 35) were detected in 463 (70.7%) of these specimens. The prevalence of evidence of human papillomavirus (koilocytosis) and grade 1 cervical intraepithelial neoplasia in the biopsy specimen decreased significantly with age, whereas the prevalence of grade 2 or 3 cervical intraepithelial neoplasia in the biopsy specimen increased with age. There was a significant age-dependent decreasing trend in detection of high-risk human papillomavirus deoxyribonucleic acid among women who had human papillomavirus-associated changes, grade 1 cervical intraepithelial neoplasia, and grade 2 or 3 cervical intraepithelial neoplasia in the biopsy specimen. The prevalences of high-risk human papillomavirus among patients with grade 1 cervical intraepithelial neoplasia and grade 2 or 3 cervical intraepithelial neoplasia were similar, and both were significantly higher than among women with no evidence of cervical intraepithelial neoplasia or koilocytosis in the biopsy specimen. Risk factors associated with grade 2 or 3 cervical intraepithelial neoplasia were different from those associated with human papillomavirus-associated changes and with grade 1 cervical intraepithelial neoplasia. CONCLUSION: The detection of high-risk human papillomavirus was age-dependent for all histologic categories. Patients with grade 2 or 3 cervical intraepithelial neoplasia had a prevalence of high-risk human papillomavirus that was similar to that among women with grade 1 cervical intraepithelial neoplasia but significantly higher than that among women whose biopsy specimens appeared normal or demonstrated only the presence of human papillomavirus-induced changes (koilocytosis). This suggests that separation of human papillomavirus-associated changes only from grade 1 cervical intraepithelial neoplasia may be of significance in tissue diagnosis.

Adolescent↗
PubMed2000

Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring.

OBJECTIVE: To evaluate long-term pregnancy experiences of women exposed to diethylstilbestrol (DES) in utero compared with unexposed women. METHODS: This study was based on diethylstilbestrol-exposed daughters, the National Collaborative Diethylstylbistrol Adenosis cohort and the Chicago cohort, and their respective nonexposed comparison groups. Subjects who could be traced were sent a detailed questionnaire in 1994 that contained questions on health history, including information on pregnancies and their outcomes. We reviewed 3373 questionnaires from exposed daughters and 1036 questionnaires from unexposed women. RESULTS: The response rate was 88% among exposed and unexposed women. Diethylstilbestrol-exposed women were less likely than unexposed women to have had full-term live births and more likely to have had premature births, spontaneous pregnancy losses, or ectopic pregnancies. Full-term infants were delivered in the first pregnancies of 84.5% of unexposed women compared with 64. 1% of exposed women identified by record review (relative risk [RR] 0.76, confidence interval [CI] 0.72, 0.80). Preterm delivery of first births occurred in 4.1% of unexposed compared with 11.5% of exposed women, and ectopic pregnancies in 0.77% of unexposed compared with 4.2% of exposed women. Spontaneous abortion was reported in 19.2% of DES-exposed women compared with 10.3% in control women (RR 2.00, CI 1.54, 2.60). According to complete pregnancy histories (many women had more than one pregnancy), preterm births were more common in DES-exposed women (19.4% exposed versus 7.5% unexposed (RR 2.93 CI 2.23, 3.86). Second-trimester spontaneous pregnancy losses were more common in DES-exposed women (6.3% versus 1.6%; RR 4.25, CI 2.36, 7.66). More first-trimester spontaneous abortions occurred in DES-exposed women than in controls (RR 1.31, CI 1.13, 1.53), and DES-exposed women had at least one ectopic pregnancy more often than unexposed women (RR 3.84, CI 2.26, 6.54). CONCLUSION: Pregnancy outcomes in DES-exposed women were worse than those in unexposed women.

Abortion, Spontaneous↗
PubMed2000

Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer.

INTRODUCTION: Patients with recurrent ovarian cancer were treated with a replication-deficient recombinant adenovirus containing the herpes simplex virus thymidine kinase gene administered intraperitoneally (i.p.) followed by administration of an anti-herpetic prodrug and topotecan. MATERIALS AND METHODS: A total of 10 patients with stage IIIc epithelial ovarian cancer underwent secondary debulking to < or =0.5 cm residual tumor. Patients with normal i.p. flow received i.p. delivery of adenovirus. Two patients each were treated on dose level 1 (2 x 10(10) vector particles (VP)), dose level 2 (2 x 10(11) VP), and dose level 3 (2 x 10(12) VP); four patients were treated on dose level 4 (2 x 10(13) VP). Acyclovir and topotecan were started 24 hours after vector delivery. RESULTS: No patient treated at any dose level incurred unanticipated toxic effects, and all side effects resolved. The most common adverse event was myelosuppression: grade 3 or 4 thrombocytopenia with grade 2-4 anemia in three patients and grade 3 or 4 neutropenia in eight patients. Three patients developed thrombocytosis and three patients had a mild elevation of serum glutamic pyruvic transaminase/alanine aminotransferase. Temperature elevations that were not associated with detectable infection occurred in two patients. DISCUSSION: I.p. delivery of adenoviral vector with concomitant topotecan chemotherapy was well tolerated without significant lasting toxicities. Side effects were independent of the dose of adenoviral vector.

Acyclovir↗
PubMed2000

Endocervical curettage in evaluating abnormal cervical cytology.

OBJECTIVE: To determine the role of endocervical curettage (ECC) in the evaluation of women with abnormal cervical cytology and following treatment for cervical intraepithelial neoplasia. STUDY DESIGN: A retrospective chart review using the records of 2,126 patients who were seen at the Colposcopy Clinic, Baylor College of Medicine, between 1980 and 1995. All patients were referred because of an abnormal cervical smear and underwent repeat Pap smear, colposcopic examination in each case with biopsies as indicated, endocervical curettage and treatment, consisting of either cryotherapy, laser vaporization or a LOOP electrosurgical excision procedure. Following treatment, Pap smears were performed on a scheduled basis, and ECC was performed annually. RESULTS: The ECC was negative in 1,849 (87%) of the women. It was abnormal in 33% of women with unsatisfactory colposcopy and 10% of women with satisfactory colposcopy. ECC was abnormal in 21% of patients with a negative biopsy result and 42% of patients who did not have a biopsy performed. There was a significant increase in abnormal ECC results with increasing age. ECC had a high positive predictive value for ectocervical disease (86%) and a high negative predictive value for endocervical disease (90%). One year following treatment, < 4% of patients with a negative cervical smear had a high grade lesion detected on ECC. CONCLUSION: The use of ECC is helpful in detecting disease missed by routine colposcopy and biopsy and is most likely to detect ectocervical disease rather than true endocervical disease. Following treatment, ECC does not appear to be significantly more reliable than the Pap smear in detecting the presence of significant residual disease.

Adolescent↗
PubMed1999

Is human papillomavirus testing of value in clinical practice?

The objective of this review was to evaluate the current status of human papillomavirus testing in predicting the presence of high-grade or invasive disease in the cervix in women with Papanicolaou smears reported as atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion. This is a review of many of the studies already published evaluating the utility of human papillomavirus testing as part of the triage for patients whose Papanicolaou smears were reported as ASCUS or low-grade squamous intraepithelial lesion. Two triage approaches for follow-up of such patients are presented, and recommendations are made as to which is most cost-effective and safe. Data related to human papillomavirus testing were obtained with both currently available commercial kits for detection of high-risk human papillomavirus and the polymerase chain reaction. There was variation in results reported, possibly related to populations studied. The approach to management by cytologic screening and colposcopy, when indicated, appeared over the long term to be equal to human papillomavirus testing. In our opinion current human papillomavirus testing is of little clinical use to the practitioner. Its use should be limited to appropriately designed and implemented research studies.

Cervix Uteri↗
PubMed1999

A simple, inexpensive device for teaching the loop electrosurgical excision procedure.

OBJECTIVE: To develop an inexpensive and practical inanimate model to teach the loop electrosurgical excision procedure in a resident clinic. TECHNIQUE: A vaginal speculum is inserted into one end of a cardboard tube. At the opposite end, a piece of knockwurst sausage is inserted into the cardboard tube. A grounding pad is attached to the distal end of the sausage. The teaching session proceeds using a colposcope or direct visualization. After the training session, the excised and uncut portions of sausage can be examined. EXPERIENCE: Faculty found this inanimate model an excellent way to teach residents how to use the loop electrode, and the resident staff appreciated its merits as a useful prelude to treating cervical disease in women. The house staff adapted to the confines of the vagina and transferred skills acquired from working with the cardboard tube, where instruction and constructive criticism can be given without the presence of apprehensive patients. CONCLUSION: A simple, inexpensive, inanimate model has been developed to teach the loop electrosurgical excision procedure. The materials required to construct it are available to any colposcopy clinic.

Electrosurgery↗
PubMed1999

Butoconazole nitrate 2% for vulvovaginal candidiasis. New, single-dose vaginal cream formulation vs. seven-day treatment with miconazole nitrate. Gynazole 1 Study Group.

OBJECTIVE: To compare the safety and efficacy of a single vaginal dose of a butoconazole nitrate 2% bioadhesive, sustained-release cream* (butoconazole 1-BSR) with a seven-day schedule of miconazole nitrate vaginal cream 2% (miconazole 7). STUDY DESIGN: The clinical trial was conducted according to a randomized, parallel, investigator-blind, multicenter study design. The patients self-administered the respective creams to the posterior vaginal fornix. Two hundred twenty-three patients started the trial and were analyzed for safety. A total of 205 patients qualified for efficacy analysis, 101 receiving butoconazole 1-BSR and 104 using miconazole 7. Patients receiving butoconazole 1-BSR inserted one applicator full of medication once. Those assigned to receive miconazole 7 inserted one applicator full daily for seven days. Patients were evaluated 7-10 and 30 days after completion of therapy. RESULTS: Butoconazole 1-BSR rapidly relieved the signs and symptoms of vulvovaginal candidiasis. The proportion of patients with severe symptoms declined from the pretreatment 20% to 6% on the 1st day, to 3% on the 4th day, and to 2-1% on the 5th-7th day after single-dose application. Eight to ten days after treatment completion, clinical symptoms regressed in 92%, and fungal cultures were negative in 87% of patients. At the 30-day posttreatment visit, 88% of patients remained clinically cured, and 74% had negative fungal cultures. In the miconazole 7 group, the proportion of patients with severe symptoms declined from 23% to 19% after the first dose; thereafter, symptom relief proceeded more rapidly. Eight to ten days after treatment completion, clinical symptoms regressed in 92% and fungal cultures were negative in 87% of patients. At the 30-day follow-up examination, 86% patients were clinically cured, and 77% were culture negative. After single-dose butoconazole 1-BSR, severe symptoms receded faster than after the first dose of miconazole 7, and the difference was statistically significant (P = .01). In all other efficacy parameters, the differences between the two groups were not statistically significant. Neither treatment regimen caused significant adverse events. CONCLUSIONS: This clinical trial demonstrated that butoconazole 1-BSR is an effective and safe alternative to longer-term therapy with miconazole nitrate (seven days) for vulvovaginal candidiasis.

Administration, Topical↗
PubMed1998

Expression of ras, c-myc, and p53 proteins in cervical intraepithelial neoplasia.

BACKGROUND: The development of cervical carcinoma is influenced by multiple factors, including the presence of certain high risk types of human papillomavirus. The purpose of the current study was to investigate possible cooperating genetic changes by examining the expression of p53, p62 myc, and p21 ras in cervical biopsy specimens. METHODS: Three hundred and ninety-five cervical biopsy specimens representing normal through high grade cervical intraepithelial neoplasia (CIN) were screened by immunohistochemistry for expression of p53, p62myc, and p21ras. RESULTS: Neither the proportion of tissues staining positive for a given protein nor the staining patterns within the epithelial layers differed significantly among normal or CIN biopsy samples. However, grade specific nuclear staining of p21ras was found in the cells of 10 lesions that were classified as CIN I by histology. CONCLUSIONS: These results established the normal distribution and expression patterns of p53, p62myc, and p21ras within 395 cervical biopsy samples representing normal through CIN III histology. The expression of these proteins (e.g., staining intensity and layer of epithelium staining positive) is similar in normal tissues and those demonstrating all grades of CIN.

Carcinoma in Situ↗
PubMed1998

Cancer risk in women exposed to diethylstilbestrol in utero.

CONTEXT: The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero. OBJECTIVE: To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up. DESIGN: A cohort study with mailed questionnaires and medical record review of reported cancer outcomes. PARTICIPANTS: A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s. MAIN OUTCOME MEASURES: Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters. RESULTS: To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result. CONCLUSIONS: Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years.

Adenocarcinoma, Clear Cell↗
PubMed1998

Is human papillomavirus testing an effective triage method for detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia?

OBJECTIVE: Our purpose was to assess the usefulness of the polymerase chain reaction assay for detection of human papillomavirus infection for prognostic value in the triage strategies for high-grade (grade 2 or 3) cervical intraepithelial neoplasia in women referred for colposcopy after abnormal Papanicolaou smears. STUDY DESIGN: A total of 1007 women referred to a colposcopic clinic providing care for an indigent population were studied. Four hundred fifty-four women were referred after two Papanicolaou smears reported as atypical squamous cells of undetermined significance or low grade-squamous cervical intraepithelial lesion, and 553 were referred after a single smear reported as high-grade squamous intraepithelial lesion. All women had a cervical smear, colposcopy-directed biopsy, and endocervical curettage performed. A sample for human papillomavirus deoxyribonucleic acid detection by polymerase chain reaction was obtained. RESULTS: High-risk human papillomavirus types were detected in 463 (46%) of 1007 women studied. There was a significant increase of the frequency of high-risk human papillomavirus by the increasing severity of biopsy findings ranging from 32.7% in women without cervical intraepithelial neoplasia on biopsy to 60% in women having grade 2 or 3 on the biopsy specimen. Women having a negative Papanicolaou smear found to have high-risk human papillomavirus deoxyribonucleic acid at the time of colposcopy had a significantly higher rate of grade 2 or 3 cervical intraepithelial neoplasia on the biopsy specimen than did women without high-risk human papillomavirus. There was no such difference observed in women with a cytologic finding of low- or high-grade squamous intraepithelial lesions at the time of colposcopy. The polymerase chain reaction assay appears to be more sensitive than the commercial human papillomavirus profile test. The positive predictive value for grade 2 or 3 cervical intraepithelial neoplasia of both tests was similar (21.7% and 22.8%, respectively). CONCLUSION: The human papillomavirus is associated with high-grade cervical intraepithelial neoplasia, but the screening for human papillomavirus deoxyribonucleic acid does not have prognostic value in women reported as having atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions on two precolposcopy Papanicolaou smears.

Biopsy↗