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Biomedical subjects

R H Kaufman

Publications and source records attributed to R H Kaufman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Analysis of atypical squamous (glandular) cells of undetermined significance smears by neural network-directed review.

OBJECTIVE: The objective of this study was to evaluate the value of neural network-directed review of smears determined to contain atypical squamous (glandular) cells of undetermined significance to identify those cases most likely to be associated with cervical intraepithelial neoplasia. METHODS: One hundred sixty smears reported as atypical squamous (glandular) cells of undetermined significance on patients having colposcopy and directed biopsy within 1 year of the smear were identified. The smears were subjected to a neural network-directed review and classified according to findings on this review. The latter findings were related to those obtained on cervical biopsy. RESULTS: One hundred sixty smears originally reported as atypical squamous (glandular) cells of undetermined significance were subjected to neural network-directed review. The smears were upgraded in 20.6% of cases. Ninety-one patients were found to have normal biopsies, and 69 had biopsies reported as abnormal. Of the smears in patients with abnormal biopsies, 37.7% were upgraded, whereas only 7.7% of smears from those with normal biopsies were upgraded (P < .001). Nine patients were found to have cervical intraepithelial neoplasia-3 on biopsy. Six of the nine smears (66.7%) taken on these patients were upgraded. CONCLUSION: Neural network-directed analysis of smears conventionally diagnosed as atypical squamous (glandular) cells of undetermined significance will reveal findings suggesting a squamous intraepithelial lesion in a significant number of cases. This approach requires further study because it is a relatively cost-effective means of triaging patients with a cytologic diagnosis of atypical squamous (glandular) cells of undetermined significance.

Adolescent↗
PubMed1998

Environmental endocrine modulators and human health: an assessment of the biological evidence.

Recently, a great deal of attention and interest has been directed toward the hypothesis that exposure, particularly in utero exposure, to certain environmental chemicals might be capable of causing a spectrum of adverse effects as a result of endocrine modulation. In particular, the hypothesis has focused on the idea that certain organochlorine and other compounds acting as weak estrogens have the capability, either alone or in combination, to produce a variety of adverse effects, including breast, testicular and prostate cancer, adverse effects on male reproductive tract, endometriosis, fertility problems, alterations of sexual behavior, learning disability or delay, and adverse effects on immune and thyroid function. While hormones are potent modulators of biochemical and physiological function, the implication that exposure to environmental hormones (e.g., xenoestrogens) has this capability is uncertain. While it is reasonable to hypothesize that exposure to estrogen-like compounds, whatever their source, could adversely affect human health, biological plausibility alone is an insufficient basis for concluding that environmental endocrine modulators have adversely affected humans. Diethylstilbestrol (DES) is a potent, synthetic estrogen administered under a variety of dosing protocols to millions of women in the belief (now known to be mistaken) that it would prevent miscarriage. As a result of this use, substantial in utero exposure to large numbers of male and female offspring occurred. Numerous studies have been conducted on the health consequences of in utero DES exposure among the adult offspring of these women. There are also extensive animal data on the effects of DES and there is a high degree of concordance between effects observed in animals and humans. The extensive human data in DES-exposed cohorts provide a useful basis for assessing the biological plausibility that potential adverse effects might occur following in utero exposure to compounds identified as environmental estrogens. The effects observed in both animals and humans following in utero exposure to sufficient doses of DES are consistent with basic principles of dose response as well as the possibility of maternal dose levels below which potential non-cancer effects may not occur. Significant differences in estrogenic potency between DES and chemicals identified to date as environmental estrogens, as well as an even larger number of naturally occurring dietary phytoestrogens, must be taken into account when inferring potential effects from in utero exposure to any of these substances. The antiestrogenic properties of many of these same exogenous compounds might also diminish net estrogenic effects. Based on the extensive data on DES-exposed cohorts, it appears unlikely that in utero exposure to usual levels of environmental estrogenic substances, from whatever source, would be sufficient to produce many of the effects (i.e., endometriosis, adverse effects on the male reproductive tract, male and female fertility problems, alterations of sexual behavior, learning problems, immune system effects or thyroid effects) hypothesized as potentially resulting from exposure to chemicals identified to date as environmental estrogens.

Adult↗
PubMed1998

Lichen sclerosus. Therapy with clobetasol propionate.

OBJECTIVE: To assess the efficacy of treating lichen sclerosus with clobetasol propionate. STUDY DESIGN: A retrospective chart review of 81 consecutive symptomatic private practice and clinic patients with biopsy-proven lichen sclerosus were included. All subjects' punch biopsies, baseline histories and physical examinations were reviewed by the same examiner. Each subject's symptomatology and responses to previous treatment modalities were recorded. A standard regimen of 0.05% clobetasol propionate cream was initiated. Subjects were reevaluated at three months and asked to rate the improvement of symptoms. Follow-up examinations were conducted 6-12 months later on 36 subjects. Descriptive statistics and chi 2 analyses were performed. RESULTS: The mean age of subjects was 54 +/- 15.5 years (range, 15-86), and the average duration of treatment prior to clobetasol use was 6 +/- 6.9 years (range, 0.5-29). Twenty-seven subjects did not complete the study or were lost to follow-up. The average subject had tried 2.25 treatment modalities (range, 1-13). The most common symptoms were pruritus (98%) and irritation (61%), with complaints of burning and dyspareunia. Most subjects (76%) had labial involvement, with concomitant involvement of the clitoris (70%), perineum (68%) and perianus (32%). The majority (88%) of subjects had a primary lesion of white and crinkled tissue. With clobetasol, 77% of subjects had complete remission of symptoms, 18% had partial remission and 5% reported no change. A change in clinical appearance was noted for the complete-remission (32%) and partial-remission groups (46%). Twenty-two percent revealed no change. CONCLUSION: Clobetasol propionate cream is recommended for treatment of lichen sclerosus, with a 77% chance of complete remission of symptoms and a 47% chance of improvement in the clinical appearance of the vulva. Women may have to continue to use clobetasol as needed after finishing a base treatment course.

Administration, Topical↗
PubMed1997

Sterilization with fibrin sealant in a rabbit uterine horn model.

OBJECTIVE: This study investigated the effects of a fibrin sealant with or without coagulation in obliterating the tubal lumen at the uterotubal junction in rabbits. STUDY DESIGN: Twenty-three female rabbits were subjected to laparotomy and hysterotomy. They were randomly divided into four groups, and the fallopian tubes underwent different treatment: In group 1 (n = 14) both bipolar coagulation and the fibrin sealant were used. In group 2 (n = 10) only fibrin sealant without coagulation was used. In group 3 (n = 11) only coagulation was used. In group 4 (n = 10) no treatment was performed (control group). Two to three rabbits were euthanized on days 3 to 4, 7 to 11, 14 to 17, and 21 to 24 postoperatively. Both uterotubal junctions were excised, and step cross sections were obtained. The morphologic features including denuded epithelium with debris, submucosal fibrosis, hemorrhage, and fibrinoid matter in the tubal lumen and occluded lumen were observed. RESULTS: Tubal lumina were successfully occluded in 10 of 14 tubes (71.4%) in group 1. In groups 2 and 4 none of the tubes were occluded, and in group 3 only three tubes were partially occluded. The difference between group 1 and other groups was significant (p < 0.05). CONCLUSIONS: The effects of bipolar coagulation in enhancing the inflammatory reaction on the mucosa and scar formation induced by fibrin sealant at the uterotubal junction in the rabbit were demonstrated. This sterilization method with the use of fibrin sealant may be developed into an outpatient procedure in humans and may be a new method for female sterilization in the future.

Animals↗
PubMed1997

Human papillomavirus testing as triage for atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions: sensitivity, specificity, and cost-effectiveness.

OBJECTIVE: Our purpose was to evaluate the cost-effectiveness of the use of a Food and Drug Administration-approved human papillomavirus test in triaging patients with Papanicolaou smears showing atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion for colposcopy compared with an algorithm that used cytologic follow-up. STUDY DESIGN: Four hundred sixty-two women referred to our Colposcopy Clinic with a Papanicolaou smear report of atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion underwent repeat Papanicolaou smear, cervical colposcopy, directed cervical biopsy, and endocervical curettage. In addition, human papillomavirus testing by the Food and Drug Administration-approved HPV Profile (Digene Diagnostics, Silver Spring, Md.) test was done. A comparison of sensitivity, specificity, and cost-effectiveness of an algorithm determining the need for colposcopy on the basis of repeat cytologic testing versus an algorithm that incorporated repeat cytologic testing and human papillomavirus screening was done. The cost-effectiveness of both of these triage algorithms was also compared. RESULTS: As expected, high-risk human papillomavirus deoxyribonucleic acid was detected with greater frequency in relation to increasing severity of cervical intraepithelial neoplasia. In 268 women, the follow-up smear obtained in our clinic was reported as negative. High-risk human papillomavirus types were found in 23.5% of these women. In the human papillomavirus-negative women, 5.9% had grade 2 or 3 cervical intraepithelial neoplasia confirmed on cervical biopsy. In comparison, 20.6% of those with a positive result of the human papillomavirus test had grade 2 or 3 cervical intraepithelial neoplasia on biopsy (p < 0.001). Despite this difference, the sensitivity of a positive result of a high-risk human papillomavirus test in predicting the presence of grade 2 or 3 cervical intraepithelial neoplasia was only 52%. Among the women for whom a follow-up clinic Papanicolaou smear was reported as showing atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion, there was no difference in the frequency of biopsy-proved grade 2 or 3 cervical intraepithelial neoplasia between those women with a positive human papillomavirus test result and those with a negative test result. Colposcopy would have been recommended for 194 women because of a repeat clinic smear revealing atypical squamous cells of undetermined significance, a low-grade squamous intraepithelial lesion, or a high-grade squamous intraepithelial lesion, and in 21.6% of these grade 2 or 3 cervical intraepithelial neoplasia was shown on biopsy (sensitivity 63%, specificity 62%). Colposcopy would have been recommended for 180 women because high-risk human papillomavirus or a high-grade squamous intraepithelial lesion was detected at the clinic visit, and in 25% of this group grade 2 or 3 cervical intraepithelial neoplasia was shown on biopsy (sensitivity 67%, specificity 66%). Sensitivity and specificity were virtually identical for the two algorithms, but the cost of human papillomavirus testing was nearly double that of triage based on repeat cytologic testing alone ($692 vs $1246 per case). CONCLUSION: The Food and Drug Administration-approved HPV Profile test is not a cost-effective triage for patients referred with Papanicolaou smears reported as showing atypical squamous cells of undetermined significance or low-grade squamous lesions.

Algorithms↗
PubMed1997

Relevance of human papillomavirus screening in management of cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the utility of human papillomavirus detection in identifying women with abnormal Papanicolaou smears who can be safely followed up with cytologic study only, we conducted a study to determine the sensitivity, specificity, and negative and positive predictive values of a Food and Drug Administration-approved human papillomavirus test kit for detection of cervical intraepithelial neoplasia in colposcopically directed biopsy specimens. STUDY DESIGN: We enrolled women with abnormal Papanicolaou smears referred to a colposcopy clinic serving indigent patients. All 1128 women had a referral Papanicolaou smear, a clinic Papanicolaou smear, and a sample for human papillomavirus deoxyribonucleic acid test; 1075 underwent colposcopically directed biopsies and endocervical curettage. We used the HPV Profile kit for human papillomavirus testing. RESULTS: Of 486 women with low-grade squamous intraepithelial lesions on Papanicolaou smear, 35.4% had high-risk human papillomavirus deoxyribonucleic acid detected, and of 592 with high-grade lesions, 44.4% had high-risk human papillomavirus detected. Among 527 women with biopsy specimens showing cervical intraepithelial neoplasia and in 267 with cervical intraepithelial neoplasia grades 2 or 3, 38.7% and 56.2% had high-risk human papillomavirus deoxyribonucleic acid detected. However, the sensitivity of human papillomavirus deoxyribonucleic acid detection to identify biopsy-confirmed cervical intraepithelial neoplasia grades 2 or 3 was 55.7%, and the positive predictive value of the test was only 34.9%. CONCLUSION: Human papillomavirus appears to be causally associated with cervical cancer but human papillomavirus screening does not appear to be of value to identify women with abnormal Papanicolaou smears who can be safely followed up with cytologic study alone.

Adolescent↗
PubMed1996

In vivo gene therapy of ovarian cancer by adenovirus-mediated thymidine kinase gene transduction and ganciclovir administration.

Efficacy and toxicity of adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene followed by administration of ganciclovir were studied in vivo. A human epithelial ovarian cancer animal model was established in nude mice using the serous ovarian adenocarcinoma cell line Ov-ca-2774. Intraperitoneal (ip) injection of 1 x 10(8) Ov-ca-2774 cells resulted in tumor growth and formation of malignant ascites in all 15 animals. In a prospective randomized experimental design mice were treated 1, 3, or 7 days after ip injection of 1 x 10(8) cells with ip injection of 2 x 10(8), 6.7 x 10(8), or 2 x 10(9) pfu ADV.RSV-TK followed by administration of ganciclovir (10 microgram /ml, ip, bid) for 6 consecutive days. End points were survival and toxicity. Mice treated with GCV or HSV-TK alone died from 14.4 +/- 1.7 to 19.5 +/- 3.5 days after treatment as did untreated controls. No toxicity of ADV.RSV-TK was found up to 2 x 10(9) pfu (2 x 10(11) particles). The mice with the highest tumor burden treated with the lowest viral dose lived significantly longer than controls (P < 0.05). Median survival in all other groups of mice treated with ADV.RSV-TK plus GCV was even longer (P < 0.01). Treatment benefit was dependent on ADV/RSV-TK dose and tumor burden. Adenovirus-mediated thymidine kinase gene therapy is a realistic approach to ovarian cancer treatment that warrants investigation in the clinical setting.

Adenoviridae↗
PubMed1996

Atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion: diagnostic criteria and management.

Since institution of the Bethesda system for reporting cervical and vaginal smears, there has been an increase in the number of smears reported to demonstrate atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The cytologic changes associated with a smear reported to have these cells are discussed. It is apparent that the interpretation of the cellular changes defined as atypical squamous cells of undetermined significance are not clear and that there is a significant variation among cytopathologists as to the cytologic changes that should be incorporated under this classification. Data are presented on the frequency of this diagnosis in our laboratory and of the follow-up findings observed in a subgroup of patients whose smears were reported to demonstrated atypical squamous cells of undetermined significance. The cytologic and histopathologic changes observed with smears reported as demonstrating findings compatible with a low-grade squamous intraepithelial lesion are also discussed. A follow-up algorithm for the management of such patients is presented.

Cervix Uteri↗
PubMed1995

Intraepithelial neoplasia of the vulva.

Intraepithelial neoplasia of the vulva is being seen with increasing frequency. Awareness of this should prompt the clinician to carefully inspect the vulva on all patients. Reports strongly suggest a relationship between infection with human papillomavirus and vulvar intraepithelial neoplasia. The frequency with which this disease progresses to invasive carcinoma is unknown at present. However, it is obvious that it does occur. Both the warty and basaloid types of vulvar intraepithelial neoplasia are associated with HPV infection and are often associated with invasive squamous cell carcinoma of the vulva demonstrating similar morphologic characteristics. These changes are seen more often in younger women who smoke than in the older nonsmoking woman whose lesions do not appear to be HPV related. Both local excision and the carbon dioxide laser are effective for treating vulvar intraepithelial neoplasia. The choice of which approach to take depends upon the location and size of the lesion or lesions. Whichever approach is utilized, preservation of the normal vulvar anatomy and function are of paramount importance.

Carcinoma in Situ↗
PubMed1995

Colposcopically directed biopsy and loop excision of the transformation zone. Comparison of histologic findings.

We performed a retrospective comparison between the findings from colposcopically directed biopsies and those from loop excision of the transformation zone (LETZ) specimens. The correlation was satisfactory. When a low grade squamous intraepithelial lesion (SIL) was predicted on a cytologic smear and biopsy specimen, no cases of invasive carcinoma were found. In two (0.8%) cases in which a high grade SIL was predicted on the cervical smear and biopsy, microinvasive carcinoma was found in the LETZ specimen.

Adolescent↗
PubMed1994

Second primary cancer arising from the neovulva following reconstruction with myocutaneous flaps.

Myocutaneous flaps have been used for vulvar reconstruction following radical vulvectomy. For over 15 years the most common complications related to these flaps are sloughing of the skin and donor site wound infection. A new malignancy arising from the skin of the neovulva is an unusual occurrence. Two cases are presented. The skin of the neovulva may be exposed to the same neoplastic carcinogens that caused the initial lesion. In both patients, the polymerase chain reaction method failed to detect the presence of human papillomavirus DNA in either the initial lesion or the recurrent cancer.

Aged↗
PubMed1993

Continuous five-year treatment of patients with frequently recurring genital herpes simplex virus infection with acyclovir.

This study presents data relative to the efficacy and safety following the continuous use of oral acyclovir in the treatment of genital herpes over a 5-year period. In this study, 1,146 patients (53% males; 47% females) were originally enrolled. These included patients with a history of frequently recurring genital herpes (mean > 12 episodes per year). During the first year, patients were randomized between those receiving 400 mg of acyclovir twice daily and an equal number receiving placebo. Additionally, acyclovir was utilized for episodic treatment (ES) in both groups. Thereafter, patients received open-label acyclovir suppressive therapy for the remainder of the study period. Complete data are available on 389 patients who completed the fifth year of therapy. All the participants who completed the fifty year of the study had completed either 4 or 5 years of daily suppressive acyclovir therapy. During the first year, a significant decrease in the frequency of recurrences in patients receiving continuous acyclovir (SS) was noted as compared to the placebo group (1.7 vs. 12.5 recurrences; P < 0.0001). From year one to the end of year three, a progressive decrease in the frequency of recurrences was noted in both groups. Yet, those patients who had received SS for the full 3 years had significantly fewer recurrences than those who had received ES in the first year (P = 0.05). During years four and five, the decrease in frequency of recurrences between the ES and SS groups was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗
PubMed1992

Vulvar vestibulitis: significant clinical variables and treatment outcome.

The subject of vulvar vestibulitis was reviewed in regard to clinical variables that may be associated with this problem as well as the success of available treatment modalities. Questionnaires were returned by 71 patients diagnosed as having vulvar vestibulitis. Identical information was obtained from a comparison group of individuals with no clinical or physical findings suggesting this diagnosis. A history of recurrent candidiasis and previous condyloma acuminatum were the only variables noted more frequently in patients with vestibulitis. Among the patients treated by perineoplasty, 66% reported complete or significant alleviation of vulvar pain; 78% of the women noted a significant decrease in dyspareunia. Of the patients treated with intralesional interferon, six (50%) reported significant improvement in dyspareunia. Vulvar vestibulitis is a puzzling clinical entity whose etiology is not well understood. Perineoplasty still appears to be the treatment of choice in properly selected individuals.

Adolescent↗
PubMed1992

Advanced squamous cell carcinoma of the vulva after treatment for verrucous carcinoma. A case report.

Verrucous carcinoma of the vulva, a rare variant of squamous cell carcinoma, is a locally destructive, nonmetastasizing tumor. While controversy surrounds the choice of treatment for this lesion, which frequently recurs, it is generally accepted that a recurrence is almost always local, with histologic characteristics and biologic behavior the same as those of the primary tumor. A case of squamous cell carcinoma of the vulva with involvement of the regional lymph nodes after treatment of verrucous carcinoma is reported to increase awareness of the potential biologic behavior of this uncommon tumor.

Carcinoma, Papillary↗
PubMed1992

Herpes genitalis.

In conclusion, herpes genitalis has become one of the most common sexually transmitted diseases and has reached epidemic proportions. It presents a grave risk to immunocompromised patients and to newborns. The advent of effective therapy with acyclovir has dramatically modified the morbidity and mortality of disseminated herpesvirus infection and has helped in the therapy of primary and recurrent herpes genitalis. Current work has indicated that the disease can be transmitted by asymptomatic patients who are shedding the virus in the absence of visible lesions, which presents a diagnostic and therapeutic problem, especially significant for the pregnant patient, because infection of the neonate leads to serious consequences. Close follow-up of the pregnant woman with genital herpes therefore is imperative to minimize the risk to the newborn. At this time, no vaccines have been demonstrated to be safe and effective; therefore, prevention is of the utmost importance.

Diagnosis, Differential↗
PubMed1991

Cervical carcinoma metastatic to the skull, heart, and lungs: analysis for human papillomavirus DNA.

In this case report we present a 21-year-old patient with stage IV cervical carcinoma metastatic to the skull at the time of diagnosis. The patient had two previous negative Pap smears performed 10 months and 15 months prior to the time of diagnosis. Postmortem examination 2 months following diagnosis showed cardiac and pulmonary metastases. Human papillomavirus (HPV) DNA was detected in the primary cervical tumor and skull metastasis, but absent in the cardiac and pulmonary metastases. This study details the first report in the medical literature of a skull metastasis present at the time of diagnosis of cervical carcinoma. It also represents the first report of HPV-negative metastases arising from an HPV-positive cervical cancer.

Adult↗
PubMed1991

Increased risk of profound weight loss among women exposed to diethylstilbestrol in utero.

We surveyed 1711 women exposed to diethylstilbestrol in utero, and 919 women not exposed, concerning lifetime weight loss histories. The prevalence of a history of unexplained profoundly low body weight (weight less than or equal to 80% of expected weight for age, sex, and height) was 18.7 per 1000 in the exposed group compared to 3.3 per 1000 in the unexposed group; a 5.72 to 1 ratio of increased risk.

Adult↗