Biomedical subjects

T C Wright

Publications and source records attributed to T C Wright.

At least 73 records · Page 4Linked to original sources

PubMed1995

Human papillomavirus infection in human immunodeficiency virus-seropositive women.

OBJECTIVE: To compare the prevalence of human papillomavirus (HPV) infections in women who are seropositive and seronegative for human immunodeficiency virus (HIV), and to determine if associations between HPV and cervical disease are altered in HIV-seropositive women. METHODS: In this cross-sectional study, 344 HIV-seropositive and 325 HIV-seronegative women underwent colposcopy and HPV DNA testing. RESULTS: Human immunodeficiency virus-seropositive women were more likely than HIV-seronegative women to have HPV DNA of any type detected (60 versus 36%, P < .001). Infections with HPV type 16 (27 versus 17%, P < .05), type 18 (24 versus 9%, P < .05), and more than one type of HPV (51 versus 26%, P < .05) were also more common in HIV-positive women. Although both latent HPV infection and HPV infections associated with cervical intraepithelial neoplasia (CIN) were more prevalent in the HIV-seropositive group, the ratio between these two types of infections was altered markedly in the HIV-seropositive women. Human immunodeficiency virus-seropositive women who were HPV-infected were significantly more likely to have CIN than were HPV-infected HIV-seronegative women, an increase observed at all levels of immunosuppression. Analysis of specific HPV types associated with latent HPV infection and CIN indicated that HIV seropositivity only minimally alters the known associations between specific types of HPV and cervical disease. CONCLUSION: Human papillomavirus infections are more common among HIV-seropositive women at all levels of immunosuppression. However, relationships between HIV and HPV are complex and cannot be explained completely by an increased susceptibility to new HPV infections in the immunosuppressed patient.

Adult↗

PubMed1995

Treating vaginal and external anogenital condylomas with electrosurgery vs CO2 laser ablation.

Our objective was to assess the technical characteristics, side effects, complications, and effectiveness of electrosurgery vs continuous wave CO2 laser in the treatment of genital warts. This open clinical trial was made up of 208 evaluable patients (135 women and 73 men) with vaginal and external anogenital condylomas. To avoid selection bias, in each patient half of the lesions measuring 2 cm2 or greater total linear area were treated with loop electroexcision and ball electrofulguration, and the other half were treated with CO2 laser excision and vaporization in a continuous wave mode spot welding. All patients were followed for at least 6 months (maximum 18 months, mean 8 months) after the last treatment received. The average operative time was 6 min for electrosurgery and 8 min for laser. Healing was completed in 95% of patients with a lesional area of 5 cm2 or less and 100% of patients with 5 cm2 or larger by the third and sixth postoperative week, respectively. Severe discomfort occurred in 12% of patients, and 4% of patients developed delayed complications, including vitiligo and scarring, irrespective of treatment modalities used. Complete clearance of warts in women and men after a single (51% and 38%) and multiple (75% and 64%) treatments were similar in areas treated with electrosurgery and CO2 laser. Electrosurgery appears to be as effective as continuous wave CO2 laser for treating vaginal and external anogenital condylomas, particularly those limited to a 5 cm2 or less area.

Adult↗

PubMed1995

Loop excision of the uterine cervix.

Over the past three years, loop excision has become a standard form of therapy for cervical intraepithelial neoplasia. Clinical trials have found loop excision to be faster and easier than laser ablation for treating cervical intraepithelial neoplasia and to have similar complication and success rates. In addition, loop excision produces a specimen that is suitable for histopathologic evaluation in the majority of patients. As our clinical experience with loop excision has increased, little impact on fertility and pregnancy outcome has been found, but there continues to be concern about overuse of the technique as a method of evaluating women with low-grade abnormal Papanicolaou smears.

Cervix Uteri↗

PubMed1994

Cervical intraepithelial neoplasia in women infected with the human immunodeficiency virus: outcome after loop electrosurgical excision.

Our clinical experience with loop electrosurgical excision as therapy for cervical intraepithelial neoplasia (CIN) in women infected with human immunodeficiency virus is described. Information for this analysis was obtained from a retrospective chart review of all women with biopsy-confirmed CIN treated by loop electrosurgical excision who attended our colposcopy clinic during January 1991 to September 1992. Outcomes in women known to be HIV-seropositive were compared to those in women of unknown HIV serostatus. Patients included in the analysis were followed for at least 6 months or until the documentation of recurrent/persistent CIN, and all had at least one post-treatment colposcopic examination, including endocervical curettage and cervical biopsy of any acetowhite lesions. Recurrent/persistent CIN following loop excision was documented in 56% (19 of 34) HIV-infected women compared with 13% (10 of 80) women of unknown serostatus (OR 8.9, P < 0.001). HIV-infected women had a significantly higher rate of recurrent/persistent CIN than women of unknown serostatus, regardless of grade of CIN. In HIV-infected women, recurrent/persistent CIN following loop excision developed in 20% (1 of 5) with CD4+ T-lymphocyte counts > 500 cells/microliters compared to 61% (11 of 18) with CD4+ counts < or = 500 cells/microliters (P = 0.13). Loop electrosurgical excision has a high failure rate in HIV-infected women, and this failure rate may increase as the level of immunosuppression increases.

Adult↗

PubMed1994

Cervical intraepithelial neoplasia in women infected with human immunodeficiency virus: prevalence, risk factors, and validity of Papanicolaou smears. New York Cervical Disease Study.

OBJECTIVE: To define the prevalence of cervical intraepithelial neoplasia (CIN), the validity of Papanicolaou tests, and the associations between CIN and risk factors for cervical disease in human immunodeficiency virus (HIV)-infected women. METHODS: In this cross-sectional study, we enrolled 398 HIV-seropositive and 357 HIV-seronegative women from two HIV-AIDS clinics, two sexually transmitted disease clinics, a methadone clinic, and a clinic for participants in an HIV heterosexual transmission study. Each woman was interviewed and underwent a cytologic and colposcopic evaluation, and was tested for human papillomavirus (HPV) DNA. RESULTS: Eighty (20%) of the 398 HIV-seropositive women compared to 15 (4%) of the 357 seronegative women had colposcopically confirmed CIN (odds ratio 5.7; P < .001). No invasive cancers were found. The sensitivity and specificity of Papanicolaou tests in seropositive women were 81 and 87%, respectively. By multiple logistic regression analysis using a model that included behavioral and biologic risk factors for CIN, CIN was independently associated with HPV infection (odds ratio 9.8), HIV infection (odds ratio 3.5), CD4+ T-lymphocyte count less than 200 cells/microL (odds ratio 2.7), and age greater than 34 years (odds ratio 2.0). CONCLUSIONS: Cervical intraepithelial neoplasia is a common finding in HIV-infected women. However, the results of this study suggest that Papanicolaou tests should be effective for detecting cervical disease in this population.

Adolescent↗

PubMed1994

Analysis of lower genital tract lesions clinically suspicious for condylomata using in situ hybridization and the polymerase chain reaction for the detection of human papillomavirus.

The presence of human papillomavirus was analyzed in 123 biopsy specimens of lower genital tract lesions, clinically considered to be condyloma, using both in situ hybridization and the polymerase chain reaction. Using standard histologic criteria only 22% of the lesions could be diagnosed as condyloma, 17% had features suggestive but not diagnostic of condyloma and 61% lacked the histologic features of condyloma. Human papillomavirus was detected by in situ hybridization in 89% of the lesions with the histologic features of condyloma but in only 3% of the biopsy specimens lacking the histologic features of condyloma. Fifty percent of lesions that had histologic features suggestive, but not diagnostic for, condyloma contained human papillomavirus by in situ hybridization. Using polymerase chain reaction similar results were found. This study underscores the usefulness of human papillomavirus detection methods for analyzing histologically equivocal lesions of the lower genital tract.

Condylomata Acuminata↗

PubMed1994

Expression of cellular retinol- and cellular retinoic acid-binding proteins in the rat cervical epithelium is regulated by endocrine stimuli during normal squamous metaplasia.

To determine the potential roles of retinoids in the growth and differentiation of the reproductive tract epithelium, we have studied the expression of the cellular retinol- and retinoic acid-binding proteins, CRBP I and CRABP I, in the reproductive tract of female rats. CRBP I and CRABP I gene expression have been examined in the oviduct, ovary, uterus, and particularly in the cervix, which normally undergoes a cyclical squamous metaplasia during the estrus cycle. CRBP I was expressed in all four tissues examined, whereas CRABP I was expressed predominantly in cervix and uterus. In the cervix, CRBP I was detected in all epithelial layers including the columnar epithelium but was greatly reduced in the superficial, cornified layers of the stratified squamous epithelium. CRABP I was localized to the basement membrane region of the epithelium with the strongest expression in the basal layer of epithelial cells. While the expression of CRBP I and CRABP I in the keratinizing exocervix changed during the estrus cycle, it remained constant in the incompletely keratinized endocervix. The highest levels of CRBP I were seen during anestrus and proestrus, and for CRABP I during proestrus. Both CRBP I and CRABP I levels fell to barely detectable levels during estrus and metestrus. Using estrogen repletion of ovariectomized rats, we found that CRABP I levels transiently increased during the early proliferative response to estrogen, whereas CRBP I levels gradually declined, becoming barely detectable by 24 to 48 hours. These results suggest that CRBP I and CRABP I play different roles in the cyclical squamous metaplasia normally occurring in this tissue and that hormonal control of CRBP I and CRABP I expression might modulate the retinoid responsiveness of the epithelium during this process.

Animals↗

PubMed1993

Controversies in the management of low-grade cervical intraepithelial neoplasia.

During the last 30 years, there have been major changes in the methods used to diagnose and manage cervical cancer precursors. Early detection of precursors through mass cytologic screening programs and the eradication of these precursors when detected are currently the cornerstone of policies aimed at reducing cervical cancer. These policies have been successful, resulting in a marked reduction in both the number of cases and deaths from cervical cancer in North America and Western Europe. Recently, however, significant controversy has arisen over several aspects of the diagnosis and management of cervical intraepithelial neoplasia (CIN). Two of the most important of these controversies are whether all patients with low-grade CIN lesions require therapy and what is the appropriate role for the newly introduced loop electrosurgical excision procedure in managing patients with CIN. In this article, these controversies are reviewed with emphasis placed on how these controversies affect the practicing gynecologist.

Carcinoma in Situ↗

PubMed1993

Relationships between c-Ki-ras mutations, HPV types, and prognostic indicators in invasive endocervical adenocarcinomas.

OBJECTIVE: Ras gene mutations have been identified in squamous cell carcinomas of the cervix and are associated with advanced-stage tumors. The current study was designed to determine the prevalence of c-Ki-ras mutations in invasive endocervical adenocarcinomas and associations between mutations, HPV status, and known prognostic indicators. METHODS: Paraffin-embedded tissue samples from 32 cases of invasive adenocarcinoma of the endocervix were analyzed for the presence of c-Ki-ras mutations by amplification of DNA extracted from paraffin blocks using the polymerase chain reaction (PCR) and subsequent restriction enzyme digestion of the amplimers. This method allows detection of aspartic acid mutations of the c-Ki-ras gene at codons 12 and 13. Samples were also analyzed for the presence of HPV DNA using PCR and either "consensus sequence" primers or "type-specific" primers for HPVs 16 and 18. Patients' charts were reviewed for clinical information and correlations between clinical outcome and known prognostic indicators and the presence of c-Ki-ras mutations was assessed. RESULTS: c-Ki-ras codon 12 mutations were detected in only 4 of the 32 cases (12.5%) of invasive endocervical adenocarcinomas examined. No codon 13 mutations were detected. Fifty-nine percent of the cases were HPV 16 or HPV 18 DNA positive and only 1 of the 4 cases with a codon 12 mutation was associated with HPV 16 or HPV 18. There were no significant associations between stage or grade of tumor or outcome and the presence of codon 12 mutations. However, using the observed survival as computed by the Berkson Gage Method at 12 months, the estimated median survival for patients with c-Ki-ras codon 12 mutations is 29 months compared to 68 months for patients lacking codon 12 mutations. CONCLUSIONS: These results indicate that c-Ki-ras codons 12 and 13 mutations are uncommon in invasive endocervical adenocarcinomas.

Adenocarcinoma↗

PubMed1993

Outpatient surgery in gynecologic oncology.

There has been an enormous change in outpatient-directed surgery for human papillomavirus-related lesions of the anogenital tract over the past 2 years. Concern that a small number of invasive cancers were being missed during evaluation and were being treated as precursors led many investigators to suggest excisional rather than ablative procedures for precursor management. The use of cold-knife or carbon dioxide laser excisions was recommend as the procedure of choice--particularly for high-grade cervical intraepithelial neoplasia lesions. With the introduction of the loop electrosurgical excision procedure, the focus rapidly shifted to electrosurgical excision, which has been found to be clinically useful, although with caveats, and is now the procedure of choice.

Ambulatory Surgical Procedures↗

PubMed1992

Relationship of human papillomavirus type to grade of cervical intraepithelial neoplasia.

OBJECTIVE--To determine the relationship of human papillomavirus (HPV) type to grade of cervical intraepithelial neoplasia (CIN) in a large series of cases. DESIGN--A survey of HPV types in CIN lesions detected using a new, highly accurate method for typing HPV that is based on restriction fragment length polymorphism analysis of amplimers produced during polymerase chain amplification of the conserved L1 region of HPV using consensus primers. SETTING--Private gynecologists' offices and inner-city colposcopy clinics. PATIENTS--A convenience sample of 276 HPV DNA-positive cervical biopsy specimens or samples from patients undergoing colposcopy for abnormal Papanicolaou smears. INTERVENTION--None. MAIN OUTCOME MEASURE(S)--Human papillomavirus type(s). RESULTS--Cervical intraepithelial neoplasia 1 lesions were relatively heterogeneous with regard to associated HPV types. Nineteen percent of CIN 1 lesions were associated with HPV types 6 or 11; 29% contained HPV types 16, 18, or 33; and 19% were associated with "novel types" of HPV. It was also found that 22% of CIN 1 lesions were associated with more than one HPV type. In contrast to CIN 1, both CIN 2 and CIN 3 were relatively homogeneous with regard to associated HPV types. Eighty-eight percent of CIN 2 and 3 lesions contained HPV types 16, 18, or 33. Unlike CIN 1 lesions, which often contained multiple types of HPV, only 7% of CIN 2 and 3 lesions were associated with multiple HPV types. CONCLUSIONS--Cervical intraepithelial neoplasia should be classified into two separate categories--low-grade and high-grade CIN. Since only 29% of low-grade lesions are associated with HPV types 16, 18, or 33, HPV type could potentially play a role in determining the most appropriate clinical management of patients with low-grade CIN. However, prospective follow-up studies of lesional behavior based on HPV type are required before clinical recommendations can be made.

DNA, Viral↗

PubMed1992

Heparin inhibits the attachment and growth of Balb/c-3T3 fibroblasts on collagen substrata.

In investigating the role of cell-extracellular matrix interactions in cell adhesion and growth control, the effects of heparin on cell-collagen interactions were examined. Exponentially growing Balb/c-3T3 fibroblasts were radiolabelled with 3H-thymidine and detached from tissue culture surfaces using EDTA, and cell attachment to various types of collagen substrata was assayed in the presence or absence of heparin or other glycosaminoglycans (GAGs) or dextran sulfate (40 K). Cells attached readily (70-90%) to films of types I and V, but not to type III collagen. The number of cells bound to types I and V collagen films was inhibited by 10-50% when heparin was present from 0.1-100 micrograms/ml. Cell-collagen attachment was also inhibited by dextran sulfate, and to a lesser extent by dermatan sulfate, but chondroitin sulfates A and C and hyaluronic acid showed no effect. Heparin was active even at early time points in the adhesion assay, suggesting it may disrupt cell-collagen attachment. To study the effects of heparin in modulating cell growth on collagen, growth arrested cells cultured on type I collagen films were serum stimulated in the presence of heparin or other GAGs for 3 days. Growth was inhibited (greater than 40%) only by heparin and dextran sulfate. Interaction of heparin fragments (Mr less than or equal to 6KD) with type I collagen was analyzed by affinity co-electrophoresis (Lee and Lander, 1991) and showed higher affinity heparin binding to native as compared with denatured collagen. These data suggest that sites within native collagen may mediate Balb cell-collagen and heparin-collagen interactions, and such interactions may be relevant towards understanding heparin's antiproliferative activity in vivo and in vitro.

3T3 Cells↗

PubMed1992

Typing of human papillomaviruses by polymerase chain reaction amplification with L1 consensus primers and RFLP analysis.

Human papillomaviruses (HPV) cause benign and malignant lesions of the epithelial and mucosal surfaces. Certain virus types are associated with cervical carcinomas, while others are associated with benign condylomata. We have developed a rapid method for determining HPV type that is based on restriction fragment length polymorphism (RFLP) analysis within the L1 region of HPVs that is amplified by PCR using the consensus primers described by Manos et al. Analysis of the product generated by PCR amplification of plasmids containing cloned HPV genomes and of 88 clinical specimens, known to contain HPV viral DNA by previous hybridization analysis, revealed that this method is useful for typing HPV sequences amplified from a variety of sources including cervical lavages, fresh tissue, and paraffin-embedded formalin-fixed biopsy material. The method can differentiate between most known types of HPV and discriminate between infections with single, multiple or novel HPV types. A high correlation (86%) was obtained when this method was compared with PCR amplification and Southern blot hybridization analysis of PCR product, or Southern blot hybridization analysis of total genomic DNA. Differences in typing occurred mostly for specimens that contained multiple or new/unknown HPV types. However, RFLP typing easily identified repeated patterns for new HPV types that were not detected by the other methods. In summary, PCR-RFLP typing is a sensitive and specific method to identify and characterize rapidly HPV DNA in clinical specimens from a variety of sources.

Blotting, Southern↗

PubMed1992

Human papillomavirus.

In the past year, new data have been published on the molecular biology of human papillomavirus infections and their relationship to cervical neoplasia. As molecular techniques have become more sophisticated and as the molecular knowledge of human papilloma-virus infections has been pursued in greater depth, it is increasingly apparent that this human tumor DNA virus is similar to a number of other oncogenic DNA viruses that have been described and well studied. These viruses appear to act through a common pathway of producing oncogenic proteins that interfere with key signalling elements that normally control the process of cell division. With a better mechanistic knowledge, it should be possible to design new therapeutic approaches to treating human papillomavirus-associated disease that are directed toward specific cellular events such as turning off the production of E6 and E7 proteins or restoring the activity of pRB or p53. Increased attention has also been turned to immunologic aspects of HPV infections, and a number of groups are eagerly pursuing the possibility of using simple office-based procedures to detect specific proteins encoded for by the human papillomavirus open reading frames in an attempt to determine who has been infected, is actively infected, and has proteins being produced that are indicative of neoplasia. From the clinical point of view, the use of outpatient excisional techniques such as the loop electrosurgical excision procedure is rapidly supplanting ablative techniques because of their superior ability to identify early invasive carcinomas and adenocarcinomas in situ that have not been detected by colposcopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Localization of cellular retinoid-binding proteins in human cervical intraepithelial neoplasia and invasive carcinoma.

Cellular retinoic acid-binding protein (CRABP) and cellular retinol-binding protein (CRBP) were localized in biopsies of normal squamous epithelium, cervical intraepithelial neoplasia (CIN), and invasive squamous cell cancer of the cervix uteri by immunohistochemistry. In both the normal stratified squamous epithelium of the exocervix and low-grade CIN, CRABP I was present predominantly in the basal layer of the epithelium. The more superficial, differentiated cell layers lacked immunoreactive protein. In high-grade CIN (CIN2-3), the distribution of CRABP I was altered. Immunoreactive CRABP I was detected in all layers of high-grade CIN. In squamous cell carcinoma of the cervix, CRABP I was detected in cells throughout the tumor but was minimal in cells demonstrating squamous differentiation. In contrast to CRABP I, CRBP was diffusely present throughout the cervical epithelium irrespective of the state of differentiation or the presence of disease.

Adolescent↗

PubMed1992

Loop electrosurgical excision procedure for CIN.

The loop electrosurgical excision procedure, also referred to as large loop excision of the transformation zone, is gaining acceptance in the United States as a method for treating cervical intraepithelial neoplasia. Loop excision of cervical tissue is accomplished using a high-frequency alternating current (radiofrequency) and thin wire loop electrodes. Loop excision may be in the form of simple excision of the transformation zone or electrosurgical loop conization. The specimens obtained using this technique are suitable for histologic evaluation. Loop excision, which is usually performed under local anesthesia, is associated with minimal short-term and long-term morbidity. Patient acceptance is high. Family physicians who perform colposcopy should consider using loop electrosurgical excision to treat cervical intraepithelial neoplasia in the outpatient setting.

Ambulatory Surgical Procedures↗

PubMed1992

Comparison of specimens removed by CO2 laser conization and the loop electrosurgical excision procedure.

A comparison is made of the histologic changes in the cervical epithelium and stroma following CO2 laser conization and office excisional biopsy of cervical tissue using the loop electrosurgical excision procedure. In both types of specimens, two zones of thermal injury were detected. The zone at the margin of resection measured approximately 50 microns in thickness and was characterized by extensive carbonization and charring. The other zone was much more variable in thickness and characterized by tissue coagulation, but lacked charring. No significant difference in the biocharacteristics or extent of thermal damage was detected between the methods. For 11 specimens obtained with the CO2 laser, the coagulated zone ranged from 130-750 microns in greatest thickness; the mean thickness was 411 microns. For 40 specimens obtained using the loop procedure, the range of thickness of the coagulated zone was 150-830 microns, and the mean thickness was 396 microns. The difference in the mean value of thermal injury (measured in microns) between the laser and loop procedures was not significant (Student t test; P = .79). Extensive areas of carbonization and epithelial distortion at the margins of excision were only occasionally present in specimens obtained by the electrosurgical excision procedure but almost invariably present in CO2 laser specimens. However, in all cases it was possible to evaluate the epithelium and the stroma both histologically and cytologically.

Carbon Dioxide↗

PubMed1992

Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure.

In selected patients with cervical intraepithelial neoplasia (CIN), outpatient ablative procedures represent a readily accepted and highly effective treatment modality. The recently introduced loop electrosurgical excision procedure offers a quick and simple alternative to cryotherapy and laser ablation for treating CIN, and has the distinct advantage of allowing both diagnosis and treatment of selected patients at a single visit. This report presents our clinical experience treating 432 patients with CIN using the loop electrosurgical excision procedure on an outpatient basis. Small loop electrodes were used to excise CIN lesions in 275 patients, and large loop electrodes were used in 157. When performed on an outpatient basis under local anesthesia, loop excision was well tolerated by patients with only minimal discomfort. Post-treatment bleeding occurred in less than 2% of the subjects and responded to either recauterization or packing of the cervix. Post-treatment stenosis occurred in less than 1%. The success rate of the loop electrosurgical excision procedure, as defined by absence of cytologic, histologic, or colposcopic lesions 4-48 months after therapy, was 80% for women treated using the small loop electrodes. Ninety percent of all patients treated using the large loop electrodes were free of disease during 6-12 months of follow-up. For women being treated for primary (as opposed to recurrent) disease, the success rate with large loop electrodes was 94%.

Carcinoma in Situ↗