The new era of automated immunoassay

Use of immunoassays and other ligand-binding assays in clinical diagnosis has increased dramatically during the last several years. Despite impressive technical advances, "mass production" of these assays in a routine laboratory still presents many difficulties. This review of ligand-binding assay technology highlights some recent developments, emphasizing challenges and possible solutions for cost-effective patient care.     

Human papillomavirus type 16 in vulvar carcinoma, vulvar intraepithelial neoplasia, and associated cervical neoplasia.

Vulvar intraepithelial neoplasia (VIN) is becoming more widespread and the patients are becoming still younger. Although progression to invasive vulvar carcinoma is uncommon, local recurrences are frequent and about one-quarter of the patients have multicentric genital disease. The aim of the present study was to search for a possible significant association of human papillomavirus (HPV) infection with vulvar carcinoma, recurrences, and multicentric disease. We used the polymerase chain reaction to examine vulvar and cervical biopsies from 43 patients with vulvar neoplasia for HPV type 16, which is the subtype most often detected in genital malignant or premalignant lesions. HPV 16 DNA sequences were found in 14 of 24 (58%) vulvar squamous carcinomas and in 15 of 19 (79%) VIN lesions. Nine patients (21%) had associated cervical neoplasia and six of these harbored HPV 16 in both lesions. Patients with recurrent intraepithelial neoplasia had a significantly higher incidence of HPV 16-positive lesions. No association was found with regard to the occurrence of multicentric disease or risk of malignant progression.     

Glucuronidation of carcinogenic arylamines and their N-hydroxy derivatives by rat and human phenol UDP-glucuronosyltransferases of the UGT1 gene complex

Since carcinogenic arylamines are sequentially oxidized andconjugated with glucuronic acid, differences in glucuronidationmay critically determine the toxic potential of these compounds.Therefore, N-glucuronldation of 1- and 2-naphthylamine (1-NAand 2-NA), 4-aminobiphenyl (4-ABP) and their N-hydroxy derivativeswas investigated using rat and human liver microsomes and V79cell-expressed phenol UDP-glucuronosyltransferases (UGT) ofthe UGTl gene complex. Cell-expressed UGTs included rat andhuman UGT 1.6, which are known to conjugate planar phenols,and human UGT1.7, conjugating both planar and bulky phenols,(i) N-Glucuronidation of 1- and 2-NA and of N-hydroxy-2-NA wasinducible by 3-methylcholanthrene in rat liver microsomes whereasN-glucuronidation of the bulky arylamines 4-ABP and N-hydroxy-4-ABPwas not In support of these findings mutagenicity of N-hydroxy-2-NAin the Ames test was markedly reduced upon addition of UDP-glucuronicacid using liver homogenates from 3-methylcholanthrene-treatedrats, (ii) With cell-expressed rat UGT1.6, non-carcinogenic1-NA was conjugated with the highest rate and with higher affinitythan 2-NA. UGT1.6 showed poor activity towards N-hydroxy-4-ABPand 4-ABP. (iii) Substrate specificity of human UGT1.6 alsoappeared to be limited to planar 1-NA, 2-NA and its N-hydroxyderivative, whereas UGT1.7 showed broader substrate specificity,including the bulky arylamine 4-ABP and its /V-hydroxy derivative.The results suggest marked differences in substrate specificityof different UGT isozymes for arylamines and their N-hydroxyderivatives.     

Sexual function and somatopsychic reactions after local excision of vulvar intra-epithelial neoplasia.

Eighteen patients, under the age of 60 years, who have been treated with local excision of the vulva, participated in the study in which sexual function and somatopsychic reactions were evaluated by personal interviews. Furthermore both objective and subjective cosmetic results were registered. After this type of operation, fewer than one-third of the patients had postoperative sexual and somatopsychic problems, whereas more than half of the patients undergoing vulvectomy did report such problems. Fourteen out of 18 patients were satisfied with the cosmetic result and in 12 of the patients no disfiguration was found. This study shows that local excision of intra-epithelial neoplasia of the vulva is far less sexually traumatic than is vulvectomy.     

Dermatofibrosarcoma protuberans of the vulva

A woman aged 52 years had a tumor of the mons pubis. The morphologic picture, featuring a whirling of spindle cells with long slender, interdigitating cell processes and so-called labyrinth nuclei, conformed to a dermatofibrosarcoma protuberans. Wide local excision is sufficient therapy, but more experience with this rare sarcoma of the vulva is necessary.     

Sexual function and somatopsychic reactions in vulvectomy-operated women and their partners

Sexual function and somatopsychic reactions were examined in 25 women following vulvectomy and in 15 of their partners. More than half of the women had both sexual dysfunction and psychological problems. Their partners had no sexual dysfunction but almost half had psychological problems. An important reason for this seems to be insufficient information and advice both pre- and postoperatively and failure to recognize a developing stricture of the introitus vaginae. Frequent control and advice to both partners both pre- and postoperatively is desirable. Less extensive surgical procedures in selected cases should be considered.