PubMed HealthSearch

Biomedical subjects

W Lancaster

Publications and source records attributed to W Lancaster.

At least 19 recordsLinked to original sources

The HPV 6 E6/E7 transforming genes are expressed in inverted papilloma.

A role for human papilloma virus (HPV) infection in the pathogenesis of head and neck neoplasms has gained support in recent years. Expression of two early-region HPV genes, E6 and E7, is widely accepted as essential for viral-induced carcinomas of the genital tract. These oncoproteins interact with the products of the cellular tumor suppressor genes, p53 and retinoblastoma, and inactivate them. Examining E6/E7 transforming gene expression is an important step toward elucidating the pathogenesis of HPV in head and neck neoplasms. We introduce nasal inverted papilloma (IP) as a novel system for evaluating viral genomic expression and transforming gene regulation of tumorigenesis by virtue of its association to HPV infection and potential for malignant progression. We describe here a reverse transcriptase-polymerase chain reaction approach for the detection of HPV E6/E7-specific transcripts in RNA extracted from IR. A primer pair flanking previously mapped HPV 6 E6/E7 splice donor/acceptor sites was used to direct amplification of cDNA. Reverse transcriptase-polymerase chain reaction experiments generated products representing the 1.2 Kb E1E4 splice transcript and a smaller unclassified fragment in IP from two patients. These results provide evidence for HPV 6 E6/E7 expression in IP with the potential to encode transforming proteins.

DNA, Viral

Reform of primary health care: effective use of advanced practice nurses.

Never before has American society undergone such dramatic and pervasive changes as those currently effecting national health care needs. New strategies to meet the health care needs created by societal changes must be identified. Consumers, employers, providers, and third-party payers are calling for more cost effective health care, better access and better quality. Simultaneously, the United States has a shortage of primary care physicians. While many people claim that one strategy necessary for health care reform is to change the primary care physician/specialty mix of providers, there are some inherent fallacies in this argument. Training for primary care medicine has historically been available; however, the majority of physicians choose specialty practice. The financial rewards are much better in specialty practice than in primary care. If the U.S. were to alter the reward structure and make primary care more attractive to physicians, the objective of controlling costs could not be met. However, there is another alternative and that is to change the provider mix. Since advanced practice nurses (APNs) have a long and successful history of taking care of primary care patients, why not make them the point of first contact? APNs working collaboratively with physicians could more cost effectively manage care for large numbers of ambulatory patients than are being adequately handled at present. APNs, defined as nurse practitioners, certified nurse midwives and clinical nurse specialists, provide high quality, cost effective, and comprehensive primary care services. Increased use of APNs in disease prevention, illness management, and health education is one way of meeting health care needs of Americans. Innovative strategies for more effectively using APNs must also be identified and implemented. Also, artificial and politically imposed barriers to effective utilization of APNs must be removed.

Evaluation Studies as Topic

The genetic drift of human papillomavirus type 16 is a means of reconstructing prehistoric viral spread and the movement of ancient human populations.

We have investigated the diversity of a hypervariable segment of the human papillomavirus type 16 (HPV-16) genome among 301 virus isolates that were collected from 25 different ethnic groups and geographic locations. Altogether, we distinguished 48 different variants that had diversified from one another along five phylogenetic branches. Variants from two of these branches were nearly completely confined to Africa. Variants from a third branch were the only variants identified in Europeans but occurred at lower frequency in all other ethnic groups. A fourth branch was specific for Japanese and Chinese isolates. A small fraction of all isolates from Asia and from indigenous as well as immigrant populations in the Americas formed a fifth branch. Important patterns of HPV-16 phylogeny suggested coevolution of the virus with people of the three major human races, namely, Africans, Caucasians, and East Asians. But several minor patterns are indicative of smaller bottlenecks of viral evolution and spread, which may correlate with the migration of ethnic groups in prehistoric times. The colonization of the Americas by Europeans and Africans is reflected in the composition of their HPV-16 variants. We discuss arguments that today's HPV-16 genomes represent a degree of diversity that evolved over a large time span, probably exceeding 200,000 years, from a precursor genome that may have originated in Africa. The identification of molecular variants is a powerful epidemiological and phylogenetic tool for revealing the ancient spread of papillomaviruses, whose trace through the world has not yet been completely lost.

Africa

Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types.

During the years 1982-1989, 2627 women were recruited into eight studies analyzing the relationship between human papillomavirus (HPV) infection and cervical neoplasia. Subsequently, each individual was assigned as either a case or control, and each cervical sample was rescreened for HPV DNA by low-stringency Southern blot hybridization. Positive samples were retested at high stringency with specific probes for HPVs 6/11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 56, and (in most instances) 58. Most cases (153 cancers, 261 high-grade and 377 low-grade squamous intraepithelial lesions) had target or cone biopsies; all 270 borderline atypia subjects and more than 85% of the 1566 normal controls had cytology plus colposcopy/cytology. Scientists performing HPV testing were masked to the clinical diagnoses. Human papillomavirus DNA was detected in 79.3% of specimens from women with definite cervical disease (627 of 791), in 23.7% of borderline atypia subjects (64 of 270), and in 6.4% of normal subjects (101 of 1566). Graphic analysis of odds ratios at each point in the diagnostic spectrum defined four categories: 1) "low risk" (HPVs 6/11, 42, 43, and 44), present in 20.2% (76 of 377) of low-grade lesions but absent in all 153 cancers; 2) "intermediate risk" (HPVs 31, 33, 35, 51, 52, and 58), detected in 23.8% (62 of 261) of high-grade squamous intraepithelial lesions but only 10.5% (16 of 153) of cancers; 3) "high risk/HPV 16," associated with 47.1% of both high-grade intraepithelial lesions (123 of 261) and cancers (72 of 153); and 4) "high risk/HPV 18" (HPVs 18, 45, and 56), found in 26.8% (41 of 153) of invasive carcinomas but only 6.5% (17 of 261) of high-grade intraepithelial lesions. The presence of an oncogenic HPV type conferred relative risks ranging at 65.1-235.7 for the occurrence of a high-grade lesion and 31.1-296.1 for an invasive cancer.

Blotting, Southern

Tracking patient satisfaction at an academic medical center.

Rising consumer expectations for convenient, quality health care is forcing many hospitals to focus increasing attention to measuring consumer perception and satisfaction with the care provided. At the University of Virginia Health Sciences Center, getting in close touch with the consumer has assumed a strategic position. As one part of the evolving Marketing Information System, a patient satisfaction tracking system is being designed to illicit patient feedback and hospital responses to service issues, assess patient satisfaction with various services, serve as a benchmark for evaluating changes in satisfaction over time, and provide necessary information for medical center planning, marketing and evaluation.

Academic Medical Centers

A synthetic peptide defines a serologic IgA response to a human papillomavirus-encoded nuclear antigen expressed in virus-carrying cervical neoplasia.

The growing awareness of the role of human papillomavirus (HPV) in cervical carcinoma has triggered a search for uncomplicated detection methods. To define a serologic response to HPV, we synthesized peptides based on sequences deduced from the genome of HPV type 16, the most common malignancy-associated type of HPV. One of these peptides reacted with IgA antibodies present in sera from 24 of 33 patients with cervical intraepithelial neoplasia or cervical carcinoma, whereas this peptide reacted with only 6 of 27 sera from individuals without cervical intraepithelial neoplasia. Immunoaffinity-purified human antipeptide IgA antibodies detected HPV-specific 58- and 48-kDa proteins in cervical carcinoma cell extracts and also detected a nuclear antigen in HPV-carrying cervical cancer cell lines and cervical intraepithelial neoplasia biopsied tissue. These antigens were also detected with mouse monoclonal and rabbit polyclonal antibodies to the same peptide. The results indicate that screening for infection with malignancy-associated types of HPV may be possible by simple synthetic peptide-based serology.

Antibodies, Neoplasm

Statistical test of a short form of the speech-sounds perception test in a child population.

The adequacy of a shortened version of the children's Speech-Sounds Perception Test was examined. In two different groups of chronically ill children, stepwise multiple regression analysis demonstrated that the first three subtests (first 30 items) accounted for over 87% of the variance in the total 60-item test. The 30-item version appears to be as useful with children as the full 60-item test.

Adolescent

Neuropsychological sequelae of postradiation somnolence syndrome.

Postirradiation somnolence syndrome in children with acute lymphocytic leukemia treated with cranial irradiation has been identified as a possible precursor of later cognitive dysfunction. To test this, the neuropsychological evaluation of 48 children who developed somnolence syndrome was compared with that of 31 children who did not have the syndrome at approximately 1 1/2 and 3 3/4 years after treatment. No differences in performance between the two groups were found on many measures of neuropsychological functioning with the exception of fine motor speed. Children without somnolence syndrome scored somewhat less than normal on measures of academic achievement. No other differences from normal performance were noted in either group. The results of the study indicated that if children with somnolence are at greater risk for the development of cognitive dysfunction than those not manifesting the syndrome, such risks occur at a time farther from treatment than 3 to 4 years.

Adolescent

Language-related skills in children with acute lymphocytic leukemia.

The success of cranial irradiation and chemotherapy in the treatment of acute lymphocytic leukemia (ALL) has raised concerns about possible central nervous system damage in long-term survivors. The current study focused on language-related skill measures obtained as part of a neuropsychological test battery. Performance was analyzed as a function of age at diagnosis and age at evaluation in a sample of 110 children with ALL (mean age = 13.28 years). Results, although for the most part nonsignificant, do reveal significantly poorer performance on an Aphasia Screening Test rating by those diagnosed early (at or before five years of age) and assessed at or before 13 years of age when contrasted with those diagnosed early and assessed after their thirteenth year. Further analysis revealed a significant decline in spelling scores for those off therapy for more than two years. There was also a consistent trend for decline across most language-related skills measures as time off therapy increased. These results reflect either recovery from mild acute language dysfunction over time superimposed on a general trend for decline in language-related skills as time off therapy increases, or sampling error. Suggestions for future lines of investigation are discussed.

Achievement