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Human Papillomavirus and Cervical Cancer

Although the recent advances in cervical cancer diagnosis and treatment reduce the mortality of women with cervical cancer from the second leading cause of death to fifth place worldwide, still about 500,000 new cases are reported annually, and one-third of them are under the high risk of death (Sasagawa et al. 2005). Clinically, cervical cancer is an advanced stage of cervical intraepithelial lesions manifested from pre-invasive cervical intraepithelial neoplasia (CIN) due to the progressive infection of human papillomavirus (HPV) in keratinocytes of the uterine cervix (Walboomers et al. 1999). HPV belongs to a family of 120 double-stranded DNA viruses that have been linked to a number of epithelial cancers, and more often with the uterine cervix, where more than 90 of tumors contain HPV DNA (Tindle 2002). The abnormal uterine cervical clinical features as a result of HPV infection have a wide spectrum of diseases including warts (skin disease), low-grade dysplasia cervical...

Papillomaviruses in Human Cancers

Papillomas as benign tumors were the first proliferative condition for which the causation by a viral infection has been convincingly demonstrated. Tumor virology started with the cell-free transmission of oral dog warts by M'Fadyan and Hobday in 1898 (1). These experiments preceded the frequently cited studies of a cell-free transmission of a chicken sarcoma by Peyton Rous (2) by 13 yr and those by Ellermann and Bang (3) on a viral origin of chicken leukemias by 10 yr. Also prior to these observations, in 1907 Ciuffo in Italy (4) showed the transmissibility of human warts in self-inoculation experiments. Thus, papillomas emerged as the first (though benign) tumors with a proven viral etiology. The conversion of virus-caused papillomas into carcinomas was initially observed by Rous and Beard (5) and carefully analyzed by Rous and his associates in cottontail rabbits (6-8). In these years, Rous analyzed synergistic effects of this virus infection with chemical carcinogens and...

Natural History Of Hpv Infections

Infections with papillomaviruses require the availability of cells that are still capable to replicate (reviewed in 24). The outcome of an infectious event mainly depends on three factors (1) the multiplicity of infection, (2) the interaction with chemical or physical carcinogens, and (3) immunologic responsiveness. The role of the input multiplicity has been most carefully analyzed in cottontail rabbit papillomavirus (CRPV) infections (26-28). Infection of the rabbit skin with high doses of CRPV results in the emergence of papillomatous changes already 4-6 wk after inoculation. Low concentrations, however, result in papillomas only under conditions of treatment of the rabbit skin with chemical carcinogens (7,8,26). Without such treatment viral DNA can be demonstrated in normal tissue by the polymerase chain reaction (PCR). It appears that under these condition only the E1 gene is expressed which is required for the maintenance of the episomal state of the persisting viral DNA....

Treatment Of Genital Warts

Like CIN 1, genital warts are low grade in histology, have low potential for progression to malignancy, and need not be treated to prevent development of cancer. They usually are associated with HPV-6 or -11. In contrast to cervical LSIL or HSIL, however, genital warts may be symptomatic and may lead to burning, itching, bleeding, and psychological discomfort for patients. Relief of these symptoms is an acceptable indication to treat genital warts, and the diagnosis and treatment of these lesions is well described in a recent American Medical Association position paper (93,94). Treatment of genital warts generally falls into two categories patient-applied or provider-applied. Among the therapies now available for patients to use at home are purified podophyllotoxin (Condylox ) and imiquimod (Aldara ). These treatments have different mechanisms of action. Podophyllotoxin works by inhibiting micro-tubule formation and cell division imiquimod is believed to work by stimulating local...

Emerging Approaches To Prevention And Treatment Of Hpv Infection

At this time, HPV infection cannot be prevented other than through sexual abstinence. There is no evidence to suggest that condoms effectively prevent HPV acquisition. This is because condoms probably do not completely cover all areas that may harbor HPV-associated lesions such as the base of the penis. However, efforts are now underway to prevent initial HPV infection through a vaccine-based approach, and it is assumed that induction of mucosal humoral immunity is the necessary protective effect. Most work on a prophylactic vaccine to date has focused on the use of recombinant L1 protein as a vaccine candidate. The L1 protein is the major capsid protein of the HPV virion. When expressed in vitro, it autoassembles into a structure that closely resembles native HPV virions (99). These structures, termed virus-like particles (VLPs), have been shown to induce high titer neutralizing antibodies in animals (100-102) and in human Phase 1 trials (103) and to prevent lesion development in...

Human Papilloma Virus

Human papilloma virus (HPV) infections have two important clinical manifestations external genital warts (EGWs) and squamous intraepithelial lesions (30). A discussion of these neoplasms is beyond the scope of this chapter but screening and treatment issues can be found elsewhere (2). The majority of newly acquired HPV infections are asymptomatic. EGWs are diagnosed when visible warts occur in the genital area they can be discrete or coalesce into confluent plaques (30). The acetowhite test has not been definitely established as useful for diagnosis and has a low positive predictive value (30). Biopsy is seldom needed and is reserved for atypical lesions uncertain diagnosis progression of disease during treatment warts that appear pigmented, indurated, ulcerated, or fixed to underlying structures or warts that are 1 cm2. An entire examination of the genitalia is warranted because EGWs frequently occur on multiple genital sites. Speculum examination assessing for vaginal and cervical...

Natural History Of Cervical Hpv Infection And Csil

Cervix Cancer Lsil

For years there was debate about the modes of acquisition of anogenital HPV infection. There is now a consensus that the great majority of cervical HPV infections are acquired through sexual transmission (5,6). HPV is one of the most common sexually transmitted agents, and estimates are that about 75 of the general population aged 15-49 yr acquires at least one genital HPV type during their lifetimes (7). Epidemiologic studies of cervical HPV infection suggest that the age-related prevalence of HPV infection, as determined by polymerase chain reaction (PCR), is highest among women in their late teens and early 20s (8). These data suggest that that most women acquire HPV infection relatively early after initiation of sexual activity. The age-related prevalence of cervical HPV infection declines thereafter, probably through development of immunity to HPV. HPV infection in these women has either been cleared or the level of infection may have been reduced to levels that are undetectable...

Risk Factors For Anogenital Sil And Cancer Other Than Hpv Infection

Clearly HPV infection is one of the most important risk factors for anogenital SIL and cancer, and HPV infection is likely to be necessary for development of almost all of these lesions. Sexual risk factors such as number of sexual partners, age at first intercourse, and parity have long been associated with cervical cancer, but these likely reflect risk for acquisition of HPV infection. However, although the age-related prevalence of cervical LSIL parallels that of infection, only a small proportion of women who acquire HPV infection develop clinically detectable LSIL. An even smaller proportion of these women develop HSIL or invasive cervical cancer. This reflects the current understanding that HPV infection may be necessary but insufficient for development of CSIL and cervical cancer. The paradigm is that HPV infection contributes to carcinogenesis indirectly by stimulating cellular proliferation and rendering the epithelial cells susceptible to genetic damage through induction of...

Sources of Error for the Pap Smear Sampling Errors

Sampling errors account for 50-60 of false-negatives in which abnormal cells are not present on the smear either because they were not present in the collected sample or they were present but not recovered when the smear was prepared. Liquid-based cytology techniques enhance the recovery of abnormal cells collected in the cervical sample, and with reported false-negative rates of 5-15 (5,6), they are more sensitive than the conventional Pap smear in detecting SILs. Screening Errors In 1996, new technologies and techniques were emerging that were designed to improve recognition of missed cells, increase the sensitivity of the Pap smear, and reduce false-negatives. These included liquid-based cytology, automated processing and screening, automated and manual rescreening of both negative Pap smears and smears showing ASC-US, and rapid rescreening. However, these techniques were expensive, and because the increased costs were not offset by higher reimbursement, few laboratories were able...

Recommended Strategies for Alerting Physicians to the Pap Smears Inherent False Negative Rate

The following are recommended strategies for alerting physicians to the Pap smear's inherent false-negative rate 1. Include a statement in the Pap smear report reminding the clinician (and patient) that the Pap smear is a screening test with an irreducible false-negative rate, the consequences of which can be minimized by obtaining an annual Pap smear. It is important to educate the public, primary care physicians, and gynecologists about the limitations of the Pap smear so that they have realistic expectations about its sensitivity and understand why it is important to obtain a Pap smear annually. 2. Provide the referring physician with patient information cards explaining in easy to understand lay terms that although the conventional Pap smear's accuracy in detecting abnormalities is about 70-80 , it is not perfect, and, therefore, an annual Pap smear is important. The patient may be asked to sign the card to indicate that it has been read. (TDC sent such a poster containing this...

An Annual Pap Smear is Important

Acceptable and are detected by subsequent specific (and expensive) testing. False-negatives are undesirable because patients with disease will be missed. As a screening test for cervical cancer detection, the Pap smear is largely responsible for the 70 decline in deaths from cervical cancer that has occurred over the past 50 years (from 30 to 2.6 cases per 100,000 population). Yet, ironically, the Pap smear falls far short of the ideal 100 sensitivity of a screening test. Although there is a wide range in the reported false-negative rate for a single conventional Pap smear, 15-25 is widely accepted (including both sampling and laboratory false-negatives). A 20-30 false-negative rate has been reported for biopsy-proven HSIL cancer when Pap tests showing at least ASC-US are considered positive (5). Sampling false-negatives (absence of abnormal cells on the smear) are slightly more common than laboratory false-negatives, which are divided about evenly between screening errors made by...

Legal and Regulatory Considerations Affecting Pap Smear Liability

The following are legal and regulatory considerations affecting Pap smear liability 1. CLIA 88 requires a 5-year look back at prior negatives when a Pap smear shows HSILs or carcinoma. An amended report must be issued and the referring physician notified if a changed diagnosis would affect patient care. Would affect patient care, means at the current time (Health Care Financing Administration's interpretation), not at the time of the original diagnosis. Therefore, issue an amended report only if it affects current patient care, and issue it under the current accession number and not under the original accession number. This will ensure that the physician currently responsible for managing the patient's care is informed. Also, although one should rescreen the prior negatives thoroughly, avoid speculative interpretation of questionable findings (e.g., ASC-US). 3. Make cytologic-histologic correlation statements in the report only if it affects patient care. Otherwise, it is preferable...

Cancers Linked To Hpv Infections

Initial identifications of human papillomaviruses in human cancers were made in squamous cell carcinomas of the skin of patients with a rare hereditary disorder, epi-dermodysplasia verruciformis (38). Jablonska and co-workers considered this condition already in 1972 (11) as a model to study the role of papovaviruses in human cancers. A very common human cancer presently known to be caused by specific papillo-mavirus types is cancer of the cervix. The link of this cancer to HPV infections was proposed between 1974 and 1976 (15,16). The first virus isolates from this tumor type, HPV-16 and HPV-18, were published in 1983 and 1984 (19,20). Today 95 Besides cervical cancer other anogenital cancers (anal, perianal, vulval, penile, and vaginal) have been linked to the same infections. Whereas anal and perianal cancers reveal a similar distribution of high-risk HPV infections, as found in cervical cancer, only about 50 of the other cancers turn out to contain high-risk HPV DNA. It is...

Inverted Papilloma

Inverted Papilloma

Fig. 15.34a, b Endoscopic appearance of inverted papilloma, which can also look like inflammatory polyps. Fig. 15.34a, b Endoscopic appearance of inverted papilloma, which can also look like inflammatory polyps. Fig. 15.35a Coronal CT scan of extensive inverted papilloma tive coronal (c) and axial (d) CT scans after an endoscopic me-of the left paranasal sinuses. b Postoperative endoscopic view dial maxillectomy. showing a left endoscopic medial maxillectomy. c, d Postopera- Fig. 15.35a Coronal CT scan of extensive inverted papilloma tive coronal (c) and axial (d) CT scans after an endoscopic me-of the left paranasal sinuses. b Postoperative endoscopic view dial maxillectomy. showing a left endoscopic medial maxillectomy. c, d Postopera- is possible to remove all macroscopic disease. This is one circumstance when the edict that mucosa should be preserved at all costs does not apply, and success is influenced by the ability to remove all the diseased mucosa. It is now recognized that...

Contributors to Medical Morbidity in Schizophrenia

There are ample data suggesting that, overall, the quality of preventive care received by patients with schizophrenia is inferior to that of other groups, including those with other mental disorders. Druss and colleagues studied a database comprising 88,241 Medicare patients age 65 years and older hospitalized with clinically confirmed acute myocardial infarction (MI) to examine the quality of follow-up care for persons with mental disorders (Druss et al. 2001a). In their model comparing patients with specific psychiatric disorders with the rest of the population, patients with schizophrenia had a 34 increased risk of mortality in the year after hospital discharge for acute MI, whereas those with affective disorders had only an 11 increase. After the model was adjusted for quality measures and the covariates employed in the previous model, the association between mental disorders and 1-year mortality was no longer significant (P 0.17), implying that inadequate provision of standard...

Lucky Day For Two Neuropathologists And More Luck On A Sabbatical

And we could not believe our luck and kidded about the influence of the Bacardi. After Dr. Chou developed the first photographic plates that also revealed scattered virions and filamentous forms, we hugged in the dark room what an exciting day in our lives it was. Whereas the tissue in general showed moderate autolysis, the virions were so well preserved that their images compared favorably with those in the literature. The virions belonged to an identifiable group, with oncogenic potential, perhaps explaining the bizarre shapes of as-trocytes, and this virus had penetrated deep into the brain, unlike papilloma viruses. Yet no human polyoma virus was known at that time. When we showed the plates to Dr. Angevine, his dry comment was ''This is the way discoveries are being made.''

The Selling Of The Apples Acceptance Collaborations And Invitations

Well, our ''apples'' sold fast and widely. Science published our first paper (Zu Rhein and Chou, 1965). Dr. Zimmerman had agreed that we should not wait for the publication of the ARNMD volume, which indeed became delayed for 4 years. A neighbor in the Bronx was Dr. Ludwik Gross, Director of the Cancer Research Unit of the VA Medical Center. A pioneer in virus research, he had stood at the cradle of the polyoma virus. Some of his work had also been met with disbelief early on. He was a virologist well versed in viral morphology. When he reviewed our PML electron micrographs, he shared our interpretation with enthusiasm. He invited me subsequently to join him in a research seminar on ''Viruses in Disease.'' We stayed in close contact for the later editions of the Oncogenic Viruses. Dr. Richard Shope (Rockefeller University), discoverer of the rabbit papilloma virus, also became an immediate supporter during a laboratory visit. ''You are in business'' he told me with confidence and true...

Recombinant DNA Technology

The discovery of restriction endonucleases and the recognition of other enzymes involved in DNA synthesis (polymerases, ligases, transferases) opened the possibility of deliberately introducing specific foreign DNA sequences into DNA molecules. When the recombinant molecules replicate, there is a corresponding amplification of the foreign DNA. The process is called molecular cloning. When the inserted DNA is placed in frame with appropriate upstream and downstream regulatory sequences it is expressed, that is, the polypeptide specified by the foreign DNA is produced. Expression is usually achieved by incorporating the foreign DNA into a bacteriophage or a bacterial plasmid (Fig. 4-2), which serves as a cloning and expression vector when introduced into the appropriate prokaryotic or eukaryotic cells. Vectors are available that replicate in bacteria, yeasts, insect and animal cells, and in intact animals. For animal cells, a variety of animal viruses are used as vectors, notably SV40,...

The Start Of A Collaboration

Gabriele Zu Rhein clearly wanted to see this virus cultivated and characterized. She had demonstrated its presence in oligodendrocytes in PML brain tissue. The logical next step was to cultivate and identify it in order to study its role in nervous system disease. She wanted to have a part in that process, but she did not have the virology laboratory or virology background to do this, so she began prodding me to take it on in a collaborative project. I had a virology laboratory in the Department of Medical Microbiology in the same building but one floor below the Department of Pathology and Gabriele's electron microscope suite. Gabriele and I had co-authored a paper in 1956 concerned with a virus infection, but had not worked together in the interim. I had been studying persistent, chronic viral infections in cell cultures and animals and also was in the middle of a study of myxoma and fibroma virus infections. I had no experience with polyomaviruses, but I had some experience with...

The Other Side of the Coin

Immunostimulating properties of IL-10 have been shown in several in vitro and in vivo models. Leukocyte recruitment is enhanced by IL-10 via both chemotaxis45-47 and induction of endothelial cell adhesion molecule expression.48-50 Also in this case, a differential effect on T cell subsets has been reported, only CD8+ cell migration being increased by IL-10.21,45 Even original properties suggested for this cytokine, such as inhibition of APC function, T cell proliferation and Th1 type cytokine secretion have been revisited in the context of the immune response to human papilloma virus-related cervix carcinoma.51 In this tumor model IL-10 synergistically enhances IL-2-induced in vitro expansion of tumor specific CTL and cytotoxic activity. Other investigators have reported similar results,52-56 all of them underscoring the preferential activation of CD8+ T cells.

Specific Complications

Inverted Papilloma The removal of inverted papilloma justifies particular counseling. First, after removal of the lesion as completely as the surgeon is able to achieve macro-scopically, histology may show the presence of atypia or malignancy. If this is the case, a further, more radical procedure maybe required. Second, as the surgeon should aim to remove all the diseased mucosa (unlike in most other endoscopic sinus surgery procedures that preserve mucosa), there is an increased risk of stenosis, particularly in the frontal recess. A rare complication is local osteitis caused by exposure of bone. This is akin to a dry socket after a dental extraction. It produces a dull, severe nagging ache that lasts for 10 days before abating. Major analgesics are required, and local treatment appears to provide little help. Patients are particularly at risk of this in surgery for inverted papilloma where mucosa is not preserved.

Immunological Role of Dendritic Cells in Cervical Cancer

Cervical cancer is the second most frequent gynecological malignancy in the world. Human papillomavirus (HPV) infection is the primary etiologic agent of cervical cancer. However, HPV alone is not sufficient for tumor progression. The clinical manifestation of HPV infection depends also on the host's immune status. Both innate and adaptive immunity play a role in controlling HPV infection. In untransformed HPV-infected keratinocytes, the innate immunity is induced to eliminate the invading HPV pathogen through sensitization to HPV-related proteins by epithelial-residing Langerhans cells (LCs), macrophages, and other immune cells. Once the HPV infection escapes from initial patrolling by innate immunity, cellular immunity becomes in charge of killing the HPV-infected keratinocytes of the uterine cervix through systemic immune response developing by dendritic cells (DCs) in the regional lymphoid organs or through local immune response developing by LCs in the cervix. Thereby,...

Langerhans Cells in Cervical Neoplasia

Many studies have addressed the potential role for LCs in HPV infection or associated malignancy. A number of observations have shown that LCs in HPV lesions may be quantitatively reduced and functionally impaired, which may contribute to the persistence of infection (Viac et al. 1990 Scott et al. 2001 Hubert et al. 2005 Walker et al. 2005). Analysis of cervical biopsies revealed that the number of LCs was significantly reduced in intraepithelial neoplasia (Morris et al. 1983 Tay et al. 1987 Hawthorn et al. 1988 Barberis et al. 1998 Connor et al. 1999 Guess and McCance 2005). Immunolabeling of cervical epithelial sheets, prepared from fresh cervical biopsies with antibodies to the three LC markers (MHC-II, CD 1a, and Langerin), revealed reduced (to approximately 50 for the three markers) frequency of LCs in samples from HPV-infected patients compared with samples from controls (Jimenez-Flores et al. 2006). Immunostaining of formalin-fixed, paraffin-embedded tissue sections of cervical...

Pathogenic Mechanisms

The low efficiency of HPV immortalization, but even more so the recessive nature of immortalized cells, frequently complementing each other to senescence when cells of different clones are subjected to somatic cell hybridization (94,95), strongly suggests that E6 E7 gene expression is necessary but not sufficient for immortalization. The same accounts for malignant conversion as previously discussed, viral oncogene expression appears to be necessary for the malignant phenotype of HPV-positive cells. Yet, somatic cell hybridization of cells from different HPV-positive lines reveals three possible modes of outcome (96) besides the failure to complement as seen for some lines (e.g., the HPV-18-positive HeLa and SW 756 cells), some complement each other for senescence (Rosl and zur Hausen, unpublished data), and still others complement each other for a nonmalignant phenotype (e.g., HeLa cells and the HPV 16-positive Caski line). Complementation to senescence on the one hand and...

Mechanisms Of Interaction Between Hiv And

The increase in anogenital HPV infection and SIL in HIV-infected patients may be explained by several interactions between HIV and HPV, which are depicted schematically in Fig. 1. The observation of increased CSIL in patients who are iatrogenically immunocompromised or who have HIV infection underscores the role of the immune response to HPV infection. At the systemic level, it is speculated but not proven that HIV infection leads to generalized loss of memory T-cell subsets, among which may be HPV-specific clones. If true, loss of these cells this would partially account for the increased prevalence of HPV infection and SIL in HIV-infected patients.

Anal Cancer And Its Precursors

Unlike cervical HPV infection which declines substantially in prevalence after the age of 30, anal HPV infection is found in a large proportion (61 ) of MSM well into their 30s and 40s (111,112). Anal HPV infection is even more common in HIV-positive MSM, with nearly all such individuals having one or more HPV types. Infection with multiple HPV types is common, and the mean number of types increases with HIV positivity and lower CD4 levels. Several studies have examined anal HPV infection in women (44,113). Surprisingly, these studies demonstrate that anal HPV infection is found at a similar or higher rate as cervical HPV infection, and the spectrum of HPV types is similar in the anal canal and cervix. Notably, the same HPV types were found in the anus and cervix in only 50 of the women who were infected at both sites. The mode of acquisition of anal HPV infection was not clearly linked to receptive anal intercourse in these studies, but a more recent study of a larger number of women...

Issues Often Raised in Court

The following are some issues that may be raised in litigation involving Pap smears 1 Failure to adhere to current CLIA 88 regulations and or to follow practices recommended by professional societies. This may include screening Pap smears in locations other than the laboratory premises or violating workload standards. Workload standard violations may include 3. Failure to recognize that a Pap smear is unsatisfactory for evaluation.

Long Term Solutions and Questions to Explore

Define a new standard of care for the Pap smear. The zero-error standard is not attainable. We need a reasonable practitioner standard or a process standard, not an outcome standard following the procedures proven to minimize the false-negative rate (complying with CLIA 88 regulations is a minimum standard) should become the standard of care rather than the current unattainable standard of having a zero false-negative rate. 3. Identify how to effectively respond to misleading testimony given by a plaintiff's expert witness. The Guidelines for Review of PAP Smears in the Context of Litigation or Potential Litigation (a state and national professional society-endorsed process for objective slide review) are recommended (11). 6. Determine if laboratories with low volumes (

Tumor Suppressor Genes

In contrast to the growth-promoting activity of oncogenes, tumor suppressor genes constitute a growth inhibitory system. When these genes are deleted, altered, or mutated, the growth-constraining action is removed and cells may become neoplastic and exhibit uncontrolled growth. Inactivation of tumor suppressor genes is frequently observed in both malignant transformations and tumor progression. Some tumor suppressor genes are associated with the regulation of signal transduction while others are of major importance in the regulation of the cell cycle (Table 4.5). Loss (by deletion of chromosome 17) or mutation of the p53 tumor suppressor gene results in the elimination or production of a protein (53 kDa molecular mass) that is structurally altered (one amino acid replaced by another in a missense mutation) in more than half of all human malignancies. The p53 protein may also be inactivated (degraded) by its interaction with some other protein, e.g., an oncoprotein from the human...

Types of Immune Response

As a malignant tumor develops, the host is interacting with tumor-associated antigens (TAAs), the nature of which may change continuously. Examples of antigens associated with human malignancies include (a) oncofetal antigens, e.g., carcinoembryonic antigen (CEA) in colorectal and pancreatic carcinoma, and a-fetoprotein in primary liver and some testicular and ovarian cancers (b) viral antigens, e.g., hepatitis B in primary liver cancer, Epstein-Barr in Burkitt's lymphoma, and human papilloma viruses in cervical carcinoma and (c) other antigens, e.g., prostate-specific antigen and prostatic acid phosphatase in prostatic cancer, and certain glycopro-teins in solid tumors. Mass spectrometric aspects of relevant antigens are discussed in Chapter 6.

Hpv And Schistosomiasisassociated Bladder Cancer

Cooper et al. (77) examined the human papillomavirus (HPV) DNA status in schistosomal associated squamous cell carcinoma of urinary bladder in South Africa by using nonisotopic in situ hybridization (NISH) and polymerase chain reaction (PCR) against 6, 11, 16, 18, 31, and 33 genotypes. None of the cases was shown to harbor HPV DNA. This study abrogates the role of HPV in schistosoma-associated bladder cancer in South Africa. Other factors including nitrosamine exposure, p53 mutations, and additional unknown chromosomal events may play a major role in the development of this parasite-associated neoplasm.

Preadministration Assessment

Before administering an estrogen or progestin, the nurse obtains a complete patient health history, including a menstrual history, which includes the menarche (age of onset of first menstruation), menstrual pattern, and any changes in the menstrual pattern (including a menopause history when applicable). In patients prescribed an estrogen (including oral contraceptives), the nurse obtains a history of thrombophlebitis or other vascular disorders, a smoking history, and a history of liver diseases. Blood pressure, pulse, and respiratory rate are taken and recorded. The primary health care provider usually performs a breast and pelvic examination and obtains a Pap smear before starting therapy. He or she may also order hepatic function tests.

Viruses And Malignancy

Peyton Rous

In 1933 Shope reported a rabbit papilloma that was also transferable via a cell-free mechanism (148). This tumor was to become the subject of intense study in the years to follow. The agent responsible was eventually found to be a DNA virus, subsequently labeled papillomavirus (149). Rous' first report of his work with the Shope papilloma was published in 1934. He had given up work on fowl viruses several years before, probably because of the slow acceptance of his research by those who were sure that cancer could not be caused by In the first of their two initial articles on the Shope virus, Beard and Rous confirmed the malignant potential of the tumor, and noted that the virus is recoverable from the tissue. They also noted that papillomas of the skin are transmittable through virus inoculation, and that these growths proliferate actively as a rule and frequently cause death (155). In their second article on the subject, Beard and Rous reported that injection of a chemical solution...

Arrival Of Pml Cases And An Electron Microscope

Multifocal Microscopy

Another interdisciplinary contact, which became of considerable importance later on, developed with Veterinary Science. In this Department, Dr. Carl Olson had created a research unit for the study of papilloma viruses, especially of bovine and canine types. A viral oncologist who appreciated the contributions of morphology, he early had acquired an electron microscope. My affiliation with Veterinary Science began in 1957. All such students had to do course work in pathology, and I became their instructor in neuropathology. Over the years I served on at least nine examination committees for M.S. or Ph.D. In May 1964, another of Dr. Olson's students took his Ph.D. examination, and I was a thesis reader. Among the illustrations for The Cytology of Canine Oral Papilloma'' were electron micrographs of cell nuclei with dispersed or aggregated virions. Listed among the references was Dr. Melnick's paper in Science (1962) entitled Papova Virus Group.'' In it, he combined the papil-loma and...

Uterine Leiomyomas And Stenosis Of The Right Oviduct

M.T., a 60-year-old gravida 2, para 2, had spent 3 months under the care of her gynecologist for treatment of postmenopausal bleeding and cervical dysplasia. She had had several vaginal examinations with Pap smears, a uterine ultrasound, colposcopy with endocervical biopsies, and a D&C with cone biopsy. She wanted to take hormone therapy, but her doctor thought she was at too much risk with the abnormal cells on her cervix and the excessive bleeding.

Antrochoanal Polyp Ct

Nasal Polyp

Two additional signs are described as common features of sinonasal polyposis. (1) Widening of ethmoid infundibulum can be observed in several different conditions, including antrochoanal polyp and inverted papilloma. The specificity of this finding, however, is increased by bilateral presentation. (2) Truncation of middle turbinate (bilateral in up to 80 of cases) is easily recognized on CT scans as an amputation of the more distal, bulbous part, the vertical lamella usually being spared. In a series of 100 patients (LiANG et al. 1996) affected by chronic rhinosinusitis, this sign was observed exclusively in the subgroup with sinonasal polyposis, in 58 of cases.

Complications Of Frontal Sinus Osteoma

Pyogeni Brast

Laryngol Otol 95 291-304 Bachor E, Weber R, Kahle R et al (1994) Temporary unilateral amaurosis with pneumosinus dilatans of the sphenoid sinus. Skull Base Surg 4 169-175 Bajaj MS, Pushker N (2002) Inverted papilloma invading the Benninger MS, Marks S (1995) The endoscopic management of sphenoid and ethmoid mucoceles with orbital and intracranial extension. Rhinology 33 157-161 Berlucchi M, Piazza C, Blanzuoli L et al (2000) Schwannoma of the nasal septum a case report with review of the literature. Eur Arch Otorhinolaryngol 257 402-405 Bernier JL, Bhasker SN (1958) Aneurysmal bone cyst of mandibula. Oral Surg 11 1018 Bielamowicz S, Calcaterra TC, Watson D (1993) Inverting papilloma of the head and neck the UCLA update. Otolaryngol Head Neck Surg 109 71-76 Blitzer A, Kalmon D, Conley J (1989) Craniofacial resection of ossifying fibromas and osteomas of the sinuses. Arch Otolaryngol Head Neck Surg 115 1112-1115 Bloom DC, Finley JC Jr, Broberg TG et al (2001) Leiomyoma of Brandwein M,...

Tumor Antigens May Be Induced by Viruses

The Cardiac Cycle Steps

For example, when syngeneic mice are injected with killed cells from a particular polyoma-induced tumor, the recipients are protected against subsequent challenge with live cells from any polyoma-induced tumors (see Table 22-2). Likewise, when lymphocytes are transferred from mice with a virus-induced tumor into normal syngeneic recipients, the recipients reject subsequent transplants of all syngeneic tumors induced by the same virus. In the case of both SV40- and polyoma-induced tumors, the presence of tumor antigens is related to the neoplastic state of the cell. In humans, Burkitt's-lymphoma cells have been shown to express a nuclear antigen of the Epstein-Barr virus that may indeed be a tumor-specific antigen for this type of tumor. Human papilloma virus (HPV) E6 and E7 proteins are found in more than 80 of invasive cervical cancers the clearest example of a virally encoded tumor antigen. Consequently, there is great interest in testing as vaccine candidates the...

Choroid plexus tumors

Choroid plexus tumors, including choroid plexus carcinoma and choroid plexus papilloma, account for 1-3 of all pediatric brain tumors generally present during the first two years life.69 71 Extensive disease, including leptomeningeal metastases, has been reported in up to 70 of infants with choroid plexus carcinoma. Multi-modality therapy with surgery, chemotherapy, and radiation has been effective for some patients. The efficacy of adjuvant therapy in terms of both chemotherapy and radiotherapy remains unclear due to limited data.69 However, it appears that CSI is a

Identification Of A New Virus

Polyomavirus

On October 7, 1970, a midstream urine sample, collected a day earlier, arrived in the laboratory from a Sudanese patient who had received a renal transplant from his brother on June 24, 1970. A phone call the same day from St. Mary's Hospital informed us that this urine contained many inclusion-bearing cells, and so electron microscopy examination would be well worthwhile. Two days later, Anne Field saw very large numbers of papovavirus particles in the high-speed urine pellet and suggested that they were particles of common wart virus (the only human papovavirus known at the time). It was queried whether the patient had genital warts a report earlier that year (Spencer and Andersen, 1970) had described a high incidence of warts after renal transplantation. Ultrathin sectioning of the cells in a subsequent urine sample collected on October 12 from the same patient showed many virus particles within enlarged cell nuclei. Measurement of the virus particles (45 nm diameter) showed the...

Cancer of the Female Reproductive Tract

Oophorectomy

Almost all patients with cancer of the cervix have been infected with human papilloma virus (HPV), a virus that causes genital warts. Incidence also is related to high sexual activity and other sexually transmitted viral infections, such as herpes. Cervical carcinoma is often preceded by abnormal growth (dysplasia) of the epithelial cells lining the cervix. Growth is graded as CIN I, II, or III, depending on the depth of tissue involved. CIN stands for cervical intraepithelial neoplasia. Diagnosis of cervical cancer is by a Pap smear, examination with a colposcope, and biopsy. In a cone biopsy (Fig. 15-10), a cone-shaped piece of tissue is removed from the lining of the cervix for study. Often in the procedure, all of the abnormal cells are removed as well.

David B Troxel md fcap

This chapter reviews The Doctors Company experience with medical liability claims involving the Pap smear. The historical factors leading to the explosive growth in Pap smear litigation are discussed and an expert medical panel's analysis of the sources of error in the Pap smear are presented in detail. The panel's recommendations for reducing the Pap smear's inherent false-negative rate, thereby decreasing patient injury from missed cervical cancers and their precursors, are reviewed. Finally, new technologies and strategies that enhance the Pap test's sensitivity (liquid-based cytology and DNA testing for human papillomavirus) are presented. Key Words Pap smear liability Pap smear sensitivity Pap smear false-negative rate cervical cancer human papillomavirus liquid-based cytology. During the 1990s, both the frequency and severity (average indemnity paid per allocated claim) of claims involving cervical cytology (Pap smears) increased dramatically and became the most important source...

Screening And Treatment Algorithms For Anal Hsil

The data presented here indicate a high prevalence of ASIL among both HIV-positive and HIV-negative MSM, as well as a high incidence of HSIL and a high incidence of anal cancer among both HIV-positive and HIV-negative MSM. Given the similarity between cervical and anal cancer, it is possible that an anal cytology screening program in high-risk populations may reduce the incidence of anal cancer, similar to the reduction in cervical cancer associated with implementation of cervical cytology screening. As proposed, screening would be considered for the men and women at highest risk, that is, those with a history of receptive anal intercourse. Sexually active women, particularly those who are HIV-positive or who have a history of cervical HSIL or vulvar cancer, also appear to be at increased risk of anal HPV infection and ASIL. Thus, other risk groups that could be considered for screening include all HIV-positive women, regardless of whether or not they have engaged in anal intercourse,...

Treatment Of Cervical

As described previously, the first step in the workup of CSIL is performance of cervical cytology. If an abnormal cytology has been obtained, the two major decision points in the management algorithm for treatment of CSIL are (1) whether or not to perform colposcopy and (2) whether or not treat a cervical lesion once it has been biop-sied and the histopathology of the lesion has been established. A number of different organizations have published guidelines for cervical cytology screening in women. The American College of Obstetricians and Gynecologists and the American Cancer Society recommend that all women begin yearly Pap tests at age 18 or when they become sexually active, whichever occurs earlier. If a woman has had three consecutive negative annual cytology tests, testing may be performed less often at the judgment of a woman's health care provider. Once a decision to treat CIN is made and biopsies have excluded invasion, there are a number of therapeutic options. Because there...

Create Subgroups with Accurate Ascertainment or Non Differential Underascertainment

Estrogens Endometrial Cancer Hulka

For a number of reasons, accurate ascertainment of disease may be unattainable for the entire study population. There may be subgroups within the study population, however, in which disease ascertainment is accurate. Some diseases are largely asymptomatic, for example carcinoma in situ of the cervix, but among women who obtain annual Pap smear screening the diagnosis is likely to be virtually complete. Valid results can therefore be obtained within the subset of the population in which ascertainment is complete, in this instance among women who obtain annual screening. The potential disadvantage of this approach is that the marker of completeness of ascertainment may well be a marker of other factors that affect the occurrence of disease. That is, the attributes required to have complete diagnosis may also be true modifiers of the effect of interest. If obtaining regular Pap smear screening acts as a modifier of the risk factor under investigation, then the stratum-specific result...

Functional Interactions Between Hpvs And Keratinocytes

Models of HPV Infection and Disease Transformation of human skin was first demonstrated for HPV-11, a condylomata acuminata associated HPV type. HPV-11 viral particles were used to infect human skin that then was grafted beneath the renal capsule of athymic mice (126,127). This resulted in production of viral particles and the development of condyloma similar to those seen in patients (128). Such xenograft models were subsequently improved by the use of severe combined immunodeficiency (SCID) mice, producing larger xenografts that showed an increased rate of HPV-11 positivity (129). This work was extended to include engraftment of HPV-16-infected foreskin keratinocytes were grafted onto the skin of SCID mice. The grafted skin expressed involucrin in differentiating keratinocytes and displayed features of HPV infection including koilocytosis and production of capsid antigen (130). Direct grafting of HPV-6 or -11-containing lesions onto the skin of SCID mice also resulted in the...

Interleukin10 and Human Cancer

Foreskin Lesions

The proliferation rate of human melanoma cell lines is enhanced by exogenous IL-10, suggesting that this cytokine might serve as a tumor growth factor.60 In addition, IL-10 immune suppressive effects may allow tumor escape from immune recognition.60-62 The role that IL-10 may play in tumor escape is, however, far from established. In the context of human papilloma virus-related cervical carcinoma, IL-10 enhances synergistically with IL-2 tumor-specific T cell expansion and cytotoxicity by increasing intracellular accumulation of perforin. 3 In a recent

Some cancers are caused by viruses

An important group of virally induced cancers among North Americans and Europeans is the various anogenital cancers caused by papillomaviruses. The genital and anal warts that these viruses cause often develop into tumors. These viruses seem to be able to act on their own, not needing mutations in the host tissue for tumors to arise. Sexual transmission of these papillomaviruses is unfortunately widespread.

Dendritic Cells In Other Nonhiv Infections

Human papillomavirus (HPV) is causally associated with cancer of the urogenital tract (56). HPV-associated proliferative skin lesions expressing abundant viral protein can persist for years in immunocompetent subjects, a property that distinguishes HPV infection from that of the lytic RNA viruses. The fact that no antibody to viral capsid proteins is detectable for 6-12 months following infection confirms the idea that HPV infection does not generate a conventional immune response. One mechanism by which this virus may suppress the generation of immunity appears to be related to their infection of Langerhans cells (DCs of the epidermis). Thus, Langherhans cells expressing the E7 protein of papillomavirus have been shown to be poor stimulators of E7-specific T-cells. Precisely how HPV inhibits DC function is unknown.

Riskmanagement issues

There is also the duty to obtain informed refusal. In 1980, the California Supreme Court (27 CAL. 3d 285) established this doctrine when it ruled for the plaintiff in the case of a woman who died of advanced cervical cancer. Her family physician's record documented that over a period of years he had repeatedly advised a routine Pap smear. However, the record did not establish that he had ever explained the reason for a Pap smear or the potential risks of not having one. The patient's family was able to successfully argue that if she had known that the purpose of a Pap smear was to detect cervical cancer, then she might have given consent.

Geneenvironment Interactions

Infectious diseases result from interactions between the host and pathogen, and understanding these diseases requires understanding not only alterations in gene and protein expressions within the infected cells but also alterations in the surrounding cells and tissues. Although genome and transcriptome analyses can provide a wealth of information on global alterations in gene expression that occur during infections, proteomic approaches allow the monitoring of changes in protein levels and modifications that play important roles in pathogen-host interactions. During acute stages of infection, pathogen-coded proteins play a significant role, whereas in the chronic infection, host proteins play the dominating role. Viruses, such as hepatitis B (HBV), hepatitis C (HCV), and human papillomavirus (HPV), are suitable for proteomic analysis because they express only eight to ten major genes.45 Analyzing a smaller number of genes is easier than analyzing the proteome of an organism with...

Preventative Measures

Provide recommendations for follow-up of Pap smears with epithelial cell abnormalities or specimen adequacy limitations, especially for nongynecologists. The 2001 Consensus Guidelines for Cervical Cyto-logical Abnormalities sponsored by the American Sociesty for Colposcopy and Cervical Pathology (ASCCP) are recommended (13). 7. Use outside expert consultation for problem Pap smears, when appropriate. 8. Restrict discussions about potential claims to individuals within your practice group. Limit the number of people within your group who review a potential problem Pap smear, because anyone who reviews it may be subsequently deposed.

Virusassociated Malignancies

Epstein Barr Virus Infection Timeline

Human Papillomavirus Infection with HPV is widespread throughout population. Over 80 strains of this virus cause a spectrum of tumors of skin and mucous membranes. HPV-1 and HPV-6 appear to be largely responsible for benign skin warts and genital warts, respectively, whereas 90 of cervical carcinomas are associated with HPV-16 and HPV-18 (69). Despite the wide involvement of HPV in sexually transmitted disease and its association with malignancy, specific therapy for HPV is still not available. Surgical or chemical removal of the wart leaves the viral episome in the basal epithelium, and host cell transformation can result from random integration of oncogenic HPV DNA into the genome (70). Prophylaxis with vaccines for genital papillomaviruses might prevent infection by eliciting neutralizing antibodies (70). To be effective, such vaccines must establish an immunologic barrier at the anogenital epithelium by selective stimulation of a secretory IgA-mediated anti-HPV virion response in...

Vital Genitourinary Infections

Two major viral sexually transmitted diseases (STD), genital herpes and genital warts, dramatically increased in frequency during the sexual revolution of the 1960s and 1970s. The painful itchy lesions of genital herpes (Fig 20-6) and the accompanying local and systemic symptoms were described in Chapter 20. Dozens of recurrences, mainly attributable to HSV-2 but increasingly to HSV-1 also, may dominate the life of the hapless carrier. Genital warts, caused most commonly by the human papillomaviruses HPV-6 and HPV-11, can take the form of prolific excrescences on the external genitalia, perineum, vaginal introitus, penis, or anus (known as condyloma accuminatum (Fig. 18-3), or the form of a less conspicuous flat lesion on the cervix (condyloma planum) they are discussed in Chapter 18. Certain oncogenic HPV types, particularly types 16 and 18, produce cervical dysplasia which may progress over the course of many years to invasive cancer the same HPV types are also eti-ologically...

Transformation And Oncogenicity

BKV, JCV, and SV40 are tumorigenic for laboratory animals, especially Syrian hamsters. The animal species, the age of the animal, the route of inoculation, and the amount of virus in the inoculum are important determinants of oncogenicity. Table 1 lists the species in which the viruses produce tumors and the histologic types of the main tumors. Brain tumors are induced by all three viruses. BKV most often produces tumors of the ventricular surfaces, such as ependymomas and choroid plexus papilloma (4,5), whereas JCV produces predominantly tumors of neural origin, such as medu-loblastoma, glioblastoma, and astrocytoma (6,7). JCV is unique among viruses in its ability to produce experimental brain tumors in primates, specifically astrocytomas in owl and squirrel monkeys (8). SV40 produces a large variety of tumors in laboratory rodents, including mesotheliomas in hamsters.

Management and Referral

Fig. 9.15 Sessile papilloma - note broad base but typical craggy surface. Fig. 9.15 Sessile papilloma - note broad base but typical craggy surface. Fig. 9.16 Pedunculated papilloma involving conjunctiva. Reproduced with permission from Kanski J J, 2003, Clinical Ophthalmology A Systemic Approach, ButterworthHeinemann. Fig. 9.16 Pedunculated papilloma involving conjunctiva. Reproduced with permission from Kanski J J, 2003, Clinical Ophthalmology A Systemic Approach, ButterworthHeinemann.

Workbook in Microbiology Laboratory Techniques 7e

Immunologic assays, such as immunofluorescence and enzyme immunoassay, are used to detect viral antigens, and nucleic acid amplification techniques are used to detect viral nucleic acids directly in patient specimens (see Exercise 19). Antigen detection assays are available for a number of different viruses including respiratory syncytial virus, herpes simplex virus, influenza A and B viruses, rotavirus, and adenovirus. Currently, nucleic acid amplification assays are limited to the detection of human papillomavirus although assays for quantifying blood levels of viruses such as HIV are available. If viral products are detected, the laboratory diagnosis of infection is established and the need to perform viral culture is eliminated. Results are often available within 10 to 60 minutes. The earliest nonculture laboratory method used for viral diagnosis was screening for characteristic changes in infected human cells and tissues. Examination of cell smears or tissue sections stained with...

Epithelial Membranes

Gynecological Epithelial Tissue

The constant loss and renewal of cells is characteristic of epithelial membranes. The entire epidermis is completely replaced every 2 weeks the stomach lining is renewed every 2 to 3 days. Examination of the cells that are lost, or exfoliated, from the outer layer of epithelium lining the female reproductive tract is a common procedure in gynecology (as in the Pap smear).

Interferons

Although the advent of less expensive interferons produced by recombinant DNA technology made it possible to treat patients with the sort of dosage that is required to produce clinically beneficial effects, it must be said that the successes are still rather modest. For example, some hepatitis C carriers respond to prolonged treatment with interferon a, but most relapse following withdrawal of the drug (Chapter 26). Genital warts have been successfully treated, and juvenile laryngeal papillomatosis, a severe condition calling for repeated surgical removal following recurrences, can be arrested by local injection of interferon however, the tumors reappear when therapy is withdrawn (Chapter 18).

Diagnostic Tests

Ulcer base), which demonstrates the presence of multinucleated giant cells with intranuclear inclusions. Cultures for bacterial, fungal, mycobacterial, and viral pathogens should be obtained where appropriate. Punch biopsy is also valuable for the investigation of chronic mucosal lesions and for the diagnosis of malignant or premalignant conditions. Immunofluorescence staining for antigen detection can also be performed for herpes simplex and varicella-zoster as well as papilloma viruses and other pathogens. Identification of potential pathogens by DNA amplification and hybridization techniques is a powerful tool that is increasingly being utilized to identify etiologic agents in suspected infections that are culture-negative.

TLR7 and TLR8

TLR7 and TLR8 have been shown to recognize viral nucleic acids. Firstly, TLR7 and 8 were shown to trigger IFN production in response to the imidazoquino-lines, imiquimod, and resiquimod (or R-848). These are low-molecular-weight immune response modifiers with potent antiviral and antitumor properties that are used clinically in the treatment of external genital warts caused by human papilloma virus infection (Hemmi et al. 2002). Using MyD88 and TLR7 knockout mice, Hemmi et al. showed that the imidazoquinolines activate murine immune

Conclusions

Prevention of cervical cancer through cervical cytology screening depends on identification and treatment of cervical HSIL before it progresses to cancer. Several methods such as monolayer cervical cytology, computerized screening of cervical smears, and adjunctive HPV testing will likely improve the diagnostic sensitivity and specificity of cervical cytology screening in a cost-effective manner. Advances in therapy for HPV-associated lesions have been slower in coming, but promising new HPV-specific approaches include therapeutic vaccines targeted at HPV antigens. Patients coinfected with HPV and HIV infection present a special challenge to the clinician owing to higher prevalence of CSIL and lower success rates with standard therapy. The HIV epidemic has also brought increased attention to the clinical problem of ASIL and anal cancer. Although the risk of these lesions is highest among MSM, women are also at risk, particularly those with a history of receptive anal intercourse and...

Frontal Sinus

Fig. 15.50 a Preoperative and b postoperative endoscopic views of recurrent inverted papilloma in the left maxillary sinus extending around the floor and anterior wall. Fig. 15.50 a Preoperative and b postoperative endoscopic views of recurrent inverted papilloma in the left maxillary sinus extending around the floor and anterior wall.

Ongoing Assessments

At the time of each office or clinic visit, the nurse obtains the blood pressure, pulse, respiratory rate, and weight. The nurse questions the patient regarding any adverse drug effects, as well as the result of drug therapy. For example, if the patient is receiving an estrogen for the symptoms of menopause, the nurse asks her to compare her original symptoms with the symptoms she is currently experiencing, if any. The nurse weighs the patient and reports a steady weight gain or loss. A periodic (usually annual) physical examination is performed by the primary health care provider and may include a pelvic examination, breast examination, Pap smear, and laboratory tests. The patient with a prostatic or breast carcinoma usually requires more frequent evaluations of response to drug therapy.

Can Nasal Polyps

Angiomatous Polyp

Inverted papilloma arising from the maxillary sinus has to be distinguished from antrochoanal polyp, fungus ball, and from malignant neoplasms (Savy et al. 2000). On CT, fungus balls may show findings comparable to those of inverted papilloma, namely remodeling and destruction of the medial antral wall and discrete densities within the lesion. They are easily differentiated on MR because almost totally hypoin-tense on T2 sequences. The differential diagnosis is more complex for inverted papilloma presenting as a unilateral nasal mass. Of course, sinonasal polyposis typically involves both nasal cavities therefore the detection of a unilateral polypoid lesion in the adult raises the suspicion of inverted papilloma among other benign and malignant neoplasms.

Neoplasia

AIDS-associated malignancies are a major complication associated with AIDS patients on immunosuppression 140 . Three cancers are considered an AIDS-defining neoplasm (1) Kaposi's sarcoma, (2) high-grade B-cell non-Hodgkin's lymphoma, and (3) invasive cervical cancer 141 . Before the introduction of HAART, non-Hodgkin's lymphoma represented one of the most prevalent causes of neoplasia in HIV-infected people 142145 . The incidence of Kaposi's sarcoma and non-Hodgkin's lymphoma, have fallen sharply since the advent of HAART, as a result of immune restoration rather than of a specific effect on the tumoral process 146 . Recent epidemiologic studies have identified higher rates of non-AIDS-defining neoplasia carcinoma of the anus, lung, breast, skin, conjunctiva, liver, and prostate in HIV-positive patients 147 . The role of HIV-induced immu-nosuppression in the development of non-AIDS-defining cancers seems less important than lifestyle habits like smoking and sun exposure, and...

Alpha Defensins

Mucosa is inversely correlated to the incidence of HPV infection and cervical cancer incidence (Buck et al. 2006). HNP1-4 have antiviral effects against many viruses including HIV1 (Klotman and Chang 2006). Furthermore, deficiencies in these alpha defensins are also associated with an increased incidence of inflammatory bowel disease (IBD) (Wehkamp and Stange 2006). We have found alpha defensins to be chemotactic for the subset of CD4+ CD45+ RA+-naive T cells, some CD8+ T cells, and immature DCs (Chertov et al. 1996 Yang et al. 2000, 2004a). Although this chemotactic effect is PTx inhibitable, the specific HNP receptor has not been identified. Alpha defensins also activate immature DCs (iDCs) to mature into mDCs. This is characterized by phenotypic changes such as increased expression of CD80, CD83, CD86, CD40, and MHC class II, increased production of inflammatory cytokines, and loss of receptor expression such as CCR1 and 5 but an increase in the expression of CCR7. Mature DCs also...

Podophyllum

Podophyllin Resin

Podophyllum resin has long been used as a purgative, but the discovery of the cytotoxic properties of podophyllotoxin and related compounds has now made podophyllum a commercially important drug plant. Preparations of podophyllum resin (the Indian resin is preferred) are effective treatments for warts, and pure podophyllotoxin is available as a paint for venereal warts, a condition which can be sexually transmitted. The antimitotic effect of podophyllotoxin and the other lignans is by binding to the protein tubulin in the mitotic spindle, preventing polymerization and assembly into microtubules (compare vincristine, page 356, and colchicine, page 343). During mitosis, the chromosomes separate with the assistance of these microtubules, and after cell division the microtubules are transformed back to tubulin. Podophyllotoxin and other Podophyllum lignans were found to be unsuitable for clinical use as anticancer agents due to toxic side-effects, but the semi-synthetic derivatives...

Nipple discharge

A small amount of clear fluid expressed from multiple ducts of the breast on massage is normal. Persistent single duct discharge or blood-stained (macroscopic or microscopic) discharge should always be investigated. The differential diagnosis includes duct ectasia, intraduct papilloma or rarely intraduct carcinoma.

Rna Viruses

Papovaviridae Diseases Caused

Genus Papillomavirus (papillomaviruses) Genus Potifonmvirus (polyomaviruses) The papovaviruses sigla, from papilloma, polyoma, vacuolating agent (early name far SV40) are small nonenveloped icosahedral viruses which replicate in the nucleus and may transform infected cells. In the virion the nucleic acid occurs as a cyclic double-stranded DNA molecule, which is infectious. There are two genera. Virions of Papillomavirus (wart viruses) are 55 nm in diameter and have a larger genome (8 kbp) which may persist in transformed cells in an episomal form. Virions of members of the genus Poly-own virus are 45 nm in diameter, have a smaller genome (5kbp), and may persist in cells via the integration of their genome into the host cell DNA. Human papillomaviruses cause warts, and some of the several dozen types are associated with cancer of the cervix or the skin the human polyomaviruses usually cause inapparent infections but may be reactivated by immunosuppression Murine polyoma virus and...

Ebv Hcmv

The effects of viral infection on the transcriptome of cells in vitro and in vivo has been determined for viruses as diverse as retroviruses, herpesviruses, orthomyxoviruses, enteroviruses, adenoviruses, hepatitis B and C viruses, and papilloma viruses. These initial studies show that viruses cause both common and unique changes in cellular gene expression profiles during their replication cycle (Fruh et al 2001, Kellam 2000, 2001). However, the degree of host

Haematuria

Haematuria Colours

Painless haematuria in the aduli is usually due to a benign bladder papilloma or to renal, bladder or prostatic carcinoma. Haematuria associated with severe loin pain suggests a renal or ureteric origin, commonly due to the presence of a calculus. When haematuria is accompanied by dysuria or frequency, the source is usually in the

Health Care Issues

In New York City suggest that the situation may not be so bleak for the geriatric population. Ninety three percent of the sample of 117 outpatients had seen a physician other than a psychiatrist in the past year, and nearly three-quarters had seen their doctor in the past month (C. I. Cohen, unpublished data). The number of visits to nonpsychiatric health providers was actually somewhat greater than for the community comparison group. In addition, one-third of the sample had seen a dentist in the past year, and among women, 28 and 44 reported that in the past year they had received a pap smear and breast examination, respectively. Moreover, the percentages of persons reporting receiving medication for heart disorders, hypertension, or diabetes were 77 , 81 , and 85 , respectively. A combination of factors played a role in patients' seeking out and complying with medical treatment, including the availability of health insurance (Medicare and Medicaid in most instances), easier access...

Lasers in Urology

The most frequent malformations of the external genital are called condylomata acuminata. These benign warts must be treated as early as possible, because they tend to be very infectious and degenerating. After circumcision and application of 4 acetic acid to suspected areas, they are coagulated with either Nd YAG or CO2 lasers. Occasional recurrences cannot be excluded, especially in the treatment of intraurethral condylomata. With both laser types, however, the rate of recurrence is less than 10 as reported by Baggish (1980) and Rosemberg (1983). Hemangiomas of the external genital should be treated with radiation from Nd YAG lasers because of its higher penetration depth. Hofstetter and Pensel (1993) stated that additional cooling of the tissue surface may even improve the procedure. Carcinoma of the external genital are best treated with a Nd YAG laser if they are at an early stage. This significantly reduces the risk of having to perform a partial amputation. According to Eichler...