Persistent Human Papillomavirus Infection

Simple SummaryThe success of HPV as an infectious agent lies not within its ability to cause disease, but rather in the adeptness of the virus to establish long-term persistent infection. The ability of HPV to replicate and maintain its genome in a stratified epithelium is contingent on the manipulation of many host pathways. HPVs must abrogate host anti-viral defense programs, perturb the balance of cellular proliferation and differentiation, and hijack DNA damage signaling and repair pathways to replicate viral DNA in a stratified epithelium. Together, these characteristics contribute to the ability of HPV to achieve long-term and persistent infection and to its evolutionary success as an infectious agent.AbstractPersistent infection with oncogenic human papillomavirus (HPV) types is responsible for ~5% of human cancers. The HPV infectious cycle can sustain long-term infection in stratified epithelia because viral DNA is maintained as low copy number extrachromosomal plasmids in the dividing basal cells of a lesion, while progeny viral genomes are amplified to large numbers in differentiated superficial cells. The viral E1 and E2 proteins initiate viral DNA replication and maintain and partition viral genomes, in concert with the cellular replication machinery. Additionally, the E5, E6, and E7 proteins are required to evade host immune responses and to produce a cellular environment that supports viral DNA replication. An unfortunate consequence of the manipulation of cellular proliferation and differentiation is that cells become at high risk for carcinogenesis.     

Syncope and Headache

Purpose of Review

We review the literature on co-occurrence of syncope and headache and share clinical experience.

Recent Findings

Headache in relation to syncope has been the subject of recent interest.

Summary

Orthostatic intolerance has an expanding spectrum with three well-defined entities: orthostatic hypotension (OH), neurally mediated hypotension (NMH), and postural tachycardia syndrome (PoTS). Syncope occurs in patients with OH as well as in patients with episodically occurring NMH. Headache of OH is called coat-hanger ache (CHA) because it affects the neck and shoulders in a coat-hanger pattern. It can serve as a warning symptom of OH as well as a parameter to gauge the benefit of treatment. Awareness of CHA avoids inappropriate tests. Headache type occurring in NMH has not been fully delineated. A questionnaire-based study describes migraine leading to syncope and treatment of migraine to reduce syncope. Laboratory studies in NMH patients provide evidence for only short-duration headache. The author’s approach to such patients is presented.

     

Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach

Tamoxifen, a selective estrogen receptor modulator, is widely used in research and clinically in patients. We find that treatment of normal mice with a single ≥3 mg/20 g body weight dose of tamoxifen leads to apoptosis of >90% of all gastric parietal cells (PCs) and metaplasia of zymogenic chief cells within 3 days. Remarkably, gastric histology returns to nearly normal by 3 weeks. Tamoxifen toxicity occurs by oral and intraperitoneal administration, in both sexes, in multiple strains, and does not depend on estrogen, though acid secretion inhibition is partially protective. Thus, substantial gastric toxicity is a heretofore unappreciated tamoxifen side effect.     

A Community and Culture-Centered Approach to Developing Effective Cardiovascular Health Messages

Objective

Little is known about how best to target cardiovascular health promotion messages to minorities. This study describes key lessons that emerged from a community and culture-centered approach to developing a multimedia, coronary heart disease (CHD) patient education program (PEP) for medically underserved South Asian immigrants.

Methods

The prototype PEP integrated the surface structures (e.g. language) and deeper structures (e.g. explanatory models (EMs), values) of South Asians'' socio-cultural context. Seven focus groups and 13 individual interviews were used to investigate South Asians’ reactions and obtain qualitative feedback after viewing the culturally targeted PEP. Qualitative data were organized into emergent thematic constructs.

Results

Participants (n = 56) mean age was 51 years and 48 % were Hindi speakers. Community members had a strong, negative reaction to some of the targeted messages, "This statement is a bold attack. You are pin-pointing one community." Other important themes emerged from focus groups and interviews about the PEP: 1) it did not capture the community’s heterogeneity; 2) did not sufficiently incorporate South Asians’ EMs of CHD; and 3) did not address economic barriers to CHD prevention. Feedback was used to revise the PEP.

Conclusion

A community and culture-centered approach to developing cardiovascular health promotion messages revealed tensions between the researcher’s vantage point of “cultural targeting” and the community’s perceptions and reactions to these messages. Engaging communities in every phase of message design, incorporating their EMs, recognizing community heterogeneity, and addressing economic and structural barriers, are critical steps to ensuring that health promotion messages reach their intended audience and achieve true cultural appropriateness.KEY WORDS: cardiovascular, health communication, Asian-American, culture, qualitative     

Epithelioid sarcoma: one institution's experience with a rare sarcoma

BackgroundEpithelioid sarcomas (ES) are extremely rare soft tissue sarcomas. As such, their clinical behavior and response to treatment are poorly described in the literature.MethodsWe queried the centralized cancer registry and pathology archives at the Johns Hopkins Medical Institution and identified 22 patients with a diagnosis of ES. We excluded two patients because of inadequate data. A pathologist reviewed patient charts and reexamined available histological slides. This study was performed with institutional review board approval.ResultsThe median age at diagnosis was 27.8 y; most patients (75%) were male. Regional lymph node metastases were present in 10% of patients at presentation. The majority of tumors (57.9%) recurred and 35% recurred more than once, although the number of recurrences did not affect survival (P = 0.48). Patients did not experience a decrease in time to recurrence with increasing number of resections. The median time between resection and recurrence was 1.23 y and the maximum was 18.8 y. Median overall survival was 56.2 mo and 5-y survival was 92%.ConclusionsOur study reveals that ES is an extremely rare tumor with a protracted and recurrent course, but overall survival may be more favorable than in the past. Patients benefit from aggressive and repeated resection. Epithelioid sarcoma is unique because it metastasizes to regional nodal basins. Extended surveillance is indicated, because recurrences can appear after decades of quiescence.