Replication ability of three highly protective Marek's disease vaccines: implications in lymphoid organ atrophy and protection

The present work is a chronological study of the pathogenesis of three attenuated serotype 1 Marek's disease (MD) virus strains (RM1, CVI988 and 648A80) that provide high protection against MD but have been attenuated by different procedures and induce different degrees of lymphoid organ atrophy. All studied strains replicated in the lymphoid organs (bursa,x thymus and spleen) and a peak of replication was detected at 6 days post inoculation (d.p.i.). Differences, however, were observed among vaccine strains. RM1 strain replicates more in all lymphoid organs compared with CVI988 and 648A80 strains. In addition, replication of RM1 in the thymus did not decrease after 6 d.p.i. but continued at high levels at 14 d.p.i. and until the thymus was completely destroyed. Lung infection occurred very early after infection with all of the three vaccines and the level of replication was similar to that found in the lymphoid organs. Infected cells were very large and appeared scattered in the lung parenchyma and in the parabronchial lining. The study of the target cells for the early infection in cell suspensions of blood and spleen showed that both non-adherent cell populations (enriched in lymphoid cells) and adherent cells (enriched in monocytes/macrophages) supported MD virus infection. Infection in adherent cells was especially high at very early stages of the infection (3 to 6 d.p.i.). Atrophy of lymphoid organs is a major drawback in the production of highly protective vaccines against MD. A better understanding of the mechanisms associated with lymphoid organ atrophy will aid in overcoming this problem.     

Relationship between earmould venting, comfort and feedback

Although earmould venting is considered to make an earmould more comfortable, whether it does so remains to be proven in hearing-aid users. A hundred and six patients were sequentially fitted with a hearing aid in a randomized order with an unvented, a 0.8 mm vented or a 2 mm vented mould and questioned about various aspects of discomfort at the end of each trial period. The three moulds were equally uncomfortable (approximately 17% overall), moist (approximately 34% overall) and associated with an itchy sensation (approximately 36% overall). However, a 0.8 mm and a 2 mm vent significantly reduced the sensation of blockage from 35 to 22% (P less than 0.05) and 13% (P less than 0.001) respectively. A potential disadvantage of venting is feedback, but patients' reports of this can be confused with feedback due to incorrectly inserting the mould. A separate study showed that a 2 mm vent might cause feedback in approximately 10% of patients when used in conjunction with behind-the-ear aids whose maximum gain was 45 dB, but only when the gain was at 42 dB or greater.     

Platinum-based combination chemotherapy for malignant mixed mesodermal tumors of the ovary

Although considerable clinical data are available to guide treatment decisions for patients with ovarian epithelial malignancies, therapy for the rare malignant mixed mesodermal (mullerian) tumor (MMMT) of the ovary is poorly studied. Ten untreated patients diagnosed with primary ovarian MMMT were managed with cis-platinum-based combination chemotherapy from 1980 to 1985. Six of the 10 patients were stage III suboptimal with evaluable residual disease; 4 of these 6 had CRs with a median duration of response of 13 months. The remaining 2 patients had PRs, of 2 and 11 months duration. Four patients had stage III optimal disease; 1 progressed at 7 months, 1 progressed at 16 months and the other 2 patients have no clinical evidence of disease at 12+ and 22+ months. Despite impressive initial response rates, survival overall was poor, with a median survival for all 10 patients of 16+ months.     

Radiotherapeutic alternatives to standard management of adenocarcinoma of the endometrium

Primary radiotherapy as an alternative management for adenocarcinoma of the endometrium was chosen for 117 patients treated at the University of Michigan Medical Center and University of Virginia Medical Center. Cases were selected for radiation because of contraindications to surgery (52.2%) or by protocol for disease outside the endometrium (47.8%). An overall 5-year actuarial survival rate of 49.6% was attained for all stages, with 55% 5-year survival for disease limited to the uterus or cervix. Stage and grade were the most significant risk factors. The addition of external-beam irradiation did not improve local failure rates or survival. Heyman's uterine packing technique was slightly more successful than uterine "line sources" in controlling local disease (P = 0.08). Treatment-related mortality (0.8%) and morbidity (6.8%) were minimal. Surgery, whenever possible, remains the "best standard therapy" but the radiotherapeutic alternative is of significant benefit for those deemed nonsurgical candidates.     

Sentinel node biopsy in vulvar and vaginal melanoma: presentation of six cases and a literature review

Background Urogenital melanoma is a rare neoplasm with poor prognosis. Its management in the past involved radical vulvectomy and complete bilateral inguinofemoral lymphadenectomy. Sentinel lymph node biopsy is an accurate low-morbidity procedure when used in the context of cutaneous melanoma. However, prophylactic lymphadenectomy has not been shown to improve survival of melanoma patients. We wanted to determine the feasibility of sentinel lymph node biopsy in patients with female urogenital melanoma as a staging procedure. Methods Six patients with vulvar or vaginal melanomas underwent preoperative lymphatic mapping with^99mTc-labeled sulfur colloid followed by sentinel lymphadenectomy. In addition, we reviewed the literature on the application of sentinel lymph node biopsy in urogenital tract melanomas. Results One or more sentinel nodes were identified in all six patients by lymphoscintigraphy. All patients underwent sentinel lymphadenectomy, except for one patient with a deep vaginal melanoma that drained to pelvic nodes. The five successful cases had unilateral drainage patterns. None of the sentinel lymph nodes excised had tumor invasion. Combined with five other patients from the published literature, the success rate of localizing sentinel lymph nodes in the patients with urogenital melanoma approaches 100%. Conclusions This experience, plus reports of a small number of patients from three similar studies, supports the impression that sentinel lymph node biopsy is feasible for vulvar and vaginal melanoma.     

Spinal cage retrieval and assessment of biologic response

Implant retrieval programs have been effective in understanding implant failure and biomaterial compatibility in joint arthroplasty; however, its application has not been extended extensively to the assessment of spinal constructs and implants. The objective of this study is to determine the efficacy of implant retrieval analysis as a standard for the assessment of explanted spinal implants. The limitations of clinical radiographic assessment of fusion through metal interbody devices are also identified. The implant analysis protocol is shown through a case report of a titanium mesh spinal fusion cage retrieved from a 54-year-old woman who had a pseudoarthrosis at the T12 cage interface. The implant analysis techniques include backscattered electron imaging, high-resolution contact radiography, histology, and fluorochrome analysis. An implant retrieval analysis program similar to the one discussed in the presented case study will enable an accurate assessment of outcomes of these commonly used implants and will guide future development.     

Challenges of Conducting Community-Based Participatory Research in Boston’s Neighborhoods to Reduce Disparities in Asthma

Boston is one of the preeminent health care and research centers in the world, but for much of its urban core, these resources are largely out of reach. Community Based Participatory Research (CBPR) provides a model with the potential to bridge the gaps between its research prominence and the health of its residents. We report here two case studies of major research projects that were partnerships between universities in Boston and community based organizations and city agencies. The Healthy Public Housing Initiative (HPHI) and the Asthma Center on Community Environment and Social Stress (ACCESS) are projects that provide numerous lessons about the potential and challenges of conducting CBPR. Ensuring that the projects were true partnerships emerged as key issues in both, especially with respect to funding mechanisms and distribution of resources, although the nature of the challenges differed substantially in the two projects. We note that both academic and community partners may harbor stereotypes about the other and that generalizations about broad populations, academics or community members, may not apply well to everyone. Aligning objectives and expectations emerged as another key lesson. In HPHI, tension between service delivery and research was both a source of conflict and a source of creative development that led to divergent but interesting outcomes. In ACCESS, the tensions revolved more around community capacity building while attempting to build and maintain a large cohort for epidemiological investigations. We conclude that open and frank discussion and a transparent process upfront about project direction, finances, expectations, and other dimensions are necessary but not sufficient to address the inherent challenges in CBPR, and that even so, there are likely to be differences in perspective in such partnerships that require honest negotiation throughout the process of the project.