Strategies for syphilis prevention: findings from surveys in a high-incidence area.

BACKGROUND: The persistence of syphilis in the United States suggests that a better understanding is needed of the potential for various public health approaches to prevent the spread of the disease. STUDY DESIGN: The authors conducted surveys of 92 persons with early syphilis, 56 uninfected sexual contacts, and 143 neighborhood controls in the Baton Rouge, Louisiana area. The surveys collected information regarding sexual behavior, access to and use of healthcare services, encounters at sites at which serologic screening for syphilis could be done, and exposure to interventions designed to prevent HIV infection. RESULTS: All groups reported high-risk sexual behavior. Cases and contacts were more likely than controls to report two or more sex partners in the previous year, but the three groups were similar in the percentage reporting five or more sex partners. Cases had poor access to health care and by some measures this access was less than that of controls. The potential screening site visited most frequently by cases was the public hospital emergency room (40%). Cases were less likely to have been exposed to programs designed to prevent HIV infection than uninfected contacts and controls combined (odds ratios, 0.51-0.66). CONCLUSIONS: Persons with syphilis were not unlike others in their neighborhoods, suggesting that syphilis is a sentinel event that indicates an entire neighborhood is at risk. Improvements in access to health care for sexually transmitted disease-related symptoms, screening in sites such as public hospital emergency rooms, and emphasizing sexual risk-reduction interventions may limit the spread of syphilis in these neighborhoods. To prevent syphilis in the long term, public health programs should also try to better understand and change other community-level socioeconomic factors that influence sexual behavior.

Potential for community-based screening, treatment, and antibiotic prophylaxis for syphilis prevention.

BACKGROUND: The recent syphilis epidemic in Louisiana occurred predominantly among disadvantaged African Americans who may distrust public health agencies and prevention efforts. OBJECTIVES: To determine community perceptions regarding trust and use of public health clinics, to assess whether race of provider is important to persons at risk for syphilis, and to assess the willingness of persons to participate in syphilis screening, treatment, and antibiotic prophylaxis. STUDY DESIGN: Qualitative interviews were conducted with 18 community leaders and 38 community members who were at risk for syphilis. Quantitative surveys were completed by persons with primary or secondary syphilis (n = 92), their sexual contacts (n = 56), and with neighborhood controls (n = 143). Three possible programs for syphilis screening and antibiotic prophylaxis were proposed (1) bar setting; (2) home setting, and (3) mobile health-van setting in high-risk communities. RESULTS: In qualitative interviews, community leaders and community members reported a high degree of trust in the public sexually transmitted disease clinic. A majority of respondents felt that race was not a factor in choosing healthcare providers. Respondents favored the provision of services in a mobile health van over in a bar or in their homes. In quantitative interviews, more than 80% of community members surveyed reported that they would go to a mobile health van for syphilis testing. Nearly two thirds of respondents reported that they would be willing to take oral prophylaxis for syphilis, and more than half of respondents reported that they would accept an injection. CONCLUSIONS: Community members trust the public sexually transmitted disease (STD) clinic, are generally not concerned with the race of healthcare providers, and are supportive of community-based STD screening, treatment, and antibiotic prophylaxis provided from a mobile clinic.

Emerging lessons of the Interdisciplinary Generalist Curriculum (IGC) Project.

The Interdisciplinary Generalist Curriculum Project (IGC) was funded in 1993 by the Health Resources and Services Administration with the goal of developing innovative preclinical generalist curricula in ten of the nation's medical and osteopathic schools. The IGC successfully completed two competitive cycles in which ten schools were awarded three-year contracts. Although the long-term goal of the project is to increase the proportion of medical students choosing generalist careers, much has been learned thus far about the processes of curricular change and interdisciplinary cooperation. Drawing on information from school reports, site visits, external evaluations, academic presentations, and annual project meetings, this report presents the emerging lessons learned in the key areas of interdisciplinary collaboration, recruitment and retention of community preceptors, faculty development, and integration of generalist-related components into the four-year medical school curriculum. These lessons should prove useful for other schools embarking upon significant curricular innovations.

The interdisciplinary generalist curriculum project: a national medical school demonstration project.

The United States is facing the challenge of producing more generalists for the physician workforce. The Primary Care Organizations' Consortium (PCOC) has responded by focusing on how medical education can be modified to enhance and support medical students' interest in and commitment to generalism early in their training. Evolving from PCOC's developmental work, the five-year Interdisciplinary Generalist Curriculum (IGC) Project was developed to encourage the nation's schools of medicine and colleges of osteopathic medicine to implement interdisciplinary generalist curricula in the preclinical years. Funded by the Division of Medicine in the Bureau of Health Professions of the Health Resources and Services Administration (HRSA), the IGC Project has successfully developed and implemented a nationally competitive medical school demonstration project. Thirty-three schools submitted proposals for an IGC Project award; nine were selected for site visits, from which five were chosen to receive three-year awards. Rigorous attention to creating and maintaining an interdisciplinary focus has characterized the first phase of the IGC Project. Shared leadership among the Executive Committee's project director and two project codirectors and parity in representation among the three disciplines of family medicine, internal medicine, and pediatrics on the Advisory Committee have formed a critical foundation for interdisciplinary functioning within the project. Growing national interest in generalist training and other funding initiatives have contributed to acceptance of the IGC Project. The high level of interest in the IGC Project and the successful interdisciplinary collaboration during the first phase would indicate that the interdisciplinary process can be replicated to move the nation's medical education institutions toward the production of needed generalist physicians.

Instability of the cervical spine after decompression in patients who have Arnold-Chiari malformation.

Stability of the cervical spine was studied in two groups of children who had myelomeningocele. Group I consisted of twenty children who had an Arnold-Chiari Type-II malformation in whom a suboccipital craniectomy (partial occipital craniectomy through the suboccipital route) and cervical laminectomy was done to decompress the brain stem. The average duration of follow-up in this group (excluding one patient) was 4.7 years (range, 2.3 to 10.4 years) after the operation. Group II consisted of twenty children who had myelomeningocele but had not had an operation for decompression. Lateral radiographs of the cervical spine in flexion and extension showed no instability between the occiput and atlas or between the atlas and axis in either group. In contrast, translation between the second and third cervical vertebrae averaged four millimeters in Group I and one millimeter in Group II (p less than 0.01), and angulation between the third and fourth cervical vertebrae averaged 17 degrees in Group I and 6 degrees in Group II (p less than 0.01). Nineteen of the twenty patients in whom a suboccipital craniectomy and cervical laminectomy (Group I) had been done had instability of the cervical spine.

Platelet reactivity in vivo in dogs with arterial prostheses seeded with endothelial cells.

This study was designed to assess platelet activity in vivo with vascular prostheses seeded with endothelial cells to determine the time course for development of thromboresistance and to test the ability of prostheses to produce prostacyclin. Sixteen dogs were randomly allocated to receive seeded (experimental group) or unseeded (control group) velour Dacron aortic prostheses. Serial measurements of platelet survival were performed to assess platelet interaction with prostheses in vivo, and platelet serotonin was monitored as an index of platelet release in vivo. After placement of prostheses, dogs in the experimental group had rapid normalization of platelet survival, with most having normal platelet survival at 4 to 8 weeks after surgery. In contrast, most control animals had reduced platelet survival throughout the 12 week period of study. Significant differences between groups in mean platelet survival were noted at 8 weeks after surgery (p less than .005) and in mean platelet serotonin at 12 weeks after surgery (p less than .05). Luminal surface production of 6-keto-PGF1 alpha from seeded prostheses was similar to aortic production and significantly greater (p less than .05) than that of control prostheses. Gross thrombus was present on 6.0 +/- 3.4% of the prosthetic surface in experimental animals in comparison to 26.6 +/- 19.2% in controls (p less than .005). The results of these studies document accelerated nonreactivity with platelets of seeded prostheses due to rapid coverage with endothelium possessing a normal ability to produce prostacyclin.

Enhanced patency of small-diameter, externally supported Dacron iliofemoral grafts seeded with endothelial cells.

Fourteen adult foxhounds underwent bilateral iliofemoral bypasses with externally supported, knitted Dacron grafts measured 4 mm in internal diameter and 10 cm in length. These conduits were preclotted with 10 ml of blood mixed with 0.5 ml of culture medium. Autologous endothelial cells, enzymatically derived from external jugular veins, were added to blood and medium used to preclot one graft in each dog. The other, unseeded graft served as a control. Grafts were anastomosed, end to end, to the iliac and femoral arteries. All dogs received dipyridamole, 50 mg twice a day for 4 days preoperatively, and aspirin, 5 grains four times a day for 1 day preoperatively. Both drugs were continued 14 days after operation. Grafts were removed from three dogs at 2 and 4 weeks and from four dogs at 8 and 16 weeks. All grafts were patent at 2 weeks during drug administration. Cumulative patency rates beyond 2 weeks were 73% in 11 seeded grafts and 27% in 11 control grafts, a statistically significant difference (P = 0.03). Seeded grafts were completely surfaced with a monolayer of endothelium between 2 and 4 weeks. Small-graft patency appeared related to evolution of endothelial surfaces, the development of which was clearly facilitated by seeding with autologous endothelium.

Expanded polytetrafluoroethylene vascular prostheses seeded with enzymatically derived and cultured canine endothelial cells.

Thirteen adult dogs underwent thoracoabdominal bypass operations with 6 or 10 mm expanded polytetrafluoroethylene (PTFE) grafts 25 to 30 cm long. Eight experimental grafts were seeded with cultured autologous endothelial cells prior to implantation. Five unseeded grafts served as controls. Endothelial cells, derived from external jugular vein segments using 0.1% trypsin and 0.5% collagenase solutions, were cultivated for 14 days prior to seeding. Grafts were studied at 2 and 4 weeks after implantation. Endothelial linings in control grafts were restricted to limited anastomotic pannus ingrowths, never exceeding 10% of the graft surface. Experimental grafts demonstrated an endothelial surface coverage averaging 64% and 91% at 2 and 4 weeks, respectively. Generation of an early lining of endothelium in expanded PTFE grafts is possible in a canine model using cultured autologous cells.

Isolation of adult canine venous endothelium for tissue culture.

In order to provide autologous adult endothelial cells for the production of cell-lined artificial vascular prostheses, we have developed a method for harvesting large numbers of cells with minimal contamination by other cellular types. In this technique, the vein is incubated in trypsin-EDTA solution followed by collagenase and the endothelial cells flushed off with a stream of culture medium. With care and appropriate timing, the endothelium can be selectively removed leaving the underlying basal lamina intact.

Immediate seeding of enzymatically derived endothelium in Dacron vascular grafts. Early experimental studies with autologous canine cells.

Twenty-eight adult dogs underwent thoracoabdominal bypass with 6-mm double-velour Dacron grafts. The experimental grafts were seeded immediately prior to implantation with enzymatically harvested endothelial cells. Endothelial cells were procured from autologous external jugular vein segments using 0.1% trypsin and 0.5% collagenase solutions. Unseeded grafts served as controls. The grafts were studied from one to 28 days after implantation. The seeded grafts exhibited greater than 80% uniform luminal coverage with endothelial cells at day 28. Immunofluorescent microscopy was used to confirm the presence of endothelium. The experimental grafts studied at the two time periods of one to seven days and 14 to 28 days had 94.6% and 88.5% clot-free surfaces, respectively. The control grafts studied during similar periods had 81.0% and 40.1% clot-free surfaces. These differences were significant at the 14- to 28-day period.

Endothelial cell seeding of prosthetic vascular grafts: early experimental studies with cultured autologous canine endothelium.

Thirteen adult dogs underwent thoracoabdominal bypass operations with 6-mm, double-velour Dacron grafts 25 to 30 cm long. Experimental grafts were seeded with cultured autologous endothelial cells (n = 7). Unseeded grafts served as controls (n = 6). Endothelial cells were harvested from external jugular vein segments using 0.1% trypsin and 0.5% collagenase solutions. Grafts were studied at weeks 2 and 4. Endothelial cell coverage of experimental graft surfaces after two weeks was 60% to 70%, and approximately 80% after four weeks. Immunofluorescence using factor VIII-related antigen confirmed the graft's inner surface to be endothelium. Endothelial cell coverage in control grafts occurred as pannus ingrowth, and never exceeded more than 10% of the conduit surface. Generation of an early endothelial surface in prosthetic grafts is possible in a canine model using cultured autologous cells.

Adult rat lung in organ culture: maintenance of histotypic structure and ability to synthesize phospholipid.

The maintenance of adult rat lung explants in organ culture was assessed both morphologically and biochemically. A comparison of several culture media indicated that Ham's F12K plus 1.0 microM dexamethasone, which maintained the explants for 14 days, was superior. The ability of the explants to synthesize dipalmitoylphosphatidylcholine increased with the length of cultivation to values greater than the noncultivated controls. The DNA content remained constant for 7 days, and a relatively normal structural relationship between type I and type II pneumocytes was maintained. Explants cultivated in Ham's F12K without dexamethasone did not maintain a histotypic morphology; the type II pneumocytes appeared to proliferate and the ability to synthesize phosphatidylcholine decreased.

Effect of vitamin A and methylprednisolone on canine prostate in organ culture.

Organ explants from the canine prostate with and without methylprednisolone pretreatment were cultivated for ten days in Trowell's T-8 medium or medium supplemented with testosterone and/or vitamin A. Upon termination of the experiments, explants were fixed and examined histologically. All glands from the most central section of each explant were graded according to epithelial type, and from these grades the proportion of acini with maintained columnar cells was calculated for each explant. Stromal cellular maintenance was also estimated. While a small proportion of explants from the vitamin-treated and methylprednisolone-pretreated groups showed epithelial maintenance, a combination of these treatments significantly increased such maintenance. Stromal maintenance was enhanced with methylprednisolone pretreatment but not by vitamin A. These results are in accord with the hypothesis that methylprednisolone acts to stabilize the lysosomal membrane, thus protecting tissue against the effects of ischemic shock. In protected explants vitamin A is able to maintain a columnar glandular epithelium. In a subsequent experiment a series of linoleic acid dosages was tested in the presence or absence of vitamin A. In neither case was this fatty acid of value in improving epithelial or stromal maintenance.

Organ culture of canine prostate.

The simple life support system of organ culture contrasts sharply with the life support system in vivo. Organ culture, a technique for characterizing the effect of various substances on an organ, has potential clinical usefulness in many areas. In the present case explants of canine prostate are minimally maintained when cultivated in a medium enriched with testosterone and insulin. Pretreatment of the dog with methylprednisolone or the addition of vitamin A markedly improves the maintenance of normal structure. Methylprednisolone pretreatment and the addition of vitamin A had a significant synergistic effect. The clinical significance and implications of the findings are presented. We believe these preliminary experiments with organ culture can serve as a basis for deciphering some of the complex functions or an organ.

Effect of testosterone on long-term organ cultures of canine prostate.

Organ cultures of rodent and human prostate glands have shown marked differences in their morphological response to testosterone. In this study, explants from 19 canine prostate glands were cultivated for a minimum of 9 days in Trowell's T-8 medium. Groups of explants were exposed to media containing from 0.05 to 100 mum testosterone. While the higher testosterone levels (50 and 100 mum) markedly decreased explant viability, explants cultivated at lower levels (0.05 to 5 mum) appeared similar to control explants in testosterone-free Trowell's T-8 medium. Atmospheric mixtures containing either 95% or 50% oxygen were equally effective. Shortly after the cultures were initiated, large amounts of secretory product were liberated into the lumen. After 9 or more days in vitro, glandular epithelium appeared cuboidal and never revealed the acid phosphatase-rich secretory granules seen in the preculture control. However, the epithelium exhibited an increase in alkaline phosphatase and lipid content following cultivation.