OBJECTIVE:We attempted to evaluate the effect of oral folic acid supplementation on the course of cervical dysplasia.STUDY DESIGN:A total of 235 subjects with grade 1 or 2 cervical intraepithelial neoplasia were randomly assigned to receive either 10 mg of folic acid or a placebo daily for 6 months. Clinical status, human papillomavirus type 16 infection, and blood folate levels were monitored at 2-month intervals. Outcome data were subjected to chi 2 analysis.RESULTS:The prevalence of human papillomavirus type 16 infection initially was 16% among subjects in the upper tertile of red blood cell folate versus 37% in the lower tertile (trend p = 0.035). After 6 months no significant differences were observed between supplemented and unsupplemented subjects regarding dysplasia status, biopsy results, or prevalence of human papillomavirus type 16 infection.CONCLUSION:Folate deficiency may be involved as a cocarcinogen during the initiation of cervical dysplasia, but folic acid supplements do not alter the course of established disease.
A study was undertaken to evaluate the utility of human papillomavirus (HPV) DNA screening and colposcopy in the management of women whose Papanicolaou smears demonstrated atypia less than dysplasia. Fifty patients whose initial Papanicolaou smears were interpreted as showing atypia less than dysplasia were evaluated for the presence of HPV 16 DNA in exfoliated cervicovaginal cells and for histologic findings on biopsy. Those 50 patients were compared to two groups of patients: one consisting of 124 patients with biopsy-documented cervical intraepithelial neoplasia (CIN) and another of 112 patients with normal Papanicolaou smears. The presence of HPV 16 DNA was confirmed with Southern analysis in 46% of patients with atypical Papanicolaou smears, 46% with confirmed CIN and 11.6% with normal Papanicolaou smears. The 50 patients with atypical smears underwent colposcopically directed cervical biopsies, revealing the following results: 14 (28%) had normal histology, 29 (58%) had koilocytosis without dysplasia, and 7 (14%) had CIN. HPV 16 DNA was present in exfoliated cervicovaginal cells from a large percentage of patients from each category (50%) of patients with normal histology, 41.2% with koilocytosis and 57% with CIN). HPV 16 DNA screening did not predict which patients with atypical smears had underlying CIN. Colposcopically directed biopsy remains the evaluation method of choice.
During the past decade there have been remarkable strides in the understanding of the basic mechanism of cancer. It is now clear that there is a set of genes, known as oncogenes, that can cause cells to become malignant if their expression is altered, either by mutation or overexpression. The products of these genes include growth factors, growth factor receptors, signal tranduction proteins, and DNA binding proteins. The normal cellular counterparts of these genes play very important roles in the regulation of growth and proliferation by normal cells. Another set of genes, anti-oncogenes, also play an important role in preventing abnormal cell proliferation. The remarkable explosion of understanding of the pathophysiology of malignancy has led to a common unifying concept of malignant transformation that applies to all tumors. It is likely that these new insights will lead to improved and more specific treatments for malignant disease in the next decade.
DNA isolation and Southern Blot analysis are two of the many techniques currently being used routinely by molecular biologists to discover genetic defects that affect human health. Together these two techniques have greatly aided in the growing knowledge of genetics on a molecular level. Southern blotting can be used to discern genetic deletions, alterations, or amplifications that are not detectable by cytogenetic methods. Several examples of the clinical applications of these methods are discussed in Table 4. Southern analysis has been recently used: (1) to facilitate prenatal diagnosis of sickle cell hemoglobinopathies, (2) to demonstrate human papillomavirus DNA integration in the genome of cervical cancer cells and (3) to demonstrate that oncogene amplification in the tumors of patients with node positive breast cancer correlates inversely with prognosis. Each of these examples not only have diagnostic value for patient care but also may help begin to understand the very basis of the disease processes themselves.
A one-year prospective study of surgeon-specific nosocomial infection rates was done in two community hospitals. Hospital A (93 beds) and Hospital B (158 beds) have nearly identical surgical staffs. Unified criteria for the diagnosis of infections, methods of data collection, and coding were used. Data were processed with an IBM 370 computer using Statistical Analysis System (SAS). Each surgeon received semiannual reports of 1) overall infection rate by site, 2) number of surgical wound infections by wound class and type of procedure, 3) pathogens for each deep and incisional infection, and 4) quarterly wound infection rates by wound class. Analysis of reports revealed high Class I surgical wound infection rates for both general and orthopedic surgeons. One person in each group had inordinately high infection rates. These data serve as an objective incentive to reduce surgical wound infections, identify individual problems, and suggest surgical privileges be evaluated by performance.
A prospective study of surgical wound infections (SWI) in hip prosthesis surgery and total hip and knee replacements at two community hospitals with common surgical staffs was begun in May 1982. The rates of SWI during the first 7 months for four orthopedic surgeons were 9% (3/32) for hip prosthesis surgery and 16.7% (3/18) for total hip and knee replacement, with 12% (6/50) overall. To reduce infections, each orthopedic surgeon agreed to intraoperative surveillance (IOS) of two procedures (hip prosthesis or total hip or knee replacement) by the infection control nurse at each hospital. Significant IOS findings were too many persons in the operating room (five to nine persons), operating room doors opened frequently (25 to 50 times), inconsistent use of prophylactic antibiotics, and excessive conversation. In January 1984, IOS data and recommendations were shared with each orthopedic surgeon, the operating room staff, and the anesthesia personnel. Subsequently, a statistically significant drop in SWI was realized for total hip and knee replacement (1/36 versus 5/36, p = 0.05) and overall (3/73 versus 14/116, p = 0.05). The drop in SWI for hip prosthesis surgery was not statistically significant (2/37 versus 9/80, p greater than 0.10). IOS and individualized communication were effective in reducing SWI.