Evaluating the quality of clinical practice guidelines.

OBJECTIVE: To review and identify established methods for evaluating the quality of practice guidelines and to use a selected assessment tool to assess 2 chiropractic practice guideline documents. METHODS: A search of the medical literature was performed to identify current methods and procedures for practice guideline evaluation. Two chiropractic practice guideline documents, Vertebral Subluxation in Chiropractic Practice (CCP) and Guidelines for Chiropractic Quality Assurance and Practice Parameters (Mercy) were then independently evaluated for validity by 10 appraisers using the identified appraisal tool. The appraisal scores were tabulated, and consensus appraisals were generated for the CCP and Mercy guideline documents. RESULTS: The "Appraisal Instrument for Clinical Guidelines" (Cluzeau instrument) was identified as a reliable and valid method of guideline evaluation. The result of the application of this appraisal tool in the assessment of the CCP and Mercy guideline documents was that the former scored notably lower than the latter. On the basis of the results of the guideline appraisals, the CCP document is not recommended, and its guidelines are not considered suitable for application in chiropractic practice. The Mercy guidelines are recommended for application in chiropractic practice, with the proviso that new scientific data should be considered. CONCLUSIONS: The literature reviewed suggests that professional organizations or groups should undertake a critical review of guidelines using available critical guideline appraisal tools. Guideline validity appraisal should be done before acceptance by the chiropractic profession. To avoid unwarranted utilization of poorly constructed guidelines, it is strongly recommended that all future guidelines be reviewed for validity and scientific accuracy with the findings published in a medically indexed journal before they are adopted by the chiropractic community.

Overview of DOD activities in ecological risk assessment.

Under the Comprehensive Environmental Response, Compensation and Liability Act, Congress has mandated that all designated hazardous waste sites will be remediated to protect human health and the environment. This law is the driving force behind the Department of Defense (DOD) ecological risk assessment (ERA) program. Ecological risk assessments are currently underway at many DOD sites with budgets ranging from five thousand to ten million dollars. However, with the advent of downsizing government and shrinking funds, efforts are being made within DOD to better refine these assessments. Two DOD work groups function to develop guidance for and assist project managers with the ERA process. These groups are the Army Biological Technical Assistance Group chaired by the Army Environmental Center and the Tri-Service Ecological Risk Assessment Work Group (ERWG) chartered by the Tri-Service Environmental Support Centers Coordinating Committee. Membership in the Tri-Service ERWG includes all facets of DOD. In the research arena, the Fate & Effects Research and Development Program is one of four primary thrust areas under the Army's Environmental Quality Technology Program "Clean Up" pillar. This program is currently being executed by three laboratories, the Waterways Experiment Station, Vicksburg, MS, the Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, MD, and the Army Center for Environmental Health Research (Provisional), Ft. Detrick, MD. The goal of this program is to provide tools to improve environmental risk assessments, both human and ecological. The research is geared toward addressing user requirements and is defined by the Fate and Effects Research Program.

Molecular markers of ionizing radiation-induced gene mutations in mammalian cells.

We have isolated independent Chinese hamster ovary (CHO) cell mutants at the hypoxanthine guanine phosphoribosyltransferase (hprt) locus from untreated, 60Co gamma-ray-exposed, and 212Bi alpha-exposed cells and identified the molecular changes underlying the mutation determined by multiplex polymerase chain reaction (PCR)-based exon deletion analysis. Both the parental CHO-K1 cells and the X-ray-sensitive mutant xrs-5 cells were studied. The radiosensitive xrs-5 cells are defective in DNA double-strand break rejoining ability and in V(D)J recombination, which can be complemented by Ku protein. Of the 71 spontaneous CHO-K1 hprt mutants analyzed, 78% showed no change in exon number or size, 20% showed loss of one to eight exons (partial deletion), and 3% showed loss of all nine hprt exons (total deletion). Exposure of CHO-K1 cells to 6 Gy of gamma rays, which reduced survival levels to 10%, produced a high deletion spectrum with 45% of the 20 mutants analyzed showing a loss of one to eight exons and 30% showing total deletion. Exposure to an equitoxic dose of alpha radiation from 212Bi, a 220Rn daughter, resulted in a spectrum similar to the gamma-ray spectrum in that 75% of the 49 mutants analyzed were deletions. To alpha radiation, however, tended to produce larger intragenic deletions than gamma radiation. Of the 92 spontaneous xrs-5 mutants analyzed for deletions, 43% showed a loss of one to eight exons and 14% showed total deletion. This suggests that, in certain regions of the hprt gene, base alterations can be converted into large deletions and alteration in the Ku protein complex can influence this type of mutational process. Exposure to alpha radiation (10% survival) to xrs-5 cells resulted in a deletion spectrum similar to that seen in CHO-K1 cells. Of the 49 mutants analyzed, 43% showed on change in exon number or size, 16% showed a loss of one to eight exons, and 41% showed total deletion. While the defect in xrs-5 cells has a profound effect on spontaneous mutant spectra, this defect does not appear to affect alpha-induced mutation spectra.

The molecular nature of spontaneous mutations at the hprt locus in the radiosensitive CHO mutant xrs-5.

The radiosensitive mutant xrs-5, a derivative of the Chinese hamster ovary (CHO) K1 cell, is defective in DNA double-strand break rejoining ability and in V(D)J recombination. The radiosensitivity and defective repair phenotype are complemented by the 80-kDa subunit of the Ku protein. We determined the nature of the mutations that develop spontaneously at the hprt locus in this cell line using both multiplex PCR deletion screening and DNA sequencing. Ninety-two independent spontaneous mutants were analyzed and the results were compared to the mutation spectrum of 64 previously analyzed hprt spontaneous mutants isolated from the parental CHO-K1 cell line. More than 50% of the spontaneous xrs-5 mutants had lost one or more exons while less than 25% of spontaneous CHO-K1 mutants had lost one or more exons. Most of the deletions in xrs-5 cells involved the loss of multiple exons while single exon deletions predominated in CHO-K1. There was also a nonrandom distribution of breakpoints in both CHO-K1 and xrs-5. Most of the deletion breakpoints were 3' to exon 9, around exons 4-6, or near exon 1. Although the frequency of base substitutions was lower in xrs-5, the spectrum of base substitutions was qualitatively similar to that of CHO-K1. There was no significant difference in the spontaneous mutant frequency in xrs-5 and CHO-K1. The results suggest that in certain regions of the hprt gene, base alterations can be converted to large deletions, and that alterations in the Ku protein complex can influence this process.

The isolation of sucrose-fermenting Salmonella mbandaka.

During media trials to evaluate the use of Brilliant Green Agar for the primary recognition of Salmonella, strains presenting fermentation reactions were observed. All fermenting strains (84 out of 145) belonged to the serotype Salmonella mbandaka (58%), and the activity was expressed on three batches of Brilliant Green Agar and one of Xylose-Lysine Desoxycholate Agar. It was established using individual lactose and sucrose broth that the reaction in these media was due to sucrose fermentation. The most frequently isolated Salmonella in this laboratory during 1990 was S. mbandaka (61%) i.e. 65 of the 106 isolates during this period. Primary differentiation of Salmonella from other members of the family Enterobacteriaceae on media incorporating sucrose would have resulted in 36% of Salmonella isolates not being recognised. BGA and XLD agar therefore would not be suitable for primary isolation of Salmonella from clinical material with such a high percentage of the major isolate, S. mbandaka, having the ability to ferment sucrose.

Utilization review of the use of BACTEC PLUS high-volume blood culture bottles.

The BACTEC PLUS 26 (NR26) (Becton Dickinson, Towson, Md.) high-volume blood culture bottle replaced the less expensive smaller-volume NR6A bottle in our hospital. An audit carried out several months after their introduction revealed that only 17.5% of the NR26 bottles received the required blood volume. Several audits and educational programs were required in order to achieve a compliance rate of > 60%.

Types of Salmonella paratyphi B and their phylogenetic significance.

The substrates inositol, rhamnose, d-tartrate and m-tartrate used in fermentation tests with 338 cultures of Salmonella paratyphi B differentiated strains in some phage types to give information that could be used in epidemiological investigations. Xylose in Bitter's medium, the fifth substrate by which 13 of a potential 32 biotypes were identified, differentiated few cultures with the negative character. The possession of a specific type of outer-membrane protein receptor for colicin M or bacteriophage ES18 and the particular type of ribosomal ribonucleic acid present, defined three groups among the phage-typed and biotyped cultures. The possibility that the serotype S. paratyphi B contains clones of different phylogenetic origin and the consequent implications for nomenclature are discussed.