Clostridium difficile-associated diarrhea: current strategies for diagnosis and therapy

Clostridium difficile, a spore-forming toxigenic bacterium, is one of the most common causes of infectious diarrhea and colitis in the United States. Most patients with C. difficile infection have recently received antimicrobial therapy — usually clindamycin, cephalosporins, or the extended-spectrum penicillins. Clinical presentation varies from asymptomatic colonization to mild diarrhea to severe colitis. The mainstay of diagnosis is detection of C. difficile toxin A, toxin B, or both with a cytotoxin test or enzyme immunoassay of the stool of patients who have received antibiotic therapy and have features of C. difficile-associated diarrhea. Enzyme immunoassays that detect both toxins are preferred because of their higher diagnostic accuracy. If the first assay is negative and C. difficile-associated diarrhea is strongly suspected, a second assay may be performed. Ten days of oral metronidazole is the preferred therapy for most initial infections. Vancomycin is considered secondline therapy because of its cost and potential to select for vancomycin resistance. About 20% to 25% of patients experience reinfection or relapse after initial therapy and require retreatment. The disease can best be prevented by limiting the use of broad-spectrum antibiotics and adhering to control techniques.     

Ultrasound-guided extracorporeal shock wave therapy for plantar fasciitis: a randomized controlled trial

Context  Extracorporeal shock wave therapy (ESWT) is increasingly used for plantar fasciitis, but limited evidence supports its use. Objective  To determine whether ultrasound-guided ESWT reduces pain and improves function in patients with plantar fasciitis. Design  Double-blind, randomized, placebo-controlled trial conducted between April 1999 and June 2001. Setting  Participants were recruited from the community-based referring physicians (primary care physicians, rheumatologists, orthopedic surgeons, and sports physicians) of a radiology group in Melbourne, Australia. Participants  We screened 178 patients and enrolled 166; 160 completed the 15-week protocol. Entry criteria included age at least 18 years with plantar fasciitis, defined as heel pain maximal over the plantar aspect of the foot of at least 6 weeks' duration, and an ultrasound-confirmed lesion, defined as thickening of the origin of the plantar fascia of at least 4 mm, hypoechogenicity, and alterations in the normal fibrillary pattern. Interventions  Patients were randomly assigned to receive either ultrasound-guided ESWT given weekly for 3 weeks to a total dose of at least 1000 mJ/mm² (n = 81), or identical placebo to a total dose of 6.0 mJ/mm² (n = 85). Main Outcome Measures  Overall, morning, and activity pain, measured on a visual analog scale; Maryland Foot Score; walking ability; Short-Form–36 Health Survey (SF-36) score; and Problem Elicitation Technique score, measured at 6 and 12 weeks after treatment completion. Results  At 6 and 12 weeks, there were significant improvements in overall pain in both the active group and placebo group (mean [SD] improvement, 18.1 [30.6] and 19.8 [33.7] at 6 weeks [P = .74 for between-group difference], and 26.3 [34.8] and 25.7 [34.9] at 12 weeks [P = .99], respectively). Similar improvements in both groups were also observed for morning and activity pain, walking ability, Maryland Foot Score, Problem Elicitation Technique, and SF-36. There were no statistically significant differences in the degree of improvement between treatment groups for any measured outcomes. Conclusion  We found no evidence to support a beneficial effect on pain, function, and quality of life of ultrasound-guided ESWT over placebo in patients with ultrasound-proven plantar fasciitis 6 and 12 weeks following treatment.      

Systematic review of diagnostic tests for vaginal trichomoniasis

OBJECTIVE: To review critically and to summarize the evidence of diagnostic tests and culture media for the diagnosis of Trichomonas vaginitis. METHODS: We performed a systematic review of literature indexed in MEDLINE of studies that used Trichomonas culture as the reference standard (9,882 patients, 35 studies). Level I studies (5,047 patients, 13 studies) fulfilled at least two of three criteria: 1) consecutive patients were evaluated prospectively, 2) decision to culture was not influenced by test results, and 3) there was independent and blind comparison to culture. RESULTS: The sensitivity of the polymerase chain reaction technique (PCR) was 95% (95% CI 91% to 99%), and the specificity was 98% (95% CI 96% to 100%). One study was classified as Level I evidence (52 patients). The sensitivity of the enzyme-linked immunosorbent assay was 82% (95% CI 74% to 90%), and the specificity was 73% (95% CI 35% to 100%). The sensitivity of the direct fluorescence antibody was 85% (95% CI 79% to 90%), and the specificity was 99% (95% CI 98% to 100%). Sensitivities of culture media were 95% for Diamond's, 96% for Hollander, and 95% for CPLM. CONCLUSIONS: The sensitivity and specificity of tests to diagnose trichomoniasis vary widely.     

Underascertainment of deaths using social security records: a recommended solution to a little-known problem

Complete and accurate ascertainment of vital status is of great importance in cohort studies. Recently, during the vital status ascertainment phase of an ongoing occupational mortality study, the authors discovered a potentially serious problem with use of the Pension Benefit Information Company's tracing service or any tracing that relies on records from the Social Security Administration (SSA) Death Master File to identify deaths. Their investigation revealed that a number of US states restrict the information in the SSA's Death Master File that is available to researchers and the public as a source of death information. As a result of these findings, the authors recommend a revised two-stage vital status tracing protocol. For stage I, data on all subjects for whom vital status is unconfirmed should be sent to the SSA. For stage II, information on all subjects to whom SSA assigned an unknown vital status as well as all subjects whom SSA identified as known decedents should be submitted to the National Death Index. This new protocol will enable researchers to maximize vital status ascertainment while containing costs associated with death identification.     

DNA macroarray for identification and typing of Staphylococcus aureus isolates

A DNA macroarray containing 465 intragenic amplicons was designed to identify Staphylococcus aureus at the species level and to type S. aureus isolates. The genes selected included those encoding (i) S. aureus-specific proteins, (ii) staphylococcal and enterococcal proteins mediating antibiotic resistance and factors involved in their expression, (iii) putative virulence proteins and factors controlling their expression, and (iv) proteins produced by mobile elements. The macroarray was hybridized with the cellular DNAs of 80 S. aureus clinical isolates that were previously typed by analyses of their antibiograms and SmaI patterns. The set selected contained unrelated, endemic, and outbreak-related isolates belonging to 45 SmaI genotypes. In a gene content dendrogram, the 80 isolates were distributed into 52 clusters. The outbreak-related isolates were linked in the same or a closely related cluster(s). Clustering based on gene content provided a better discrimination than SmaI pattern analysis for the tested mecA(+) isolates that were endemic to Europe. All of the antibiotic resistance genes detected could be correlated with their corresponding phenotypes, except for one isolate which carried a mecA gene without being resistant. The 16 isolates responsible for bone infections were distinguishable from the 12 isolates from uninfected nasal carriers by a significantly higher prevalence of the sdrD gene coding for a putative SD (serine-aspartate) adhesin (in 15 and 7 isolates, respectively). In conclusion, the macroarray designed for this study offers an attractive and rapid typing method which has the advantage of providing additional information concerning the gene content of the isolate of interest.     

Altered metastatic behavior of human breast cancer cells after experimental manipulation of matrix metalloproteinase 8 gene expression

Previous work in our laboratory led to the cloning, from the same parent tumor cell line (MDA-MB-435), of two human breast cancer cell lines (M-4A4 and NM-2C5) with opposite metastatic phenotypes. Additional investigations revealed that the nonmetastatic cell line NM-2C5 overexpressed the neutrophil collagenase, matrix metalloproteinase (MMP)-8, relative to its partner. Because other studies have implicated the MMP family in promoting tumor metastasis, we investigated the apparently paradoxical expression of MMP-8 in these cell lines. By genetic engineering, we inverted its relative levels of expression in the two partners and studied the effects on the behavior of the tumors that they generated in athymic mice. Knock-down of expression in NM-2C5 cells by transduction with a sequence encoding a specific ribozyme and overexpression of MMP-8 in M-4A4 cells by retroviral transduction both strikingly changed metastatic performance in opposite directions, indicating that this gene plays a role in the regulation of tumor metastasis.