Are genes encoding proteoglycans really associated with the risk of anterior cruciate ligament rupture?

Proteoglycans are considered integral structural components of tendon and ligament and have been implicated in the resistance of compressive forces, collagen fibrillogenesis, matrix remodelling and cell signalling. Several sequence variants within genes encoding proteoglycans were recently implicated in modulating anterior cruciate ligament ruptures (ACLR). This study aimed to test the previously implicated variants in proteoglycan and vascular epithelial growth factor encoding genes with risk of ACLR in a population from Poland. A case control genetic association study was conducted using DNA samples from 143 healthy participants without a history of ACL injuries (99 male and 44 females) (CON group) and 229 surgically diagnosed ACLR participants (158 males and 71 females). All samples were genotyped for the ACAN: rs1516797, BGN: rs1042103, rs1126499, DCN: rs516115 and VEGFA: rs699947 variants. Main findings included the (i) ACAN rs1516797 G/T genotype which was underrepresented in the CON group (CON: 36%, n=52, ACLR: 49%, n=112, p=0.017, OR=1.68, 95% CI 1.09 to 2.57) when all participants were investigated and (ii) the BGN rs1042103 A allele was significantly under-represented in the male CON group compared to the male ACLR group (CON: 39%, n=78, ACLR: 49%, n=156, p=0.029, OR=1.5, 95% CI 1.05 to 2.15). Furthermore, BGN inferred haplotypes were highlighted with altered ACLR susceptibility. Although the study implicated the ACAN and BGN genes (combination of genotype, allele and haplotype) in modulating ACLR susceptibility, several differences were noted with previous published findings.

Role of anterior temporal cortex in auditory sentence comprehension: an fMRI study.

Recent neuropsychological and functional imaging evidence has suggested a role for anterior temporal cortex in sentence-level comprehension. We explored this hypothesis using event-related fMRI. Subjects were scanned while they listened to either a sequence of environmental sounds describing an event or a corresponding sentence matched as closely as possible in meaning. Both types of stimuli required subjects to integrate auditory information over time to derive a similar meaning, but differ in the processing mechanisms leading to the integration of that information, with speech input requiring syntactic mechanisms and environmental sounds utilizing non-linguistic mechanisms. Consistent with recent claims, sentences produced greater activation than environmental sounds in anterior superior temporal lobe bilaterally. A similar speech > sound activation pattern was noted also in posterior superior temporal regions in the left. Envirornmental sounds produced greater activation than sentences in right inferior frontal gyrus. The results provide support for the view that anterior temporal cortex plays an important role in sentence-level comprehension.

Stability of a second-generation cephalosporin veterinary mastitis formulation after electron beam irradiation.

This study focused on the chemical stability of the cephalosporin (6R, 7R)-7-(1-pentafluorophenoxyacetamido)-3-[2-(5-methyl-1,3,4-thiodiazolyl)thiomethyl]-Delta(3)-cephem-4-carboxylic acid, sodium salt (cephem 1) formulation after electron beam (e-beam) irradiation. The cephem 1 concentrations of samples irradiated at 5, 10, and 15 kilograys for glass vials and low-density polyethylene (LDPE) cannula syringes were not statistically different from the concentrations of the nonirradiated control samples. Samples from each irradiation dose stored in controlled-temperature chambers at 5 degrees C and 30 degrees C for 24 months did not show any concentration changes within statistical limits compared with the nontreated samples. Samples from each irradiation dose stored at 40 degrees C for 12 months also did not show any concentration changes within statistical limits compared with the nontreated samples. The percentage of related substances increased slightly with the increase in e-beam irradiation level and storage temperature, but this increase was within the proposed label claim of 90% to 110% (45-55 mg/g). In conclusion, e-beam sterilization did not affect the chemical stability of cephem 1 intramammary formulation in LDPE cannula syringes, suggesting that e-beam irradiation may be a feasible method for terminal sterilization of this cephem 1 formulation.

Distress, personality, and mammography utilization among women with a family history of breast cancer.

The authors examined the impact of psychological distress and the personality construct of conscientiousness (as measured by the Neuroticism, Extraversion, and Openness-Five Factor Inventory) on mammography utilization among women who were at increased risk for breast cancer. Participants were 200 women who had at least 1 first degree relative with breast cancer. Overall, 80% of the participants had obtained a mammogram in the previous year. Analyses controlling for potential confounders (perceived risk, decisional balance, and physician recommendation for mammography), revealed that distress was negatively associated with mammography utilization among participants who were low in conscientiousness. Distress was not significantly related to mammography utilization among highly conscientious women. The results are discussed in terms of their implications regarding interventions designed to increase mammography utilization in this population.

Acquisition of Clostridium difficile and Clostridium difficile-associated diarrhea in hospitalized patients receiving tube feeding.

BACKGROUND: Clostridium difficile is the most common infectious cause of nosocomial diarrhea, but its role in diarrhea associated with tube feeding has not been rigorously investigated. OBJECTIVE: To determine the incidence of C. difficile acquisition and C. difficile-associated diarrhea in tube-fed and non-tube-fed patients. DESIGN: Prospective cohort study. SETTING: A university-affiliated Veterans Affairs Medical Center. PATIENTS: 76 consecutive hospitalized, tube-fed patients and 76 hospitalized, non-tube-fed patients. The two cohorts were matched for age, unit location, duration of hospitalization before surveillance, and severity of illness. MEASUREMENTS: Incidence of C. difficile acquisition, incidence of C. difficile-associated diarrhea, and C. difficile restriction endonuclease analysis typing results. RESULTS: More tube-fed patients than non-tube-fed patients acquired C. difficile (15 of 76 patients [20%] compared with 6 of 76 patients [8%]; P=0.03) and developed C. difficile-associated diarrhea (7 of 76 patients [9%] compared with 1 of 76 patients [1%]; P=0.03). The mean proportion (+/-SD) of surveillance days with diarrhea was greater for tube-fed patients after the development of C. difficile-associated diarrhea than for tube-fed patients without this diarrhea (0.68+/-0.4 compared with 0.22+/-0.2 [95% CI for the mean difference, 0.08 to 0.84]). Postpyloric tube feeding (odds ratio, 3.14 [CI, 1.008 to 9.77]) and duration of surveillance (odds ratio, 1.08 [CI, 1.0009 to 1.16]) were risk factors for the acquisition of C. difficile. Nineteen restriction endonuclease analysis types of C. difficile were identified from 20 patients. CONCLUSIONS: Hospitalized, tube-fed patients, especially those receiving postpyloric tube feeding, are at greater risk for the acquisition of C. difficile and the development of C. difficile-associated diarrhea than are hospitalized, non-tube-fed patients. Clinicians should test for C. difficile in tube-fed patients with diarrhea.

Ambiguity in the identification of Streptococcus pneumoniae. Optochin, bile solubility, quellung, and the AccuProbe DNA probe tests.

We prospectively evaluated 639 sequential clinical isolates of alpha-hemolytic gram-positive cocci as possible Streptococcus pneumoniae. On the basis of results of tests for optochin susceptibility, tube bile solubility, and the quellung reaction, 74 strains (11.6%) were categorized as unequivocal pneumococci (optochin positive, tube bile solubility positive, quellung reaction positive). Among 450 optochin- and tube bile solubility-negative organisms, a subset of 56 strains was tested for quellung reaction (all negative); these isolates were categorized as unequivocal nonpneumococci. A final 115 organisms with an inconsistent or discordant combination of susceptibility to optochin, tube bile solubility, and quellung reaction were categorized as equivocal strains. With the unequivocal isolates, a commercial molecular probe for S pneumoniae (AccuProbe; Gen-Probe, San Diego, Calif) showed 100% sensitivity (74/74) and 100% specificity (56/56). Among the 115 equivocal strains, however, 33 (28.7%) reacted with the AccuProbe, whereas only 3 (2.6%) showed a capsule that reacted in the quellung test. A subset of the equivocal strains identified in this group of primarily respiratory isolates may have been S pneumoniae that only partially expressed their classic phenotype of optochin susceptibility and bile solubility and only rarely expressed capsular antigens. A practical, cost-sparing algorithm is proposed to facilitate the routine clinical identification of S pneumoniae.

Radical improvements in the display of clinical microbiology results: a Web-based clinical information system.

OBJECTIVE: To evaluate the performance of a novel computerized system for reporting clinical microbiology results. The new system provides a summarized overview of a patient's current (or past) microbiological status, with the option to selectively explore in greater depth. It is deployed using World Wide Web technology, which supports virtually any kind of computer and allows physicians to obtain results via the internet using personal computers in the office or at home. METHODS: In an unblinded crossover study at a university-affiliated medical center, participants used both the new system and a conventional display system to retrieve selected microbiology results for two actual patients, according to standardized questionnaires, with balanced allocation of sequence of system use. Participants also subjectively rated the two systems. The participants were 16 physician, pharmacist, and nurse volunteers. Outcome measures included completion time and number of errors (categorized as major and minor) associated with results retrieval, and participants' ratings of the new system. RESULTS: Mean completion time was 45% shorter (13.9 versus 25.5 minutes; P < 0.001), and there were fewer associated major errors (0 versus 13; P = 0.01) and minor errors (10 versus 21; P = 0.003) with the summarized display system. All participants rated the new system as easier to learn and use than the conventional system. CONCLUSIONS: A system that appropriately summarizes and groups microbiology results can significantly shorten retrieval times and reduce interpretive errors, while providing users with information needed for cost-effective therapy. Such a system can be deployed by leveraging the rapidly evolving technology of the World Wide Web.

Closing the clinical laboratory testing loop with information technology.

Information technology can enhance the effectiveness of the part of the laboratory testing loop that occurs outside of the clinical laboratory. That external component involves the presentation of laboratory results and related information to physicians and the reception of physician requests for follow-up testing. Improvements made in the clinician-computer interface can conceivably enhance the quality of information transfer of this part of the testing loop and thereby improve the effectiveness of the entire loop. Our experience has been that results presentation is easier to address than order reception and that the economic benefits from improved result presentation can be substantial. Improving order reception requires more finesse, especially with the limitations of today's health systems and their information systems in mind. For instance, effective computer-based management of prospectively developed orders (eg, clinical protocols) not only can have a substantial positive impact on test use, but is actually welcomed by clinicians. Application of information technology at the clinician-computer interface has good potential to foster more appropriate use of clinical laboratory resources.

The clinical workstation as a means of improving laboratory use.

Driven to make timely decisions, doctors may act with less than all of the relevant patient data. Sub-optimal use of clinical laboratory resources can result. Our clinicians' workstation (CWS) is meant to provide doctors and nurses ready access to laboratory results in a form that makes the data easy to review and use. In addition, the workstation provides immediate feedback regarding blood orders, to encourage appropriate clinical practice. Feedback is based on the medical staff's clinical guidelines that have been incorporated into an embedded expert system. CWS also helps blood bank physicians to monitor, review and control requests for special needs such as irradiated products. Challenges to system acceptance await those trying to bring functional decision support to the clinical environment. Among these are barriers to understanding and cooperation posed by departmental boundaries and interacting professional cultures as well as the politics of hospital-based information systems.

A clinician's workstation for improving laboratory use. Integrated display of laboratory results.

Physicians are often forced to make decisions about the use of laboratory resources without adequate access to earlier results and related supporting information. Less than optimal use of the laboratory may result. The authors developed and deployed a clinical workstation meant to provide ready access to laboratory information that is presented in a format well-matched to the patient monitoring task. The workstation was one element of a multifaceted effort to improve blood component use in adult and pediatric bone marrow transplantation units. It was the sole intervention focused on improving laboratory testing. In the 2 years since the introduction of the workstation, median charges of bone marrow transplantation cases for laboratory test fell by 32%. This reduction in charges has been maintained for 2 years. Better informed physicians appear to use laboratory resources more sparingly.

User interface reengineering. Innovative applications of bar coding in a clinical microbiology laboratory.

Some clinical laboratory departments (such as microbiology) provide extensive reporting of text and other data not generated by instruments that can be interfaced to a laboratory information system. These data are usually entered into the laboratory information system manually by keyboard data entry, which can be cumbersome and time consuming. Bar codes, which are already used in laboratories to facilitate rapid entry of sample-identifying information, have the potential to be used much more broadly as a generalizable data entry technique. We developed a comprehensive system that takes advantage of several applications of bar coding to facilitate the work of our Clinical Microbiology Laboratory. Central to our system is the use of bar code "scripts" to meet many of our complex data entry requirements. Use of these scripts is transparent to the laboratory information system (ie, no special "drivers" are needed) because data are received as if they had been generated by typing the characters on the keyboard. The scripts consist of bar codes that encode the series of keystrokes needed to give the appropriate response at the series of prompts offered by the laboratory information system. Both alphanumeric and other keys, including carriage returns and special characters, can be converted into bar codes and incorporated into scripts. By creating and printing these scripts in the laboratory using standard wordprocessing software and bar code fonts for personal computers, laboratorians without specialized computer training have the tools to substantially improve the data entry efficiency of existing data entry terminals for a variety of laboratory information systems.

Integrating legacy laboratory information systems into a client-server world: the University of Minnesota Clinical Workstation (CWS) project.

The development of an innovative clinical decision-support project such as the University of Minnesota's Clinical Workstation initiative mandates the use of modern client-server network architectures. Preexisting conventional laboratory information systems (LIS) cannot be quickly replaced with client-server equivalents because of the cost and relative unavailability of such systems. Thus, embedding strategies that effectively integrate legacy information systems are needed. Our strategy led to the adoption of a multi-layered connection architecture that provides a data feed from our existing LIS to a new network-based relational database management system. By careful design, we maximize the use of open standards in our layered connection structure to provide data, requisition, or event messaging in several formats. Each layer is optimized to provide needed services to existing hospital clients and is well positioned to support future hospital network clients.

Laboratory detection of Clostridium difficile. A comparison of media and incubation systems.

Parallel testing for culture recovery of Clostridium difficile was performed using three selective media in each of four anaerobic incubation environmental systems. Testing was completed on 67 stool samples from 60 hospitalized patients in whom C difficile-associated diarrhea was suspected. Three different media were evaluated: CCFA (modified cycloserine-cefoxitin-fructose agar), CCFA-PRAS (CCFA, prereduced-anaerobically-sterilized) and CMBA (modified cycloserine-mannitol-blood agar). The incubation systems compared were an anaerobic chamber (Model 800 Anaerobic Environmental System, Anaerobe Systems, San Jose, CA), the anaerobic jar (BBL, Cockeysville, MD), the anaerobic Bio-Bag (BBL), and the anaerobic pouch (BBL). C difficile was found in 16 samples collected from 15 patients. Comparing recovery on the various types of media in all four anaerobic atmospheres, C difficile was recovered on all (64) CCFA plates, 56 of 64 CCFA-PRAS plates, and 43 of 64 CMBA plates (P < .03 comparing CCFA and CMBA). Of the 48 plates in each incubation system that were inoculated with specimens positive for C difficile, the organism was recovered from 43 plates in the anaerobe chamber, 41 incubated in an anaerobe jar, 40 in the Bio-Bag, and 39 incubated in the GasPak pouch, all providing similar recovery of C difficile (P = .08). The CCFA-PRAS and CMBA media demonstrated less inhibition of normal stool flora compared to the CCFA. Overall CCFA that was anaerobically reduced at least 4 hours before use, and contained the original concentration of antimicrobial agents described by George and colleagues, was superior to CMBA for recovery of C. difficile.

The deployment of a World Wide Web (W3) based medical information system.

The development of Web technologies has revolutionized information dissemination on the Internet. The University of Minnesota Hospital and Clinic's Web Clinical Information System (CIS) demonstrates the use of the Web as an infrastructure for deploying a medical information system at a fraction of the developmental cost of more traditional client server systems. This Web CIS has been deployed since December 1994. It makes available laboratory results, including a radically improved clinical microbiology reporting system, ad hoc laboratory order entry, and an embedded expert system protocol laboratory ordering system. It provides these services to any physician or patient care area with TCP (or SLIP/PPP) connection to our hospital network backbone, whether the client computer is running MS Windows, the Macintosh OS, or X-Windows. A formal evaluation of one of this systems subcomponents, the display of clinical microbiology information, demonstrated a significant savings in clinician time (43% p < .001) and substantial reduction in interpretive errors (0 vs 15 p < .01).

Effectiveness of liquid soap vs. chlorhexidine gluconate for the removal of Clostridium difficile from bare hands and gloved hands.

OBJECTIVE: To compare liquid soap versus 4% chlorhexidine gluconate in 4% alcohol for the decontamination of bare or gloved hands inoculated with an epidemic strain of Clostridium difficile. DESIGN: C difficile (6.7 log10 colony-forming units [CFU], 47% spores), was seeded onto bare or latex gloved hands of ten volunteers and allowed to dry. Half the volunteers initially washed with soap and half with chlorhexidine, followed by the other agent 1 week later. Cultures were done with Rodac plates at three sites on the hand: finger/thumbtips, the palmar surfaces of the fingers, and the palm. Statistical comparison was by paired Student's t test. RESULTS: On bare hands, soap and chlorhexidine did not differ in residual bacterial counts on the finger/thumbtips (log10 CFU, 2.0 and 2.1, P = NS) and fingers (log10 CFU, 2.4 and 2.5, P = NS). Counts were too high on bare palms to quantitate. On gloved hands, soap was more effective than chlorhexidine on fingers (log10 CFU 1.3 and 1.7, P < .01) and palms (log10 CFU 1.5 and 2.0, P < .01), but not finger/thumbtips (log10 CFU 1.6 with each, P = NS). Residual C difficile counts were lower on gloved hands than bare hands (P < 0.01 to < 0.0001). CONCLUSIONS: The two agents did not differ significantly in residual counts of C difficile on bare hands, but on gloved hands residual counts were lower following soap wash than following chlorhexidine wash. These observations support the use of either soap or chlorhexidine as a handwash for removal of C difficile, but efficacy in the prevention of C difficile transmission must be determined by prospective clinical trials.

Network analytic methods for epidemiological risk assessment.

The authors measure the efficacy of three methods for predicting the time to infection for susceptible individuals in a population undergoing an HIV epidemic. The methods differ in whether they require detailed information of the contact network and whether they require knowledge of the initial source of infection. Efficacy is evaluated using simulations for 20 different contact patterns. Only the risk score that uses both kinds of information accounts for more than 15 per cent of individual variability. The efficacy of this score ranges from 10 per cent in very unstructured populations to 60 per cent for spatially localized contact networks. This improved performance may be explained by the larger fraction of the total variability not due to the disease dynamics. When all variables are dichotomized, the two poorer methods produce odds ratios between 1.4 and 2.3. The odds ratio for the risk score with full information ranges from 2.5 to 17. Risk assessment protocols and intervention programmes are encouraged to assess contact patterns and detect sources of infection.

Activity of twenty-one antimicrobial agents including l-ofloxacin against quinolone-sensitive and -resistant, and methicillin-sensitive and -resistant Staphylococcus aureus.

There is a need to identify alternative agents to vancomycin for the treatment of infections with methicillin-resistant Staphylococcus aureus (MRSA). One candidate is the l isomer of ofloxacin (DR-3355). We tested 520 frozen MRSA isolates, 248 fresh MRSA isolates, and 375 fresh methicillin-susceptible S. aureus (MSSA) isolates from Minnesota, and 600 clinical isolates of S. aureus (150 MRSA and 450 MSSA) from Illinois. Over 90% of the MRSA strains were resistant to 32 micrograms/ml of oxacillin. Of the 520 frozen MRSA, 24% were susceptible to < or = 2 micrograms/ml ofloxacin, and an additional 74% were susceptible to ofloxacin between 8 and 16 micrograms/ml. More than 98% of all strains were susceptible to < or = 16 micrograms/ml ofloxacin or l-ofloxacin. All the quinolones had a bimodal distribution of in vitro activity, but for only ofloxacin and l-ofloxacin was activity confined to a very narrow range.

External fixators for treatment of unstable wrist fractures. A biomechanical, design feature, and cost comparison.

This study provides comparative data relative to the mechanical rigidity, cost, weight, and other features of 13 external fixators for the distal radius. It is our intent that these data be used by the practicing surgeon in the selection of a device that is appropriate to his or her practice and any given patient.

GyrA sequence analysis of Staphylococcus aureus and methicillin-resistant S. aureus strains selected, in vitro, for high-level ciprofloxacin resistance.

Four methicillin-susceptible Staphylococcus aureus and eight methicillin-resistant S. aureus (MRSA) isolates, all of which were ciprofloxacin susceptible (MIC < 2.0 micrograms/ml) were manipulated, in vitro, to achieve high-level ciprofloxacin resistance by means of up to 14 passages onto media containing increasing concentrations of ciprofloxacin. Resistance to ciprofloxacin at a concentration of at least 512 micrograms/ml was achieved in all 12 isolates tested. This resistance was continually detected during weekly passage on antibiotic-free media for 12 weeks. The parent and daughter cells from four strains had their gyrA sequenced from amino acid (aa) codons 70-100, the region of previous mutations in high level quinolone-resistant S. aureus. Mutations at aa codon 84 were seen in three of four strains, but appeared at varying levels of ciprofloxacin resistance. High-level resistance of S. aureus and MRSA to ciprofloxacin can be developed in vitro using multiple exposures to incremental concentrations of the drug. It is apparently due to multiple mechanisms and, once established, remains stable over time.

Utility of slide centrifuge gram's stain versus quantitative culture for diagnosis of urinary tract infection.

The slide centrifuge (cytospin) Gram's-stain technique has been shown in previous studies to be a sensitive technique for detecting bacteriuria when compared to culture. The method concentrates urine sediment in a small defined area on a glass slide for Gram's staining. A positive test provides morphologic information about suspected pathogens. This study evaluated the cytospin technique using 788 urine specimens, on which routine culture was simultaneously performed, and compared both with clinical evidence for urinary tract infection. One hundred twelve of these specimens, which were cytospin positive and had a culture growing more than 100,000 CFU/mL, were assumed, by definition, to represent true urinary tract infection. Five hundred twenty-six specimens had negative cytospin and negative culture results (less than 1,000 CFU/mL) and were assumed, by definition, to rule out the diagnosis of urinary tract infection. Clinical data were evaluated for 56 cytospin-positive specimens in which culture results were less than 100,000 CFU/mL. Of these specimens, 37 were false positive (no clinical evidence of urinary tract infection), 9 had clinical evidence of urinary tract infection, and for the remaining 10, data regarding clinical status could not be interpreted. Seventy-one specimens were cytospin negative, with cultures growing more than 1,000 CFU/mL. Of these, only one patient had clinical evidence of a urinary tract infection, and his culture result was less than 10,000 CFU/mL. The predictive value of a negative cytospin test was 99.8% compared to clinical information, whereas the predictive value of a negative culture (less than 100,000 CFU/mL) was 98.4%.