Mealtime fast-acting insulin aspart versus insulin aspart for controlling postprandial hyperglycaemia in people with insulin-resistant Type 2 diabetes.

AIM: This post hoc analysis explored whether mealtime fast-acting insulin aspart treatment provided an advantage in postprandial plasma glucose (PPG) control vs. insulin aspart in people with Type 2 diabetes receiving high doses of bolus insulin. METHODS: A post hoc, post-randomization, subgroup analysis of a 26-week, randomized, double-blind, treat-to-target trial (onset 2) that compared mealtime fast-acting insulin aspart vs. mealtime insulin aspart, both in a basal-bolus regimen, in people with Type 2 diabetes uncontrolled on basal insulin therapy and metformin. At the end of trial, the impact of fast-acting insulin aspart and insulin aspart on PPG control was assessed with a standard liquid meal test and participants were grouped into three post-randomization subgroups: meal test bolus insulin dose ≤ 10 units per dose (n = 171), > 10-20 units per dose (n = 289) and > 20 units per dose (n = 146). RESULTS: A statistically significant treatment difference in favour of fast-acting insulin aspart vs. insulin aspart was observed for the change in PPG increment at all post-meal time points (from 1 to 4 h) for those in the > 20 units bolus insulin subgroup. There was no difference in the magnitude of change from baseline in HbA1c level between fast-acting insulin aspart and insulin aspart in any of the bolus insulin dose subgroups (data herein). CONCLUSION: Fast-acting insulin aspart may hold promise as a more effective treatment compared with insulin aspart for controlling PPG in people with insulin-resistant Type 2 diabetes.

Direct comparison of the BD phoenix system with the MicroScan WalkAway system for identification and antimicrobial susceptibility testing of Enterobacteriaceae and nonfermentative gram-negative organisms.

The Phoenix automated microbiology system (BD Diagnostics, Sparks, MD) is designed for the rapid identification (ID) and antimicrobial susceptibility testing (AST) of clinically significant human bacterial pathogens. We evaluated the performance of the Phoenix instrument in comparison with that of the MicroScan WalkAway system (Dade Behring, West Sacramento, CA) in the ID and AST of gram-negative clinical strains and challenge isolates of Enterobacteriaceae (n = 150) and nonfermentative gram-negative bacilli (NFGNB; 45 clinical isolates and 8 challenge isolates). ID discrepancies were resolved with the API 20E and API 20NE conventional biochemical ID systems (bioMerieux, Durham, NC). The standard disk diffusion method was used to resolve discordant AST results. The overall percentages of agreement between the Phoenix ID results and the MicroScan results at the genus and species levels for clinical isolates of Enterobacteriaceae were 98.7 and 97.7%, respectively; following resolution with conventional biochemical testing, the accuracy of the Phoenix system was determined to be 100%. For NFGNB, the levels of agreement were 100 and 97.7%, respectively. Both systems incorrectly identified the majority of the uncommon nonfermentative nonpseudomonal challenge isolates recovered from cystic fibrosis patients; these isolates are not included in the databases of the respective systems. For AST of Enterobacteriaceae, the rate of complete agreement between the Phoenix results and the MicroScan results was 97%; the rates of very major, major, and minor errors were 0.3, 0.2, and 2.7%, respectively. For NFGNB, the rate of complete agreement between the Phoenix results and the MicroScan results was 89.1%; the rates of very major, major, and minor errors were 0, 0.5, and 7.7%, respectively. Following the confirmatory testing of nine clinical isolates initially screened by the MicroScan system as possible extended-spectrum-beta-lactamase (ESBL)-producing organisms (seven Klebsiella pneumoniae isolates and two Escherichia coli isolates), complete agreement was achieved for eight isolates (one ESBL positive and seven negative); one false positive was obtained with the Phoenix instrument. The MicroScan system correctly detected the 10 ESBL challenge isolates, versus the 6 detected by the Phoenix system. Overall, there was good correlation between the Phoenix instrument and the MicroScan system for the ID and AST of Enterobacteriaceae and common NFGNB. The Phoenix system is a reliable method for the ID and AST of the majority of clinical strains encountered in the clinical microbiology laboratory. Until additional performance data are available, results for all Klebsiella pneumoniae or Klebsiella oxytoca and E. coli isolates screened and confirmed as ESBL producers by any automated system should be confirmed by alternate methods prior to the release of final results.

Evaluation of a plastic nonvented aerobic blood culture bottle for use with the BacT/ALERT microbial detection system.

The current BacT/ALERT SA (BTA SA) aerobic blood culture bottle is made from glass, does not require venting, and contains a liquid emulsion sensor (LES). Its performance has been shown to be equivalent to that of the vented standard aerobic culture bottle. A further-improved version of the BTA SA bottle, designated the BacT/ALERT plastic SA (BTA PSA) culture bottle, is made from clear plastic to prevent breakage, does not require venting, and contains a modified LES (LES 2) to reduce the possibility of false positives. The BTA PSA provides a practical alternative to the current glass version of this bottle. The plastic bottle is also comparable to the current glass bottle in transparency and growth performance and additionally minimizes the exposure to infectious agents due to glass bottle breakage.

Health hazards in drawing and painting.

Most health hazards in drawing and painting fall into two primary categories: volatile organic solvents used in many painting mediums and fixatives for dry drawing mediums; and respirable powders and dusts such as powdered pigments and dyes, which may be toxic and/or suspected or known carcinogens. User safeguards, such as appropriate ventilation and protective attire, and protection of the environment through careful emission and waste disposal, can be readily implemented with the education of artists and their employers. This chapter succinctly outlines the risk factors, symptomatology, and remedies to assist medical professionals in providing diagnosis and treatment.

A systematic approach to risk stratification and intervention within a managed care environment improves diabetes outcomes and patient satisfaction.

OBJECTIVE: To determine whether a comprehensive diabetes management program that included risk stratification and social marketing would improve clinical outcomes and patient satisfaction within a managed care organization (MCO). RESEARCH DESIGN AND METHODS: The 12-month prospective trial was conducted at primary care clinics within a MCO and involved 370 adults with diabetes. Measurements included 1) the frequency of dilated eye and foot examinations, microalbuminuria assessment, blood pressure measurement, lipid profile, and HbA(1c) measurement; 2) changes in blood pressure, lipid levels, and HbA(1c) levels; and 3) changes in patient satisfaction. RESULTS: Complete data are reported for the 193 patients who had been enrolled for 12 months; life table analysis is reported for all patients who remained enrolled at the study's end as well as for a comparative control group of 623 patients. For the 193 patients for whom 12-month data were available, the number of patients in the low-risk category (HbA(1c) <7%) increased by 51.1%. A total of 97.4% of patients with an HbA(1c) >8% at baseline had a change in treatment regimen. Patients at the highest risk for coronary heart disease (LDL >130 mg/dl) decreased from 25.4% at baseline to 20.2%. Patients with a blood pressure <130/85 mmHg increased from 23.8 to 44.6%. Of these patients, 63.0% had changes in medication. Patients and providers expressed significant increases in satisfaction with the program. CONCLUSIONS: The program was successful in initiating the recommended changes in the diabetic therapeutic regimen, resulting in improved glycemic control, increased monitoring/management of diabetic complications, and greater patient and provider satisfaction. These results should have great significance in the design of future programs in MCOs aimed at improving the care of people with diabetes and other chronic diseases.

The role of the clinical laboratory in managing chemical or biological terrorism.

BACKGROUND: Domestic and international acts of terrorism using chemicals and pathogens as weapons have recently attracted much attention because of several hoaxes and real incidents. Clinical laboratories, especially those affiliated with major trauma centers, should be prepared to respond rapidly by providing diagnostic tests for the detection and identification of specific agents, so that specific therapy and victim management can be initiated in a timely manner. As first-line responders, clinical laboratory personnel should become familiar with the various chemical or biological agents and be active participants in their local defense programs. APPROACH: We review the selected agents previously considered or used in chemical and biological warfare, outline their poisonous and pathogenic effects, describe techniques used in their identification, address some of the logistical and technical difficulties in maintaining such tests in clinical laboratories, and comment on some of the analytical issues, such as specimen handling and personal protective equipment. CONTENT: The chemical agents discussed include nerve, blistering, and pulmonary agents and cyanides. Biological agents, including anthrax and smallpox, are also discussed as examples for organisms with potential use in bioterrorism. Available therapies for each agent are outlined to assist clinical laboratory personnel in making intelligent decisions regarding implementation of diagnostic tests as a part of a comprehensive defense program. SUMMARY: As the civilian medical community prepares for biological and chemical terrorist attacks, improvement in the capabilities of clinical laboratories is essential in supporting counterterrorism programs designed to respond to such attacks. Accurate assessment of resources in clinical laboratories is important because it will provide local authorities with an alternative resource for immediate diagnostic analysis. It is, therefore, recommended that clinical laboratories identify their current resources and the extent of support they can provide, and inform the authorities of their state of readiness.

Linking pharmacy and laboratory data to assess the appropriateness of care in patients with diabetes.

OBJECTIVE: To use pharmacy and laboratory data to assess diabetes care within a medical group and between medical groups and to determine dispensing patterns and the extent to which providers change therapy based on HbA1c results. RESEARCH DESIGN AND METHODS: Participating groups submitted 1 year of data for continuously enrolled patients. Required data included date of birth, all diabetes-specific prescriptions (oral hypoglycemic agents and insulin), date of prescription, National Drug Code, all HbA1c values, lower and upper normal limits, and date of testing. RESULTS: Few changes in therapy were noted despite the large percentages of patients with suboptimal control. Nearly 90% of the patients treated with medications received a monotherapy regimen involving one of three therapeutic agents: sulfonylureas, metformin, or insulin. More than three-fourths of the patients remained on the same therapy during the observation period despite the fact that 27% of these patients had HbA1c values > or = 8%. Nearly one-fifth (18%) of patients had an HbA1c level of > or = 8% and no further testing for at least 90 days after the "actionable" HbA1C result was obtained. Furthermore, 54% of patients with actionable HbA1c results did not have a change in therapy initiated after the result was available. CONCLUSIONS: The American Diabetes Association recommendations to act on HbA1c values > or = 8% and to follow up regularly on patients found to be in suboptimal control do not appear to be applied in a consistent manner based on the pharmacy and laboratory data analyzed in this sample.

Venomous snakebites in an urban area: what are the possibilities?

OBJECTIVE: To estimate the number of different species of venomous snakes privately kept in a large urban area. METHODS: An anonymous survey of potential snake owners in the Philadelphia urban and suburban area. The survey was mailed to members of the Philadelphia Herpetological Society. In addition, the survey was published in 2 herpetological newsletters and online in the Herpetology Network. RESULTS: One hundred sixty responses were obtained during a 6-month period. Ownership of 74 different varieties of venomous snakes was reported. Antivenin was not locally available for 13 of these species. CONCLUSION: A wide variety of venomous captive snakes can be found in the private sector. The potential for having to treat an envenomation requires the emergency physician to maintain an education of snakebite management options, including the various antivenin options available in their geographical location.

Clinical comparison of nonvented aerobic BacT/Alert blood culture bottle and standard aerobic bottle for detection of microorganisms in blood.

The current BacT/Alert standard aerobic (VA) blood culture bottle was redesigned and designated a nonvented aerobic (NVA) culture bottle; this bottle does not require venting. A total of 3,873 sets of blood samples for culture were obtained from adult patients with suspected bacteremia or fungemia. The NVA bottle showed performance equivalent to that of the VA bottle for recovery and speed of detection of microorganisms from blood without the need for venting the bottle.

Common bacteria whose susceptibility to antimicrobials is no longer predictable.

The widespread use of antibiotics has been responsible for the development of numerous problems including the emergence of multidrug resistant bacteria, increased number of nosocomial- and community-acquired infections, less than optimal patient outcome, and increased health care costs. Of equal concern is the emergence of resistance in clinical isolates to antibiotics that were once considered "standard" with predictable in vitro susceptibility patterns. Such resistance has been especially notable in organisms that are commonly encountered in a variety of infections including, Streptococcus pneumoniae, Staphylococcus aureus. Enterococci, Klebsiella pneumoniae, and Escherichia coli. It is important for the clinical microbiology laboratory to provide the practicing clinician with accurate and timely antimicrobial susceptibility information which requires the application of standardized and approved in vitro testing methods. The laboratory also serves as a sentinel by maintaining an active monitoring and surveillance program in which current in vitro susceptibility patterns can be compared with local, regional, and national data bases.

Prion infections in Creutzfeldt-Jakob disease and its variants.

Prions (PrP(Sc)) are proteinaceous infectious particles that occur as sporadic (85 percent), infectious (iatrogenic) (5 percent) or hereditary (10 percent) diseases in humans and animals. These unique infectious agents produce a spongiform change in the central nervous system without any inflammation, inclusion bodies or apparent antibody response. A helper (X) protein and genetic predisposition appear to be required to establish the infection, which seems associated with a post-translational change of a normal protein (PrP(C)) encoded by a gene on human chromosome 20. Sporadic human prion disease (Creutzfeldt-Jakob disease) is the most common form of human transmissible spongiform encephalopathy. Nevertheless, it is undoubtedly under-recognized as a result of both low autopsy rates and confusion with other dementing diseases like Alzheimer's disease. Although no therapy is currently available for this infectious dementia, which has a prolonged incubation period, these unfortunate victims should be offered supportive care and postmortem examinations. Universal precautions will protect laboratorians from this infectious, but not contagious, disease.

In vivo measurement of hemodialyzer fiber bundle volume: theory and validation.

BACKGROUND: Fiber bundle volume (FBV), the space within the blood compartment of hollow fiber dialyzers, may decrease during treatment due to clotting. The clots may be flushed out of the dialyzer prior to measurements of FBV by dialyzer reprocessing equipment and a significant drop in FBV during the session may go unrecognized. METHODS: FBV was measured (1) from the transit time of a saline bolus passing through the dialyzer as recorded by ultrasound dilution sensors placed on the arterial and venous blood lines; (2) from the change in blood concentration induced by a step change in the rate of ultrafiltration as recorded by the venous sensor. RESULTS: In vitro FBV ranged from 47 to 121 ml. Paired absolute differences between the ultrasound and volumetric measurements (flushing saline out of the dialyzer into a graduated cylinder) were 0.16 +/- 4.23% (N = 42) and 2.10 +/- 7.26% (N = 13) for the bolus and ultrafiltration methods, respectively. In vivo reproducibility of the bolus and ultrafiltration methods were 2.65 +/- 2.11% (N = 122) and 3.79 +/- 3.93% (N = 32), respectively. During 31 treatments the FBV by dilution showed an average decrease of 4.17 +/- 8.60%, and in 6 cases FBV fell more than 10%, while measurements of the same FBV by reuse equipment showed an increase of 0.99 +/- 5.82%, P < 0.01. CONCLUSIONS: FBV measured by the dilution methods was accurate and reproducible. Preliminary results suggest that in vivo FBV may differ significantly from results reported by reprocessing machines.

N-acetylcysteine enhances endothelium-dependent vasorelaxation in the isolated rat mesenteric artery.

STUDY HYPOTHESIS: Previous studies have suggested that N-acetylcysteine (NAC) may confer additional protection in acetaminophen (APAP) overdose by improving hepatic microcirculation. We hypothesize that NAC enhances release of nitric oxide (NO) from the vasculature. METHODS: Sprague-Dawley rat superior mesenteric artery rings were suspended in oxygenated Krebs-Henseleit tissue baths and contracted with U-46619 (a thromboxane A2-mimetic). In part 1, the effect of NAC on endothelial cell (EC) release of NO was assessed by measurement of vasorelaxation induced by acetylcholine (ACh, an EC-dependent vasorelaxor) in the presence and absence of NAC. In part 2, the effect of glutathione (a major component of NAC hepatoprotection) was examined by measuring ACh-induced vasorelaxation in rings from rats treated with L-buthionine sulfoxamine (BSO, a glutathione synthesis inhibitor). Data were analyzed by repeated-measures ANOVA. RESULTS: Addition of 15 to 30 mmol/L NAC after ring contraction had no direct vasodilatory effect. By contrast, pretreatment of rings with NAC (15 mmol/L) enhanced vasorelaxation induced by ACh (95.0% +/- 7.9% versus 62.3% +/- 7.6% for control; ACh dose, 1 mumol/L; P < .001) or by A23187, a receptor-independent, NO-mediated vasodilator (91.6% +/- 9.6% versus 68.3% +/- 12.1% for control; A23187 dose, 1 mumol/L; P < .001). In rings from BSO-treated rats, NAC also enhanced vasorelaxation (76.5% +/- 7.1%; P < .001 versus control), but to a lesser degree than in nontreated rats. CONCLUSION: NAC enhances endothelium-dependent vasodilation in an isolated rat mesenteric artery ring preparation. In addition to its antioxidant effects, NAC may decrease APAP hepatotoxicity by stimulating NO production and improving microvascular circulation.

Vancomycin-resistant enterococcus in end-stage renal disease.

The percentage of nosocomial vancomycin-resistant enterococci (VRE) has been increasing rapidly in the United States. This has recently resulted in recommendations to reserve vancomycin use for cases with proven resistance to other antimicrobials. We prospectively investigated the incidence of VRE in our dialysis population and compared it with a control group of 40 clinic patients with chronic renal insufficiency (CRI) who had a serum creatinine level greater than 1.5 mg/dL, but were not undergoing dialysis. The incidence of VRE on our campus is almost 10%, which is similar to US data. We studied 50 chronic hemodialysis (HD) patients and 50 peritoneal dialysis (PD) patients. Each patient had a rectal swab test performed and cultured for the presence of enterococci. Antimicrobial exposures over the 6 months before the initial swab test were reviewed in each patient. At least one repeated swab test was performed in 30 CRI, 45 HD, and 37 PD patients. From the initial swab culture, vancomycin-sensitive enterococci (VSE) were isolated in 65% of CRI, 54% of HD, and 70% of PD patients. No CRI or HD patients had VRE isolated and 2% (1 of 50) of PD patients had VRE isolated. The remaining patients had no enterococci isolated. Review of antimicrobial exposures in the 6 months before the initial swab test showed 0% of CRI, 32% of HD, and 36% of PD patients received vancomycin. Other antimicrobials were administered to 40% of CRI, 46% of HD, and 78% of PD patients in the same time period. In the month immediately preceding the initial swab test, 0% of CRI, 12% of HD, and 22% of PD patients received vancomycin and 18% of CRI, 20% of HD, and 36% of PD patients received other antimicrobials. Results from repeated cultures showed that 57% of CRI, 40% of HD, and 38% of PD patients changed their culture status related to VSE, VRE, or no enterococci present. Cultures of 342 swabs from 140 patients yielded three VRE isolates in two patients. We conclude that despite the frequent use of vancomycin and other antimicrobials, the incidence of VRE in our renal population is less than the reported incidence. Given this lack of VRE isolates, we recommend the continued judicious use of vancomycin in treating renal patients and continued enterococcal sensitivity surveillance.

The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition.

Stably transfected Jurkat T cells were produced in which Bax expression is inducible by muristerone A. The cell death resulting from induction of the overexpression of Bax was prevented by inhibition of the mitochondrial permeability transition (MPT) with cyclosporin A (CyA) in combination with the phospholipase A2 inhibitor aristolochic acid (ArA). The caspase-3 inhibitor Z-Asp-Glu-Val aspartic acid fluoromethylketone (Z-DEVD-FMK) had no effect on the loss of viability. The MPT was measured as the CyA plus ArA-preventable loss of the mitochondrial membrane potential (DeltaPsim). The MPT was accompanied by the release of cytochrome c from the mitochondria, caspase-3 activation in the cytosol, cleavage of the nuclear enzyme poly(ADP-ribose)polymerase (PARP), and DNA fragmentation, all of which were inhibited by CyA plus ArA. Z-DEVD-FMK had no effect on the loss of DeltaPsim and the redistribution of cytochrome c but did prevent caspase-3 activation, PARP cleavage, and DNA fragmentation. It is concluded that Bax induces the MPT, a critical event in the loss of cell viability. In addition to the cell death, the MPT mediates other typical manifestations of apoptosis in this model, namely release of cytochrome c, caspase activation with PARP cleavage, and DNA fragmentation.

A combined molecular approach to screen for mec gene variants from methicillin-resistant Staphylococcus aureus.

Previous reports have suggested a common origin for all methicillin resistance (mec) genes from methicillin-resistant Staphylococcus aureus (MRSA) isolates examined so far. The purpose of this study was to explore several molecular methods for screening MRSA isolates from different sources and, in some cases, with varying phenotypes. Eighty MRSA isolates from three teaching hospitals in the University of Louisville Medical Center were compared with MRSAs from a hospital in southern California and with methicillin-sensitive S. aureus isolates. The methods were used to detect the presence of mec gene and to screen for any polymorphisms in these genes for the respective strains. The mec gene for each isolate was amplified via the polymerase chain reaction, and each polymerase chain reaction product was compared to the others by restriction enzyme digestion, denaturing-gradient gel electrophoresis, and mutation detection enhancement. By these criteria, the mec genes from the 80 MRSA strains in this study seemed to be identical. Such a finding was not unexpected and supported the existing hypothesis of a common ancestor for all mec genes isolated in MRSA isolates. However, the combination of methods used in this study may facilitate screening of MRSA strains in population studies as mec gene variants begin to emerge.

The role of the clinical laboratory in occupational medicine.

The pre-analytic, analytic, and post-analytic stages of laboratory testing present challenges to the attainment of accurate and timely information. These include sampling errors, quality control, and interpretation of results. Learning about the benefits and limitations of specific tests allows the physician to use the laboratory more productively and cost-effectively.

Changes in the American health care system: crisis in the clinical laboratory.

American medicine is undergoing unprecedented changes, and the resulting distortions are affecting the economics, organization and operations of all clinical laboratories. Professionals who work in these laboratories are facing administrative and economic pressures to reduce costs, to increase productivity, and to comply with proliferating new statutes and regulations. The medical 'cottage industry' in which the patient was the focus of the medical professionals' attention and endeavours is being replaced by the corporate management of many health care activities in which financial profits are being given first priority. Medical facilities, including clinical laboratories, are being bought and sold, being consolidated, or simply being closed. The clinical laboratories may be at the vortex of the maelstrom affecting American medicine. Cost pressures are encouraging further automation and retraining of laboratory staffs. If the leaders in laboratory medicine are unable to accomplish the necessary tasks to meet the new challenges, there inevitably is a non-medical, non-scientific financial manager at hand who is willing to define the changes and the desired outcome. Because of the rapidity of the changes taking place, it is not possible to predict with any confidence the modifications that will achieve a permanent status or the degree to which medical professionals will remain masters of their fates. The evolving health care system will become less costly, more technologically advanced, and a more challenging system in which to work.