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Biomedical subjects

J W Snyder

Publications and source records attributed to J W Snyder.

At least 19 recordsLinked to original sources

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.

Aerobiosis↗

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.

Adult↗

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.

Adult↗

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.

Animals↗

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.

Aged↗

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.

Animals↗

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.

Apoptosis↗

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.

Acetylcholine↗

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.

Electrophoresis, Agar Gel↗

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.

Humans↗

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.

Anti-Bacterial Agents↗

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.

Autoanalysis↗

The absence of extracellular calcium potentiates the killing of cultured hepatocytes by aluminum maltolate.

Dose- and time-dependent killing of cultured rat hepatocytes was produced by aluminum maltolate (AlM), a neutral, water-soluble complex of aluminum 3-hydroxy-2-methyl-4H-pyran-4-one. Treatment with 10 mM AlM for 1 h killed 50% or more of the cells within 3 h. Removal of calcium from the culture medium or treatment with calcium channel blockers (verapamil, nifedipine, diltiazem) potentiated the cell killing. By contrast, inhibition by thapsigargin of the sequestration of intracellular calcium by the endoplasmic reticulum reduced the toxicity of AlM. In turn, activation of protein kinase C with 12-O-tetradecanoylphorbol 13-acetate or activation of protein kinase A with 8-[4-chlorophenyl-thio]adenosine 3',5'-cyclic monophosphate also reduced the toxicity of AlM. By contrast, inhibition of protein kinase activity by staurosporine potentiated the cell killing. Staurosporine, however, did not reverse the protection afforded by thapsigargin. Hepatocytes treated with AlM for 1 h were rescued by adding deferoxamine as late as 90 min following the removal of AlM, whereas pretreatment for 1 h with deferoxamine did not prevent the toxicity of AlM. ATP depletion did not precede loss of viability. Pharmacologic probes excluded oxidative stress as a mechanism of lethal injury by AlM, and inhibition of protein synthesis by cycloheximide did not protect the hepatocytes, thereby excluding activation of a cell death program. These data define a new model in which aluminum kills liver cells by a mechanisms distinct from previously recognized pathways of lethal cell injury. It is hypothesized that aluminum binds to cytoskeletal proteins intimately associated with the plasma membrane. This interaction eventually disrupts the permeability barrier function of the cell membrane, an event that heralds the death of the hepatocyte. The intracellular calcium ion concentration and protein phosphorylation may modify the interaction of aluminum with its critical targets. Alternatively, aluminum may inhibit the phosphorylation of cytoskeletal elements, thereby interfering with their function.

Aluminum↗

Occupational fatality and persistent neurological sequelae after mass exposure to hydrogen sulfide.

Exposure to hydrogen sulfide (H2S) has been associated with death as well as survival following coma with or without hypoxic brain damage. The release of H2S at a beachfront construction site led to the emergency evaluation and treatment of 37 people, with six admissions and one death. At least one victim, who underwent extensive therapy with hyperbaric oxygen, developed persistent neurological sequelae. Despite increased awareness of the potentially life-threatening consequences of exposure to H2S, significant poisoning continues to occur, even in workplaces where the hazards are well-known and can be avoided. Recommended therapy includes nitrites, hyperbaric oxygen, and supportive care, but documentation of efficacy is lacking. Because patients with chronic neurological sequelae after acute H2S exposure continue to be reported, we suggest that any survivor of H2S poisoning who presents in coma or who manifests objectively verifiable evidence of neurotoxicity on physical examination or lab testing should undergo baseline and annual neurological and neuropsychological testing for at least five years. This approach could standardize and enhance our knowledge of, and ability to detect, the subtle but permanent alterations of central nervous system function that follow H2S exposure.

Accidents, Occupational↗

Ca2+ depletion prevents anoxic death of hepatocytes by inhibiting mitochondrial permeability transition.

Removal of Ca2+ from the culture medium or treatment with the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) prevented the killing of rat hepatocytes by anoxia and rotenone, but not by cyanide. Neither manipulation prevented the loss of the mitochondrial membrane potential or the depletion of ATP. A mitochondrial permeability transition (MPT) was demonstrated in digitonin-permeabilized hepatocytes as an increased [3H]sucrose-accessible space sensitive to cyclosporin A (CyA). Ca2+ depletion by either means prevented the MPT measured in intact cells made anoxic or treated with rotenone. In isolated mitochondria deenergized by rotenone, BAPTA-AM prevented the MPT induced by palmitoyl CoA. By contrast, in isolated mitochondria deenergized by cyanide, BAPTA-AM alone did not prevent the MPT. Rather, BAPTA-AM plus CyA were required. Similarly, the killing of cultured hepatocytes by cyanide was prevented by BAPTA-AM plus CyA, but not by either agent alone. The MPT in intact cells treated with cyanide was also prevented by BAPTA-AM plus CyA. These data define a specific requirement for Ca2+ in the killing of hepatocytes that follows the inhibition of electron transport. A model is presented in which the MPT depends on factors that modulate the sensitivity of the permeability transition to the matrix concentration of Ca2+.

Adenosine Triphosphate↗

An in vitro model of ethanol-dependent liver cell injury.

Primary cultures of adult rat hepatocytes were incubated (6 to 96 hr) with 50 to 150 mmol/L ethanol, 0.5 mmol/L linoleate, 0.5 mmol/L palmitate, 0.5 mmol/L 4-methylpyrazole, 0 to 25 mumol/L vitamin E phosphate or selected combinations of these agents. Agent-dependent changes in liver cell viability (AST release and reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and function (phospholipid peroxidation, hydrolysis, biosynthesis and triacylglycerol biosynthesis) were determined. The influence of ethanol on liver cell function and viability was dose and incubation time dependent. Short periods (24 hr or less) of exposure to 100 mmol/L ethanol increased liver cell triacylglycerol biosynthesis and phospholipid hydrolysis, peroxidation and biosynthesis without altering cell viability. However, longer periods (72 hr or more) of exposure to 100 or 150 mmol/L ethanol resulted in significant reductions (30% to 50%) in cell viability, function and phosphatidylcholine biosynthesis and content. The ethanol-dependent decreases in cell function and viability were potentiated by linoleate and reduced by vitamin E phosphate, palmitate and 4-methylpyrazole. These results suggest that ethanol-induced liver cell injury in vitro is not a result of ethanol per se, but factors such as acetaldehyde or oxyradicals produced as a consequence of ethanol metabolism. Therefore the incubation of cultured hepatocytes with ethanol may be an appropriate model in vitro for determining the mechanisms by which ethanol intake disrupts liver cell function in vivo.

Animals↗