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Lawrence Brown

Publications and source records attributed to Lawrence Brown.

10 recordsLinked to original sources

Achieving durable glucose control in the intensive care unit without hypoglycaemia: a new practical IV insulin protocol.

BACKGROUND: Hyperglycaemia occurs in a substantial portion of critically ill patients in our intensive care units. Near normalization of elevated blood glucose levels with IV insulin may improve outcome. However, currently published IV insulin protocol are not ideal; most are relatively complex and often result in hypoglycaemia. We designed a protocol that would be practical to use while incorporating the necessary complexities required to achieve good glucose control, coupled with a low incidence hypoglycaemia. METHODS: The essential part of the protocol is a matrix specifying the amount by which an insulin flow rate is to be changed. The intersection of the current and the previous blood glucose values on the matrix locates the appropriate cell containing the required change in insulin flow rate. No additional calculations or tables are required. RESULTS: The initial glucose level obtained by blood glucose meter (BGM) averaged 253.5 +/- 95.6 mg/dL and fell below 140 within 9.3 h on the protocol. The average BGM on the protocol was 133.5 +/- 43.9 mg/dL. Only 0.09% of all glucose values were <40 mg/dL and insulin had to be held only 2.2% of the time on the protocol. Physician input was not required and nursing accuracy in applying the protocol was greater than 94%. This protocol has been adopted as the default IV insulin protocol for the NorthShore-LIJ Health System and several other medical centers. CONCLUSION: A practical IV insulin protocol that has been extensively tested is presented. The protocol has been implemented at multiple institutions indicating its ease of use and excellent results.

Aged↗

Biological monitoring and surveillance results of Gulf War I veterans exposed to depleted uranium.

OBJECTIVE: To relate medical surveillance outcomes to uranium biomonitoring results in a group of depleted uranium (DU)-exposed, Gulf War I veterans. METHODS: Thirty-two veterans of Gulf War I who were victims of 'friendly fire' involving DU weapons, in whom exposure assessment can accurately be measured, had urine uranium concentrations determined using ICP-MS technology. Clinical laboratory parameters were measured and related to urine uranium concentrations. Data were examined by stratifying the cohort into a low U group, <0.10 mug/g creatinine versus a high U group, >/=0.10 mug/g creatinine and assessing differences between groups. RESULTS: Over a decade after first exposure, soldiers possessing embedded DU fragments continue to excrete elevated concentrations of uranium in urine. No clinically significant uranium related health effects were observed in blood count, blood chemistries including renal markers, neuropsychological measures, and semen quality or genotoxicity measures. Markers of early changes in renal glomerular and tubular function were not statistically different between groups; however, genotoxicity measures continue to show subtle, mixed results. CONCLUSION: Persistent urine uranium elevations continue to be observed more than 12 years since first exposure. Despite this, renal and other clinical abnormalities were not observed, likely due to the 'relatively' low uranium burden in this cohort compared to historical uranium-exposed occupational groups. Continuing surveillance is indicated, however, due to the on-going nature of the exposure. These results are an important finding in light of the on-going controversy regarding health effects observed in soldiers of the Gulf War and other conflicts, whose uranium exposure assessment is unable to be accurately determined.

Adolescent↗

Health effects of depleted uranium on exposed Gulf War veterans: a 10-year follow-up.

Medical surveillance of a group of U.S. Gulf War veterans who were victims of depleted uranium (DU) "friendly fire" has been carried out since the early 1990s. Findings to date reveal a persistent elevation of urine uranium, more than 10 yr after exposure, in those veterans with retained shrapnel fragments. The excretion is presumably from ongoing mobilization of DU from fragments oxidizing in situ. Other clinical outcomes related to urine uranium measures have revealed few abnormalities. Renal function is normal despite the kidney's expected involvement as the "critical" target organ of uranium toxicity. Subtle perturbations in some proximal tubular parameters may suggest early although not clinically significant effects of uranium exposure. A mixed picture of genotoxic outcomes is also observed, including an association of hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutation frequency with high urine uranium levels. Findings observed in this chronically exposed cohort offer guidance for predicting future health effects in other potentially exposed populations and provide helpful data for hazard communication for future deployed personnel.

Adult↗

Identification of substrate binding sites in enzymes by computational solvent mapping.

Enzyme structures determined in organic solvents show that most organic molecules cluster in the active site, delineating the binding pocket. We have developed algorithms to perform solvent mapping computationally, rather than experimentally, by placing molecular probes (small molecules or functional groups) on a protein surface, and finding the regions with the most favorable binding free energy. The method then finds the consensus site that binds the highest number of different probes. The probe-protein interactions at this site are compared to the intermolecular interactions seen in the known complexes of the enzyme with various ligands (substrate analogs, products, and inhibitors). We have mapped thermolysin, for which experimental mapping results are also available, and six further enzymes that have no experimental mapping data, but whose binding sites are well characterized. With the exception of haloalkane dehalogenase, which binds very small substrates in a narrow channel, the consensus site found by the mapping is always a major subsite of the substrate-binding site. Furthermore, the probes at this location form hydrogen bonds and non-bonded interactions with the same residues that interact with the specific ligands of the enzyme. Thus, once the structure of an enzyme is known, computational solvent mapping can provide detailed and reliable information on its substrate-binding site. Calculations on ligand-bound and apo structures of enzymes show that the mapping results are not very sensitive to moderate variations in the protein coordinates.

Algorithms↗

Algorithms for computational solvent mapping of proteins.

Computational mapping methods place molecular probes (small molecules or functional groups) on a protein surface to identify the most favorable binding positions by calculating an interaction potential. We have developed a novel computational mapping program called CS-Map (computational solvent mapping of proteins), which differs from earlier mapping methods in three respects: (i) it initially moves the ligands on the protein surface toward regions with favorable electrostatics and desolvation, (ii) the final scoring potential accounts for desolvation, and (iii) the docked ligand positions are clustered, and the clusters are ranked on the basis of their average free energies. To understand the relative importance of these factors, we developed alternative algorithms that use the DOCK and GRAMM programs for the initial search. Because of the availability of experimental solvent mapping data, lysozyme and thermolysin are considered as test proteins. Both DOCK and GRAMM speed up the initial search, and the combined algorithms yield acceptable mapping results. However, the DOCK-based approaches place the consensus site farther from its experimentally determined position than CS-Map, primarily because of the lack of a solvation term in the initial search. The GRAMM-based program also finds the correct consensus site for thermolysin. We conclude that good sampling is the most important requirement for successful mapping, but accounting for desolvation and clustering of ligand positions also help to reduce the number of false positives.

2-Propanol↗

Developing research criteria to define medical necessity in emergency medical services.

"The Neely Conference: Developing Research Criteria to Define Medical Necessity in EMS" convened emergency medical services (EMS) physicians, researchers, administrators, providers, and federal agency representatives to begin the development of a set of uniform triage criteria and outcome measures that could be used to study and evaluate medical necessity among EMS patients. These standardized criteria might be used in research studies examining EMS dispatch and response (e.g., dispatch triage protocols, alternative response configurations), and EMS treatment and transport (e.g., field triage protocols, alternative care destinations). The conference process included review and analysis of the literature, expert judgment, and consensus building. There was general agreement on the following: 1. Any dispatch triage or field triage system that is developed must be designed to offer patients alternatives to EMS, not to refuse care to patients. 2. It is theoretically possible to develop a set of clinical criteria for need. Some groups of patients will clearly need a traditional EMS response and other groups will not, but this has yet to be defined. 3. In addition to clinical criteria, certain social and other nonclinical criteria such as pain or potential abuse may be used to justify a response. 4. Communication barriers, patient age, special needs, and other conditions complicate patient assessment but should not exclude patients from consideration for alternate triage or transport. 5. These research questions are important, and standard sets of outcome measures are needed so that different studies and innovative programs can be compared.

Adult↗

The 2001 National Pharmacy Consumer Survey.

OBJECTIVES: To determine the types of pharmacy services used by consumers, to determine what sources they accessed for information on health and prescription drugs, and to assess their satisfaction with these information sources. DESIGN: Telephone survey. SETTING: Households. PARTICIPANTS: Random sample of 1,201 consumers who reported having used the Internet during the previous 2 months and having filled at least one prescription within the past 6 months. RESULTS: Convenience continues to be the primary patronage motive for using a particular pharmacy, followed by price and service. Satisfaction with pharmacy services remains high, with 85% of respondents reporting being satisfied with the process of filling a new prescription and 90% being satisfied with the refill process. Exploratory analyses showed that respondents who reported they always asked questions of their pharmacists were consistently more satisfied with pharmacy services. Consumers ranked physicians and pharmacists as the first and second most important sources for drug information, and they were more satisfied with information obtained from these sources than they were with information obtained from print or electronic information sources. Thirty-six percent of respondents had searched the Internet for information on prescription medications within the past year. CONCLUSION: Convenience is still the primary determinant of pharmacy selection, and most consumers continue to use a single pharmacy. Exploratory analysis suggests a direct association between active information seeking from the pharmacist and consumers' satisfaction with pharmacy services.

Consumer Behavior↗