Identification and characterization of enzymes involved in the biosynthesis of pyrimidine nucleoside antibiotics.

Covering: up to September 2020 Hundreds of nucleoside-based natural products have been isolated from various microorganisms, several of which have been utilized in agriculture as pesticides and herbicides, in medicine as therapeutics for cancer and infectious disease, and as molecular probes to study biological processes. Natural products consisting of structural modifications of each of the canonical nucleosides have been discovered, ranging from simple modifications such as single-step alkylations or acylations to highly elaborate modifications that dramatically alter the nucleoside scaffold and require multiple enzyme-catalyzed reactions. A vast amount of genomic information has been uncovered the past two decades, which has subsequently allowed the first opportunity to interrogate the chemically intriguing enzymatic transformations for the latter type of modifications. This review highlights (i) the discovery and potential applications of structurally complex pyrimidine nucleoside antibiotics for which genetic information is known, (ii) the established reactions that convert the canonical pyrimidine into a new nucleoside scaffold, and (iii) the important tailoring reactions that impart further structural complexity to these molecules.

The emergency department care of hemodialysis patients.

AIMS: To describe the emergency department (ED) presentation, evaluation and disposition of maintenance hemodialysis (HD) patients. MATERIALS AND METHODS: A retrospective review of adult HD patients seen 1/1-12/31/97. The following was collected: demographics, mode of arrival, chief complaint, etiology of renal failure, evaluation, treatment, disposition, length of stay and facility charges. During the study period, this tertiary care ED had an annual adult census of 45,000. No clinical pathways were in place. RESULTS: 143 patients made 355 visits: 351 charts were available. Mean patient age was 51 (range 20-86), 62% were male, 51% were white. 70% presented from home, 26% from dialysis. EMS transported 32%. Medicare insured 78%. Etiologies of renal failure included hypertension (33%), diabetes (27%), HIV (7%) and glomerulonephritis (8%). Complaints were related to infection (18%), dyspnea (17%), vascular access (16%). chest pain or dysrhythmia (15%) and gastrointestinal complaints (12%). ED evaluation included CBC (79%), electrolytes (75%), CXR (57%) and EKG (48%). Antibiotics were administered to 21%. HD was performed earlier than scheduled in 14%. Two hundred and eighteen patients (62%) were admitted (ICU 11%, telemetry 22%), 19 (5%) refused admission and 2 expired in the ED. The average hospital length of stay was 7.8 days (range 1-59), with 29% hospitalized more than 1 week, compared to 6.54 days for non-HD patients. The mean facility charge for admitted subjects was $14,758, while the average cost for non-HD admissions was $7,152. Of the 133 patients (38%) who were discharged directly from the ED, the mean length stay was 223 minutes (range 30 to 750) and the mean charge was $658. The mean length of stay for non-HD patients was 124 minutes. CONCLUSION: The ED evaluation of adult HD patients involves multiple diagnostic modalities, and patients are usually admitted. The admit rate, ED length of stay for discharged patients and hospital charges for care were substantially higher in the HD patients than in the general population. Further research in the ED care of these complex patients should be undertaken.

Home antipyretic use in children brought to the emergency department.

OBJECTIVE: To determine how often children with a complaint of fever receive antipyretics at home and if any demographic factors are associated with correct dosing. METHODS: A prospective, descriptive study of children 3 to 36 months old presenting with complaint of fever was conducted. Caregivers were questioned about demographics and antipyretic given. The ability of demographics to predict proper dosing was tested first individually and then with a regression model. The effect of proper home dosing on presence of fever and height of fever was also analyzed. A total of 138 children were analyzed. RESULTS: Of the 118 (86%) who received antipyretics at home, only 47% had been given a proper dose. No demographic variable predicted proper dosing. CONCLUSION: Reported antipyretic dose at home did not predict presence of fever or height of temperature measured in the emergency department.

Accuracy of estimation of external blood loss by EMS personnel.

BACKGROUND: Emergency Medical Services (EMS) personnel provide care in the out-of-hospital setting. The EMS report, including blood volume estimates, influences hospital management. Our objective was to assess the accuracy of EMS blood volume estimates. METHODS: In this prospective, observational study, EMS providers were asked to view four simulated blood loss scenarios in random order. Each scenario used a specific volume of spilled blood corresponding to the loss likely to cause the four classes of hemorrhagic shock. Estimates are reported using median and interquartile ranges. RESULTS: Ninety-two EMS providers gave 368 estimates. Only 8% were within 20% of the actual volume. Furthermore, only 24% were within 50% of actual volume. There was no correlation between accuracy and any demographic variable, level of training, or years of EMS experience. CONCLUSION: EMS personnel are unable to estimate "blood" volume accurately irrespective of level of training.

Safe out-of-hospital treatment of chest pain without direct medical control.

INTRODUCTION: The use of direct medical control (DMC) in the out-of-hospital setting often is beneficial, but has the disadvantage of consuming emergency medical services (EMS) resources. HYPOTHESIS: Uncomplicated, nontrauma, adult patients with chest pain can be treated safely and transported by paramedics without DMC. METHODS: Retrospective chart review of all nontrauma, adult patients with chest pain treated in a combined rural and suburban EMS system during a 2-year period (December 1990 through November 1992) was conducted. Before November 1991, DMC was mandatory for all patients with chest pain. Beginning 01 November 1991, if a patient had resolution of a pain either spontaneously, with administration of oxygen, or after a single dose of nitroglycerin, DMC was at the discretion of the paramedic. Using the above criteria for inclusion, three study groups were defined: Group 1, before protocol change; Group 2, after protocol change without DMC; and Group 3, after protocol change when physician contact was obtained, but not required. These groups were compared for the following parameters: 1) scene time; 2) time to administration of first dose of nitroglycerin; 3) time interval between measurement of vital signs; 4) oxygen use; 5) intravenous access; and 6) electrocardiographic monitoring. Continuous and categorical variables were analyzed by multivariate and univariate analysis of variance and chi-square tests, respectively. RESULTS: Of 308 nontrauma, adult patients with chest pain, 71 met inclusion criteria in Group 1, 40 in Group 2, and 34 in Group 3. No statistically significant differences were identified in any of the study parameters. CONCLUSION: Adult patients with chest pain who have no other symptoms or complicating conditions can be treated appropriately be paramedics without DMC.

Secondary arterioenteric fistula involving the sigmoid colon.

An arterioenteric fistula is a life-threatening condition. Whereas most arterioenteric fistulae involve the duodenum, they can occur at any point along the gastrointestinal tract, and those to the lower tract may present with less classic symptoms than arterioduodenal fistulae. It is likely that more patients with arterioenteric fistulae will present to the emergency department (ED) in the future because of an increasing number of elective aortic aneurysm repairs in an aging population. We present a patient with a secondary fistula involving the sigmoid colon who presented to the ED with abdominal pain and a tender abdominal mass.

Complete heart block in a child with varicella.

A case of varicella myocarditis in a previously healthy 6-year-old child was reviewed. The patient presented with third-degree heart block and shock as the sole manifestation of her cardiac involvement. Bradyarrhythmias required temporary transvenous pacing. Intravenous acyclovir was used. The patient recovered without permanent sequelae. The natural history, clinical presentation, and treatment of varicella myocarditis are reviewed.