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Biomedical subjects

R J Lewis

Publications and source records attributed to R J Lewis.

At least 127 records · Page 7Linked to original sources

Emergency medicine and the development of the Food and Drug Administration's final rule on informed consent and waiver of informed consent in emergency research circumstances.

This article reviews the federal regulations for emergency and acute resuscitation research in effect prior to October 1996, the historical issues that contributed to the development of these regulations, the controversies that arose surrounding the application of these regulations to emergency research circumstances, and the methods by which the regulations were changed. The new regulations introduced by the U.S. Food and Drug Administration (FDA) also are reviewed.

Disclosure↗

Out-of-hospital intravenous access: unnecessary procedures and excessive cost.

OBJECTIVE: To evaluate the concordance with criteria developed by the study investigators and supply costs associated with placement of i.v. lines and saline locks by paramedics in the out-of-hospital setting. METHODS: This was a retrospective consecutive case series at an urban base hospital. Patients were treated by paramedics using one base hospital for medical control during December 1995. Base hospital written records and taped patient calls were reviewed to determine actual i.v. access method used by paramedics, chief complaint, and whether fluid administration was ordered. Indicated method of i.v. access was determined for each patient based on predetermined criteria developed by the investigators. i.v. access methods were ranked by cost of supplies as follows: i.v. line (i.v.) > saline lock (SL) > no i.v. line (No i.v.). An assignment of concordant treatment was made when actual = indicated method, discordant-overtreatment when actual > indicated, and discordant-undertreatment when actual < indicated. RESULTS: 452 patients were treated via radio by the base hospital during the study period. 380 of 452 (84%) received an i.v.. 28 of 380 (7%) received fluid resuscitation in the field. 166 of 452 (37%) received concordant treatment; 253 (56%) discordant-overtreatment; and 33 (7%) discordant-undertreatment. Pediatric patients (< or =14 years of age) were more likely to be undertreated as compared with adults, 33% vs 3% (p < 0.001). Patients who had medical chief complaints were more likely to receive discordant-overtreatment as compared with patients who had trauma chief complaints, 61% vs 32% (p < 0.001). 73% of chest pain patients received discordant-overtreatment. Based on these data, the yearly cost of supplies used in i.v. access discordant-overtreatment was $13,735 for this base hospital and $560,000 for the Los Angeles County emergency medical services (EMS) system. 91% of the excess supply cost is due to patients' receiving an i.v. instead of a SL. CONCLUSION: Based on study criteria for utilization of i.v. lines vs SLs in the field, paramedics and base hospital personnel often provide discordant-overtreatment of patients by placement of an i.v. when a SL or No i.v. would suffice, resulting in unnecessary costs for EMS systems.

Adolescent↗

Research fundamentals: I. Getting from hypothesis to manuscript: an overview of the skills required for success in research.

This is the first in a series of articles developed by members of the Society for Academic Emergency Medicine (SAEM) Research Committee. The purpose of this series is to describe a stepwise approach to research, from the inception of a hypothesis to the final publication of a report. This series is written for junior academic emergency physicians (EPs), as well as nonacademic physicians who have an interest in research. This first article presents an overview of the steps involved in performing research and publishing the results, emphasizing the initial steps and the importance of collaboration.

Data Interpretation, Statistical↗

Gallstone pancreatitis: a prospective study on the incidence of cholangitis and clinical predictors of retained common bile duct stones.

OBJECTIVE: The aim of this study was to define the incidence of cholangitis in gallstone pancreatitis, in the absence of cholangitis, to identify the clinical predictors of persistent common bile duct (CBD) stones at endoscopic retrograde cholangiography (ERCP) or at intraoperative cholangiography (IOC). METHODS: A total of 122 consecutive patients with acute gallstone pancreatitis were prospectively evaluated for the presence of CBD stones as determined by elective ERCP or IOC. Urgent ERCP was restricted to patients with concomitant cholangitis. APACHE II scores and serial laboratory data were obtained. RESULTS: Four (3%) patients had cholangitis and all underwent urgent ERCP successfully. Eighteen (15%) patients without cholangiogram were excluded. The remaining 100 patients underwent elective ERCP or IOC on a mean of hospital day 6.8. Twenty-one (21%) patients had persistent CBD stones. Univariate analysis detected significant differences in serum total bilirubin, ALT, and alkaline phosphatase levels between patients with and without persistent CBD stones. On multivariate analysis, serum total bilirubin on hospital day 2 was the best predictor of CBD stones. A serum total bilirubin level > 1.35 mg/dl had a sensitivity of 90.5% and specificity of 63%. Age, gender, mean APACHE II score, amylase, and presence of CBD dilation on ultrasound were not predictive of CBD stones. CONCLUSION: In patients with gallstone pancreatitis, 1) cholangitis is uncommon, and 2) the best clinical predictor of persistent CBD stones is serum total bilirubin on hospital day 2.

APACHE↗

Solution structure and proposed binding mechanism of a novel potassium channel toxin kappa-conotoxin PVIIA.

BACKGROUND: kappa-PVIIA is a 27-residue polypeptide isolated from the venom of Conus purpurascens and is the first member of a new class of conotoxins that block potassium channels. By comparison to other ion channels of eukaryotic cell membranes, voltage-sensitive potassium channels are relatively simple and methodology has been developed for mapping their interactions with small-peptide toxins. PVIIA, therefore, is a valuable new probe of potassium channel structure. This study of the solution structure and mode of channel binding of PVIIA forms the basis for mapping the interacting residues at the conotoxin-ion channel interface. RESULTS: The three-dimensional structure of PVIIA resembles the triple-stranded beta sheet/cystine-knot motif formed by a number of toxic and inhibitory peptides. Subtle structural differences, predominantly in loops 2 and 4, are observed between PVIIA and other conotoxins with similar structural frameworks, however. Electrophysiological binding data suggest that PVIIA blocks channel currents by binding in a voltage-sensitive manner to the external vestibule and occluding the pore. Comparison of the electrostatic surface of PVIIA with that of the well-characterised potassium channel blocker charybdotoxin suggests a likely binding orientation for PVIIA. CONCLUSIONS: Although the structure of PVIIA is considerably different to that of the alphaK scorpion toxins, it has a similar mechanism of channel blockade. On the basis of a comparison of the structures of PVIIA and charybdotoxin, we suggest that Lys19 of PVIIA is the residue which is responsible for physically occluding the pore of the potassium channel.

Amino Acid Sequence↗

Oligosaccharide specificity of a family 7 endoglucanase: insertion of potential sugar-binding subsites.

Family 7 of the glycosyl hydrolases contains both endoglucanases and cellobiohydrolases. In addition to their different catalytic activities on crystalline substrates, the cellobiohydrolases differ from the endoglucanases in their activity on longer soluble substrates, indicative of a greater number of subsites on the enzyme. A double mutant (S37W, P39W) of the Humicola insolens endoglucanase I (EG I) has been constructed in order to mimic aspects of the subsite structure of the corresponding family 7 cellobiohydrolase, cellobiohydrolase-I (CBH I). The 3-D crystal structure of the double mutant has been solved and refined to a crystallographic R-factor of 0.17 at a resolution of 2.2 A (1 A = 0.1 nm). The two mutant tryptophans are clearly visible in the electron density and are in the same orientation as those found in the substrate binding groove of CBH I. In addition to the substitutions, the C-terminal amino acids (399QELQ), disordered in the native enzyme structure, are clearly visible and there are a small number of minor loop movements associated with differences in crystal packing. Kinetic determinations show that the S37W, P39W mutant EG I has almost identical activity, compared to native EG I, on small soluble cellodextrins. On phosphoric acid swollen cellulose there is a small (30%), but significant, decrease in the apparent KM indicating that the double mutant may indeed exhibit stronger binding to longer polymeric substrates.

Binding Sites↗

A Queensland family with ciguatera after eating coral trout.

Ciguatera (poisoning caused by eating fish contaminated with algal toxins) is usually diagnosed clinically. We describe a Queensland family of four (including a pregnant woman) with ciguatera, confirmed by bioassay of the implicated fish for ciguatoxin. All four recovered, illustrating the effectiveness of treatment with intravenous mannitol. At birth, the infant appeared to suffer no adverse effects attributable to ciguatera; to our knowledge, this is the first report of the effect of severe ciguatera in the first trimester of pregnancy.

Adult↗

Determination of the solution structures of conantokin-G and conantokin-T by CD and NMR spectroscopy.

Conantokin-G and conantokin-T are two paralytic polypeptide toxins originally isolated from the venom of the fish-hunting cone snails of the genus Conus. Conantokin-G and conantokin-T are the only naturally occurring peptidic compounds which possess N-methyl-D-aspartate receptor antagonist activity, produced by a selective non-competitive antagonism of polyamine responses. They are also structurally unusual in that they contain a disproportionately large number of acid labile post-translational gamma-carboxyglutamic acid (Gla) residues. Although no precise structural information has previously been published for these peptides, early spectroscopic measurements have indicated that both conantokin-G and conantokin-T form alpha-helical structures, although there is some debate whether the presence of calcium ions is required for these peptides to adopt this fold. We now report a detailed structural study of synthetic conantokin-G and conantokin-T in a range of solution conditions using CD and 1H NMR spectroscopy. The three-dimensional structures of conantokin-T and conantokin-G were calculated from 1H NMR-derived distance and dihedral restraints. Both conantokins were found to contain a mixture of alpha- and 310 helix, that give rise to curved and straight helical conformers. Conantokin-G requires the presence of divalent cations (Zn2+, Ca2+, Cu2+, or Mg2+) to form a stable alpha-helix, while conantokin-T adopts a stable alpha-helical structure in aqueous conditions, in the presence or absence of divalent cations (Zn2+, Ca2+, Cu2+, or Mg2+).

Animals↗

Experience with intubated patients does not affect the accidental extubation rate in pediatric intensive care units and intensive care nurseries.

Accidental extubation is a potentially serious event for pediatric or neonatal patients with respiratory failure, especially in clinical settings in which personnel capable of performing reintubation may not be readily available. Thus the rate of accidental extubation in small intensive care units that operate without 24-hour in-house physician availability may be an important quality assurance indicator. The objective of this study were to determine the accidental extubation rate at a single small pediatric intensive care unit (PICU) and compare it with published reports. This study was carried out in a six-bed PICU at Washoe Medical Center in Reno, Nevada, with a relatively low level of patient acuity, as measured by PRISM score and the frequency of intubation, and without 24-hour in-house physician availability. All intubated patients admitted during the 5-year period from January 1, 1989 to December 31, 1993 were included. The primary outcome measure was the occurrence of accidental extubation. We observed only two accidental extubations in 1,749 intubated-patient-days (IPD) (0.114 accidental extubations/100 IPD [95% confidence interval 0.014-0.413 accidental extubations/ 100 IPD]). This rate of accidental extubation was compared with data in published reports from neonatal intensive care units (NICUs) and PICUs, which ranged from 0.14 accidental extubations/100 IPD to 4.36 accidental extubations/100 IPD. The dependence of the observed accidental extubation rate on unit size and institutional experience with intubated patients, as measured by the average number of intubated patients, was examined. We found no evidence that the accidental extubation rate is higher in smaller units or units with less institutional experience. Low rates can be achieved in small units with low acuity.

Adolescent↗

Pacific ciguatoxin-1 associated with a large common-source outbreak of ciguatera in east Arnhem Land, Australia.

We report a retrospective study of the clinical signs and symptoms associated with a point-source outbreak of fish poisoning that occurred with a fish captured from the Arafura Sea, northern Australia. Twenty cases (16 Aboriginal and 4 non-Aboriginal) characteristic of ciguatera, including 4 inpatients and 16 outpatients from the Gove Hospital, were identified based on the pattern of clinical symptoms and signs after ingestion of a large coral cod from a known ciguatera-prone coral reef. In the absence of a serologic test for the victim, laboratory analysis of a 230-g sample of the coral cod (Cephalopolis miniatus), using both mouse bioassay and HPLC/mass spectometry, showed that Pacific ciguatoxin-1 was the principal toxin involved. Intravenous mannitol was administered to one patient without clear benefit. Risk factors for ciguatera poisoning are ingestion of larger portions of reef fish from ciguatera-prone areas. Despite apparent local awareness of the distribution and etiology of the disease, large common-source outbreaks of ciguatera still occur.

Adult↗

Prejudice toward fat people: the development and validation of the antifat attitudes test.

Although the stigma of obesity in our society is well documented, the measurement of antifat attitudes has been a difficult undertaking. Two studies were conducted to construct and validate the Antifat Attitudes Test (AFAT). In study 1, college students (110 men and 175 women) completed the preliminary 54-item AFAT and specific indices of body image and weight-related concerns. Psychometric and factor analysis revealed a 47-item composite scale and three internally consistent factors that were uncorrelated with social desirability: Social/Character Disparagement, Physical/Romantic Unattractiveness, and Weight Control/Blame. Several body images correlates of antifat prejudice were identified, and men expressed more negative attitudes than women. Study 2 experimentally examined the effects of information about the controllability of weight on the antifat attitudes of 120 participants. Exposure to information on behavioral vs. biogenetic control led to greater blame of persons who are fat for their body size. The implications of the findings and the potential utility of the AFAT are discussed.

Adolescent↗

Asymptomatic carotid artery stenosis screening in patients with lower extremity atherosclerosis: a prospective study.

Eighty-nine male veterans presenting to a vascular surgery clinic with symptomatic lower extremity atherosclerosis were prospectively screened by duplex scan for asymptomatic carotid artery stenosis (CAS). Their chief complaint was: claudication (90%), rest pain (6%), and ischemic ulcer or gangrene (4%). The mean ankle-brachial index (ABI) was 0.77. Twenty-five CAS > 50% were detected in 18 (20%) patients. Twelve CAS > 75% were detected in 11 (12%) patients. There was no difference between patients with and without CAS > 50% with regards to mean ABI, history of angina, diabetes, hypertension, prior coronary artery bypass, or history of smoking. Carotid bruit was associated with ipsilateral CAS > 50% [p < 0.0001, sensitivity (52%), specificity (88%), positive predictive value (41%), negative predictive value (92%)]. As a result of the screening, eight elective carotid endarterectomies have been performed to date in six (7%) patients with one transient twelfth cranial nerve paresis as the only postoperative complication. We conclude that: (1) male patients presenting with symptomatic lower extremity atherosclerosis have a 20% prevalence of asymptomatic CAS > 50%, (2) there is no correlation between the degree of lower extremity ischemia and CAS > 50%, (3) carotid bruit is significantly associated with CAS > 50%, but has a low sensitivity, and (4) routine CAS screening should be considered for all male patients with symptomatic lower extremity atherosclerosis regardless of whether a bruit is present.

Aged↗

One hundred video-assisted thoracic surgical simultaneously stapled lobectomies without rib spreading.

BACKGROUND: This study was performed to evaluate and determine the validity and benefits of video-assisted thoracic surgical simultaneously stapled pulmonary lobectomy without rib spreading. METHODS: Between September 1992 and August 1995, 100 consecutive video-assisted thoracic surgical simultaneously stapled lobectomies without rib spreading were performed. RESULTS: Forty-five male and 55 female patients had 24 right upper, 8 right middle, 29 right lower, 24 left upper, 15 left lower lobectomies for 66 adenocarcinomas, 20 squamous cell carcinomas, 4 large cell carcinomas, 8 benign lesions, and 2 metastatic lesions. Seventy-six patients had negative nodes. Nine patients had positive nodes. Every bronchoscopy was visually and cytologically negative. Forty-nine cervical mediastinoscopies were negative. Operating time for the series averaged 90.3 minutes. Hospitalization averaged 3.5 days for the entire group, but was 2.6 days for the last 20 patients. Lesions ranged from 1.5 to 8 cm, averaging 3.4 cm. There was no surgical mortality, no hemorrhage, no transfusion, and no urgent conversion to an open procedure. No bronchial fistula, vascular fistula, or bronchovascular fistula has occurred. Complications included 6 air leaks, 2 cerebrovascular accidents, 1 infected chest tube site, 2 cases of pneumonitis, and 1 subcutaneous emphysema. CONCLUSIONS: Video-assisted thoracic surgical simultaneously stapled lobectomy without rib spreading is a safe operation that can be combined with lymph node sampling. At this early stage, therapeutic outcomes (survival) for resected neoplasms appear similar to results obtained from traditional open techniques.

Adenocarcinoma↗

Characterization of ciguatoxins and ciguatoxin congeners present in ciguateric fish by gradient reverse-phase high-performance liquid chromatography/mass spectrometry.

Reverse-phase high-performance liquid chromatography/mass spectrometry (HPLC/MS) was used to identify Pacific ciguatoxins (P-CTX) and P-CTX congeners present in a highly purified extract from the viscera of ciguateric moray eels (Lycodontis javanicus) collected in the central Pacific Ocean. Fourteen P-CTX or P-CTX congeners were identified with protonated molecular ions [M + H]+ m/z 1095.7 (two), 1111.6 (six) or 1127.7 (six), including dominant ions for P-CTX-1, -2 and -3. In addition to the protonated species, each of these ciguatoxins gave rise to prominent [M + NH4]+ and [M + Na]+ ions. The 11 new P-CTX congeners, not readily detected by mouse bioassay, were present in trace amounts (2-13% of P-CTX-2 levels) and identified as several oxidized P-CTX-1, -2 and -3, and a possible diasteriomer of P-CTX-1. Acetonitrile-water gradients buffered with 1 mM ammonium acetate improved the separation and detection of the minor ciguatoxins compared with an acetonitrile-water gradient modified with 0.1% TFA. Turbo-assisted HPLC/MS had sufficient sensitivity to detect P-CTX-1 in a crude extract from the flesh of an Australian ciguateric fish. Compounds with masses equivalent to other isolated ciguatoxins, including Caribbean-CTX-1, gambiertoxin-4A and P-CTX-3C, were not detected in these samples. HPLC/MS can readily identify multiple ciguatoxins accumulated by fish and has the potential to be used as a confirmatory analytical method for characterizing the low levels of ciguatoxins contaminating ciguateric fish.

Animals↗

Identification of Caribbean ciguatoxins as the cause of an outbreak of fish poisoning among U.S. soldiers in Haiti.

On 24 February 1995, six U.S. soldiers serving with the Multinational Force in Haiti became ill after eating a locally caught fish identified as the greater amberjack Seriola dumerili. The victims presented with nausea, vomiting, watery diarrhea and abdominal cramps 5-8 hr after consumption. Also present in some victims were numbness in the extremities or perioral region, bradycardia and scalp paresthesia. Patients were treated with i.v. hydration therapy and antiemetics. All recovered without sequelae over the course of 1-3 months. A portion of the cooked fish was obtained for analysis. A semipurified lipid extract was prepared according to standard methods and analyzed for the presence of Na+ channel site 5 binding activity using a brevetoxin receptor binding assay. By this assay, the fish sample contained the equivalent of approximately 20 ng Caribbean ciguatoxin/g flesh. The presence of the major Caribbean ciguatoxin (C-CTX-1) was confirmed by liquid chromatography-mass spectrometry. Using the receptor binding assay to monitor activity in TSK and PRP-1 column fractions, two minor toxins were detected in addition to C-CTX-1. One of these minor toxins was more polar, and the other less polar, than C-CTX-1. These data provide firm evidence that a family of C-CTX-1 is responsible for ciguatera in the Caribbean.

Adult↗

Isolation and characterisation of Caribbean ciguatoxins from the horse-eye jack (Caranx latus).

The toxins involved in ciguatera (fish poisoning) in the Caribbean Sea were isolated from Caranx latus, a pelagic fish often implicated in ciguatera in the Caribbean region, and purified by mouse bioassay directed fractionation. Five toxins were separated by reverse-phase high-performance liquid chromatography (HPLC). In order of increasing hydrophobicity, these toxins included a sleep-inducing fraction (< 1% of total toxicity), a major Caribbean ciguatoxin (C-CTX-1, 65% of toxicity), a minor Caribbean ciguatoxin (C-CTX-2, 13% of toxicity), a minor toxin (approximately 1% of toxicity) and a hydrophobic, fast-acting toxin (approximately 19% of toxicity). The i.p. injection into mice of each toxin induced signs typical of site-5 sodium channel activator toxins such as the Pacific ciguatoxins and brevetoxins. C-CTX-1 and C-CTX-2 were purified to homogeneity (LD50 = 3.6 and approximately 1 microgram/kg, respectively) and subjected to ion spray mass spectrometry. Both lost up to five H2O molecules and each had a [M+H]+ ion, m/z 1141.7, suggesting that C-CTX-1 and -2 are diastereomers that differ from the Pacific family of ciguatoxins. Turbo-assisted HPLC-mass spectrometry identified C-CTX-1, C-CTX-2 and three C-CTX-1-related compounds in an enriched fraction but no Pacific ciguatoxins were detected. The presence of different families of ciguatoxins in ciguateric fish from the Caribbean Sea and Pacific Ocean probably underlies the clinical differences in the ciguatera syndrome reported in these two regions. A Caribbean strain of the benthic dinoflagellate, Gambierdiscus toxicus, is suspected as source of these ciguatoxins. The extent to which these toxins are biotransformed as they pass through the marine food chain remains to be determined.

Animals↗