Guidelines for clinical investigator involvement in industry-sponsored clinical trials. SAEM Research Committee.
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Advisory Committees↗
Biomedical subjects
R J Lewis
Publications and source records attributed to R J Lewis.
Hospital admission and age.
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Adolescent↗
Crystallization of inhibitor complexes of an N-terminal 24 kDa fragment of the DNA gyrase B protein.
A 24 kDa N-terminal fragment of the Escherichia coli DNA gyrase B protein has been crystallized in the presence of novobiocin. One crystal form has been obtained that is orthorhombic, P2(1)2(1)2(1), with unit cell dimensions a = 40.3 A, b = 47.7 A, c = 111.9 A. The asymmetric unit of this crystal form contains one molecule (Vm = 2.24 A3/Da). Complete native data have been collected to 2.5 A resolution. This same protein fragment has also been crystallized in the presence of GR122222X, an inhibitor that is structurally related to cyclothialidine. These crystals also exhibit P2(1)2(1)2(1) symmetry but have unit cell dimensions of a = 68.8 A, b = 68.6 A, c = 48.6 A. The Vm value of this crystal form is 2.39 A3/Da, assuming one molecule in the asymmetric unit, and native data have been collected to 2.0 A resolution. Molecular replacement studies of both complexes are underway.
Binding Sites↗
Ionspray mass spectrometry of ciguatoxin-1, maitotoxin-2 and -3, and related marine polyether toxins.
A range of marine polyether toxins from dinoflagellates were analysed by ionspray mass spectrometry. Ciguatoxin-1 ([M+H]+ m/z = 1,111.8) purified from several fish species yielded singly charged ions corresponding to the parent ion, sodium and H2O adducts and ions for the loss of up to five H2O molecules. Ciguatoxin-1 was detected to 1 ng; however, interference from fish lipids precluded direct detection of ciguatoxin-1 in crude extracts from fish flesh spiked with ciguatoxin-1 at a level equivalent to 1.5 ng ciguatoxin-1/g of extracted flesh. Maitotoxin-2 yielded doubly and triply charged ions for sodium and potassium salts and likely possessed only one sulphate ester (M(r) = 3,298 for the mono-sodium salt). Maitotoxin-3, a recently isolated small maitotoxin, yielded singly charged ions including ions for the loss of one sulphate and up to four H2O molecules. Maitotoxin-3 is proposed to be a polyether compound possessing two sulphate esters (M(r) = 1,060.5 for the disodium salt). Brevetoxin-A ([M+H]+ m/z = 867.5) and brevetoxin-B ([M+H]+ m/z = 895.5) yielded singly charged ions corresponding to the parent ion, Na+ adducts and the loss of up to four H2O molecules. Okadaic acid ([M+H]+ m/z = 805.5) yielded singly charged ions corresponding to the parent ion and ions for the loss of up to three H2O molecules. A signal for M + 18 Da species that may represent [M+NH4]+ was observed for ciguatoxin-1, brevetoxin-A and -B, and okadaic acid. For all polyethers examined, the orifice potential influenced the relative intensity of the ions detected in a predictable manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Purification and characterisation of large and small maitotoxins from cultured Gambierdiscus toxicus.
Three strains of cultured Gambierdiscus toxicus yielded distinct maitotoxins (maitotoxin-1, -2, and -3) which were purified to homogeneity by high pressure liquid chromatography. Maitotoxins-1 and -2 are large toxins (molecular weights for the sodium salts = 3,422 and 3,298, respectively), whereas maitotoxin-3 is relatively small (molecular weight = 1,060 for the sodium salt). The contractile actions on isolated guinea-pig left atria, vas deferens and ilea of maitotoxins-1 and -2 were compared with those of the small maitotoxin, maitotoxin-3. Maitotoxin-1, -2 and -3 each produced quantitatively similar, concentration-dependent patterns of positive and negative inotropy in atria when compared on a mouse unit/ml basis (one mouse unit is the intraperitoneal LD50 dose for a 20 g mouse; the LD50 for maitotoxin-2 = 0.08 microgram/kg). Concentrations of maitotoxin-2 greater than 5 x 10(-13) M caused positive inotropy. The three maitotoxins produced patterns of contractions in vas deferens and ilea that were qualitatively similar, including a period of prominent spike activity in vas deferens. On a mouse unit/ml basis, the order of potency on smooth muscle was maitotoxin-1 > maitotoxin-3 > maitotoxin-2. The contractile responses of smooth muscle to the maitotoxins were followed by an inhibitory phase where control agonist responses could not be elicited. The maitotoxin-induced contractile responses of vas deferens were inhibited by nicardipine but not phentolamine, indicating that in this tissue, each maitotoxin has mainly a direct contractile effect that requires calcium influx through voltage-sensitive calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The S-oxidative degradation of a novel corticosteroid tipredane (INN). Part II--Detailed investigations into the primary S-oxidation of tipredane using achiral oxidants.
The C-17 dithioketal moiety of the corticosteroid tipredane (INN,I) has been shown to undergo site and stereoselective S-oxidations with a range of achiral oxidants. S-Oxidation was favoured on the methylthio substitutent (beta-plane) in preference to the ethylthio substituent (alpha-plane) in a ratio of 1.8-3.5:1. S-Oxidation on both substituents appeared to be stereoselective yielding an approximate ratio of 4:1 and 1:3.5-6 for the S-:R-methyl and ethylsulphoxide diastereoisomers, (II and VI) respectively. The preferred sites for S-oxidation have been explained in terms of the preferred rotamers of the C-17 substituents and the steric factors imposed on the attack of the oxidant on the lone pair of electrons at each sulphur atom. Optimized HPLC conditions using a Hypersil ODS column and an acetonitrile-0.025 M NH4OAc pH 7.2 gradient at 26 degrees C were developed to prevent degradation of the ethylsulphoxide diastereoisomers (VI) occurring during chromatographic analysis, via elimination of ethylsulphenic acid to yield the corresponding C-17 vinylmethylthio derivative (VII).
Administration, Topical↗
The rapid potentiometric detection of catalase positive microorganisms.
The rate of fluoride ion release from the enzymatic cleavage of fluoride ion from 4-fluorophenol by horseradish peroxidase, in the presence of hydrogen peroxide, was measured using a fluoride ion selective electrode. Monitoring the utilisation of hydrogen peroxide by catalase (intracellularly present in almost all aerobic microorganisms) in the presence of 4-fluorophenol demonstrated the inhibition of the enzyme. Horseradish peroxidase appeared to impart a partial protective mechanism of this inhibition. The development of a sequential assay demonstrated the applicability of the proposed method in the assessment of aerobic microorganism numbers. The judicious variation of three parameters, the length of incubation, the concentration of the primary substrate (hydrogen peroxide) and the indicator enzyme activity (horseradish peroxidase), affected both the detection limit and the sensitivity of the assay. Typically with a 15 minute incubation, a detection limit for catalase activity of 1.5 x 10(-6) Uml-1 was obtained together with a sensitivity of 2.42 mumol l-1 s-1 per decade change in activity. Application of the developed catalase assay to the detection of Escherichia coli achieved a detection limit of 1 x 10(2) colony forming units (cfu) ml-1 with a sensitivity of 3.26 mumol l-1 s-1 per decade change in intact microorganisms. By lysis of the microorganisms the detection limit was further reduced to less than 10 cfu ml-1, indicating the future possibilities of the assay.
Bacteria, Aerobic↗
Patients who leave emergency departments without being seen by a physician: magnitude of the problem in Los Angeles County.
STUDY OBJECTIVES: To determine the hospital characteristics associated with patients leaving emergency departments prior to physician evaluation. DESIGN: Cross-sectional design with data collection by mail and telephone survey. SETTING: Los Angeles County, California. TYPE OF PARTICIPANTS: Convenience sample of four public and 26 private hospital EDs with a combined monthly volume of 92,570. INTERVENTIONS: None. RESULTS: Questionnaires were returned from 83% of EDs surveyed. During 1990, 4.2% of patients at these EDs left without being seen by a physician. In all, 7.3% of public hospital patients left without being seen, and 2.4% of private hospital patients left without being seen (P < .001). The percentage of patients who left without being seen was significantly higher at EDs with longer waiting times, higher fraction of uninsured patients, and at hospitals with accredited residency training programs (P < .001 for each comparison). A logistic regression model, used to simultaneously evaluate the effects of multiple correlated factors, revealed that waiting time, fraction of patients uninsured, and teaching status had independent positive associations with patients who left without being seen. CONCLUSION: More than 4% of patients who seek care at EDs in Los Angeles County leave without being seen by a physician. A greater proportion of patients leave without medical evaluation from EDs with long waiting times for ambulatory patients and from those that serve uninsured populations. These findings should be interpreted in light of existing data on the health consequences faced by patients who leave hospital EDs without treatment.
Adult↗
Adenosine for the prehospital treatment of paroxysmal supraventricular tachycardia.
STUDY OBJECTIVE: To determine the efficacy and feasibility of adenosine for the treatment of paroxysmal supraventricular tachycardia (PSVT) in the prehospital setting. DESIGN: Prospective case series. SETTING: Large, urban, advanced life support emergency medical services system. PARTICIPANTS: One hundred twenty-nine adult patients with PSVT, as identified by paramedic personnel. Pregnant patients and those taking carbamazepine or dipyridamole were excluded. INTERVENTIONS: Dose of 12 mg adenosine by rapid i.v. push followed by a 5-mL saline flush and a repeat dose of 12 mg adenosine i.v. push if the patient's rhythm remained unchanged. MEASUREMENTS AND MAIN RESULTS: Six-second lead II rhythm strips and vital signs were documented before and 2 minutes after the administration of adenosine. Demographic information, past medical history, medications, number of adenosine doses given, and complications were recorded by the paramedic on a case-report form. One hundred six of 129 (82%) of the case-report forms included the rhythm strips from before and after adenosine administration. Actual initial rhythms were determined by a consensus panel. The initial rhythms were PSVT in 79% (84 of 106) of patients, atrial fibrillation in 12% (13 of 106), sinus tachycardia in 5% (five of 106), atrial flutter in 2% (two of 106), and ventricular tachycardia in 2% (two of 106). Eighty-five percent (71 of 84) of patients in PSVT were successfully converted to sinus rhythms; four (5.6%) of these patients required a second 12-mg dose. One patient in atrial fibrillation spontaneously converted to normal sinus rhythm and one patient in ventricular tachycardia converted after adenosine. All other patients not initially in PSVT remained in their initial rhythm. Complications occurred in 12 of 129 patients and included chest pain (five), flushing (three), shortness of breath (two), nausea (one), anxiety (one), dizziness (one), headache (one), and seizure (one). All complications were transient and required no treatment. Prior history of PSVT was the only variable associated with a higher rate of conversion (P = .029). CONCLUSION: Paramedics are able to accurately identify PSVT using a single lead. Adenosine is safe and effective treatment for PSVT in the prehospital setting. This series is the largest prehospital study of adenosine use to date.
Adenosine↗
Exposure of emergency department personnel to tuberculosis: PPD testing during an epidemic in the community.
STUDY OBJECTIVE: The present epidemic of tuberculosis has increased the risk of transmission of tuberculosis to health care workers in general and emergency department staff in particular, who often treat patients with tuberculosis before their diagnosis. The purpose of this study was to determine the risk of tuberculosis exposure among the nursing and physician staff of an urban ED. DESIGN: Observational study of self-reported purified protein derivative (PPD) skin test results and tuberculosis exposure. SETTING: Urban, public ED. PARTICIPANTS: Attending physicians, resident physicians, and registered nurses. INTERVENTIONS: None. RESULTS: Questionnaires were sent to all attending physicians, resident physicians, and registered nurses in the ED at Harbor-UCLA Medical Center requesting information on the subject's present and prior PPD status, known exposure to tuberculosis, and duration of time and average number of hours worked in the ED. Ninety-six of 129 questionnaires (74%) were returned. Five of the respondents had been immunized with Bacillus of Calmette and Guerin vaccine (BCG) and 10 of the respondents were PPD positive before beginning work in the ED. Of the other 81 respondents, 31% (25 of 81) had become PPD positive while working in the ED. The majority of these conversions (15 of 25) occurred in the first 6 months of 1993. A Kaplan-Meier survival analysis revealed nearly a 40% risk of PPD conversion after 60 months of full-time work in the ED. CONCLUSION: As measured by self-reported PPD status, a high rate of exposure to tuberculosis has been observed among the ED staff at Harbor-UCLA Medical Center. The highest rate of PPD conversion has been noted most recently, suggesting that there has been a significant increase in staff exposure to tuberculosis during 1992 and the beginning of 1993. Systematic monitoring of PPD conversion rates among ED staff is necessary to determine the adequacy of ED respiratory isolation procedures during the current tuberculosis epidemic.
California↗
Determining the need for admission in patients with new-onset seizures.
STUDY OBJECTIVES: To determine which adult patients with new-onset seizures require admission and whether those who require admission can be identified in the emergency department. DESIGN: Retrospective chart review of patients seen during a 5-year period. SETTING: Urban county teaching hospital in southern California. PARTICIPANTS: Three hundred thirty-three adult patients with new-onset seizures. Patients were excluded if they had acute head trauma, hypoglycemia from diabetic therapy, or alcohol- or recreational drug-related seizures. INTERVENTIONS: Standardized medical evaluation including physical examination, CBC, SMA-7 (electrolytes, blood urea nitrogen, creatinine, glucose), calcium, cranial computed tomography (CT), lumbar puncture if indicated, and admission to the hospital. RESULTS: Forty-six percent of patients (136 of 294) admitted to our hospital required admission as judged by a retrospective evaluation of the ED and hospital course. The numbers of patients who had a clinically significant result with each part of the evaluation were: physical examination, 75 of 333 (23%); CBC, 25 of 319 (8%); SMA-7, 21 of 329 (6%); calcium, 2 of 208 (1%); CT, 134 of 325 (41%); and lumbar puncture, 19 of 227 (8%). Ninety-five percent of patients requiring admission (129 of 136) were detected by the standardized medical evaluation. CONCLUSION: One half of patients with new-onset seizures require admission. Patients with new-onset seizures who require admission can usually be detected by a standardized medical evaluation in the ED.
Adolescent↗
Prospective evaluation of emergency department medical clearance.
STUDY OBJECTIVE: To analyze a standardized medical evaluation of alert, adult emergency department patients with new psychiatric symptoms. DESIGN: Prospective, descriptive case series. SETTING: Urban, county hospital. PARTICIPANTS: One hundred consecutive, alert patients, aged 16 to 65 years, seen over 9 months, with new psychiatric symptoms. Excluded patients included those with obvious alcohol or drug intoxication, psychiatric patients with previously diagnosed abnormal behavior, psychiatric patients with medical complaints, and overdose or suicide patients. INTERVENTIONS: The following evaluation was performed: medical history, physical examination, complete blood count, SMA-7 (electrolytes, blood urea nitrogen, creatinine, and glucose), prothrombin time, calcium, oxygen saturation, creatine phosphokinase (CPK) if there was possible myoglobulinuria, alcohol level, urine drug screen (for cocaine, amphetamine, and phencyclidine), cranial computed tomography, lumbar puncture if febrile, and psychiatric evaluation when appropriate. Results were considered significant when they diagnosed the cause of the symptoms or resulted in medical admission. RESULTS: Sixty-three of the 100 patients had an organic etiology of their symptoms. The medical history was significant in 27, physical examination in 6, CBC in 5, SMA-7 in 10, CPK in 6, alcohol and drug screen in 28, computed tomography scan in 8, and lumbar puncture in 3. CONCLUSION: Most alert, adult patients with new psychiatric symptoms have an organic etiology. We recommend performing a medical history, physical examination, SMA-7, calcium, CPK if there is possible myoglobinuria, alcohol and drug screens, computed tomography scan, and lumbar puncture as part of the medical clearance of these patients.
Adolescent↗
Colorectal polyp incidence among polypropylene manufacturing workers.
To follow up earlier findings of increased colorectal cancer and polyp risk among a group of Texas polypropylene manufacturing workers, a second company-sponsored colorectal cancer screening program was conducted. Ninety-four (64%) of the 147 male workers negative for polyps in the first screening were rescreened. Age- and examiner-adjusted incidence rate ratios (IRRs) were modestly elevated for polypropylene manufacturing workers compared with patients screened at the same clinic for total (IRR = 1.31; 90% confidence interval [CI] = 0.84 to 2.03) and adenomatous (IRR = 1.80; 90% CI = 0.68 to 4.78) polyps. However, risk of adenomas among the highest exposed group (early term process/mechanical workers: IRR = 1.77; 90% CI = 0.51 to 6.18) was similar to risk in the least-exposed group (engineer/chemist/administrative workers: IRR = 2.02; 90% CI = 0.56 to 7.31). The modest, nonsignificant excesses and the similarity in risk across job categories does not suggest an occupationally related risk, although small numbers and potential biases preclude making definitive conclusions.
Adenocarcinoma↗
Parental recall after a visit to the emergency department.
Using exit interviews, we determined parental recall of their child's diagnosis, treatment, and follow-up instructions after a visit to the emergency department (ED). Over 2 weeks, 159 parents were interviewed. Exclusion criteria were: parental language other than Spanish or English, admission, trauma, child abuse, or a primary psychiatric diagnosis. Neither language nor parental satisfaction with communication (reported in 93%) was associated with ability to state the diagnosis correctly (P = NS). Seventy-five percent (88 of 117) of parents of children given a single diagnosis stated it correctly; 55% (23 of 42) of parents of children given multiple diagnoses were able to correctly state them all (P = 0.013). If a single medication was prescribed, 30% (20 of 67) of parents knew its name, while only 13% (four of 31) knew all names of multiple medications (P = 0.070). Of those parents given a single medication, 51% (34 of 67) knew how to administer it, while only 10% (three of 31) knew how to administer multiple medications (P < 0.001). Similarly, 58% (46 of 79) of parents given a single appointment knew the date and place of their child's follow-up, while only 16% (three of 19) given multiple appointments knew all dates and locations (P = 0.001). These data suggest that despite high parental satisfaction with communication, many parents cannot fully recall their child's diagnosis, treatment, and follow-up--especially when multiple diagnoses, medications, or appointments are given.
Adult↗
The effects of bundling on infant temperature.
OBJECTIVE: To determine whether bundling elevates rectal and/or skin temperature of young infants. DESIGN: Randomized, prospective study stratified by age. SETTING: Clinical Studies Center at a teaching hospital in Los Angeles. PATIENTS: Sixty-four well, full-term infants (ages 11 to 95 days). INTERVENTIONS: Control infants (n = 28) were dressed in a disposable diaper and terry coveralls. Bundled infants (n = 36) were dressed as control infants, plus a cap, a receiving blanket, and a thermal blanket. All infants were monitored in an open crib (room temperature 72 degrees to 75 degrees F). Rectal and skin (anterior mid-lower leg) temperatures and infant states were measured at 5-minute intervals from time 0 to 60 minutes and at 62 and 65 minutes. RESULTS: The mean skin temperature of bundled infants increased by 2.67 degrees C/hr; mean rectal temperature increased by 0.06 degrees C/hr. The mean skin temperature of nonbundled infants increased by 1.5 degrees C/hr; mean rectal temperature decreased by less than 0.01 degree C/hr. Comparing bundled infants to nonbundled controls, there was a significant rise in skin temperature (P = .0001) but not in rectal temperature (P > .05, Wilcoxon rank sum test). The study had a power > 98% to detect a rise of .5 degrees C in rectal temperature over 60 minutes. The 95% confidence interval for the change in rectal temperature in bundled infants was -0.03 to +0.15 degrees C. CONCLUSIONS: Bundling a healthy infant in a temperate external environment causes an increase in skin temperature, but not in rectal temperature. Elevated rectal temperatures should therefore, rarely if every be attributed to bundling.
Body Temperature↗
Colorectal cancer incidence among polypropylene manufacturing workers. An update.
This study updates an earlier investigation that found a sixfold excess incidence of colorectal cancer among polypropylene workers for the period January 1960 to September 1985. The study cohort comprised 412 male workers with at least 6 months employment and 10 years latency. For the extended follow-up period (October 1985 to May 1992), the standardized incidence ratio (SIR) based on state comparison rates was slightly elevated and not statistically significant (SIR = 1.5, 95% confidence interval [CI] = 0.5 to 3.5). A 2.3-fold excess was observed among process workers (95% CI = 0.3 to 8.2), but this was based on only two cases. Risk among process/mechanical workers was greater for short-term workers (< 10 years, SIR = 3.2, 95% CI = 0.7 to 9.2) compared with longer-term workers (> or = 10 years, SIR = 0.7, 95% CI = 0.02 to 4.0). Overall, the update findings do not suggest an occupationally related risk. Possible influences of company-sponsored colorectal cancer screening, the polyolefin unit shutdown, and other factors are discussed.
Aged↗
The role of video-assisted thoracic surgery for carcinoma of the lung: wedge resection to lobectomy by simultaneous individual stapling.
Despite a plethora of technologic advances, there has been only minimal improvement in the surgical treatment of carcinoma of the lung during the past 15 years. The advent of video-assisted thoracic surgical (VATS) techniques, however, is opening up new vistas and providing unimagined options for more accurate diagnosis, more precise staging, and more specific resections of lung tumors. Currently, a voluminous surgical literature supports tissue conservation, in selected patients, for the curative resection of peripheral malignant nodules less than 2 cm in diameter. Because these lesions are very accessible to a VATS resection, such procedures can be satisfactorily performed to meet the individual needs of the patient (ie, wedge, subsegmental, segmental, and sublobar resections, as well as traditional or SIS-lobectomy [simultaneous individual stapling of hilar structures]). As the technology advances, members of other specialties are beginning to develop a keen interest in the treatment of carcinoma of the lung. If thoracic surgeons are to prevail in the treatment of carcinoma of the lung, for the benefit of their patients, they must remain vigilant, informed, and versatile in their approach to this disease. This involves learning, understanding, and incorporating these new technologic advances into their armamentarium.
Humans↗