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R J Lewis

Publications and source records attributed to R J Lewis.

At least 145 records · Page 8Linked to original sources
PubMed1997

What is confidence? Part 1: The use and interpretation of confidence intervals.

Hypothesis testing and the P value it generates are overemphasized in statistical analyses published in medical journals. An alternative, the confidence interval (CI), offers significantly more information to readers interpreting results. There have been many authoritative calls for the report of CIs in place of P values, such as that of the International Committee of Medical Journal Editors, whose guidelines for statistical reporting give the following instructions: "When possible, quantify findings and present them with appropriate indicators of measurement error or uncertainty (such as confidence intervals)," and "Avoid sole reliance on statistical hypothesis testing, such as the use of P values, which fails to convey important quantitative information." In this article, part 1, we provide an overview of CIs for the clinician reading the medical literature. We describe the advantages of CIs and explain and illustrate their proper interpretation. In part 2, which follows this article, we provide added information important for clinical researchers, including a precise definition of CIs, a compact reference to methods for calculating CIs in common situations, and an explanation of the difference between CIs and probability intervals.

Biometry↗
PubMed1997

What is confidence? Part 2: Detailed definition and determination of confidence intervals.

In many cases, CIs should be reported in place of P values. The lower limit of a 95% CI is chosen such that the probability of obtaining the value observed in the trial or a greater value is .025 and the upper limit such that the probability of obtaining the value observed or a lesser value is also .025. CIs for data from most clinical trials may be calculated easily with the use of formulas given in this article. A 95% CI is not the same as a 95% probability interval. The 95% CI contains values statistically consistent with the data obtained, whereas a 95% probability interval has a 95% probability of containing the true value of interest.

Confidence Intervals↗
PubMed1996

A consensus structure for omega-conotoxins with different selectivities for voltage-sensitive calcium channel subtypes: comparison of MVIIA, SVIB and SNX-202.

The omega-conotoxins are a set of structurally related peptides that have a wide range of specificities for different subtypes of the voltage-sensitive calcium channel (VSCC). To understand their VSCC subtype differentiation we studied the structure of two naturally occurring omega-conotoxins, MVIIA (specific to N-type) and SVIB (specific to P/Q-type) and a synthetic hybrid, SNX-202, which has altered specificities to both VSCC subtypes. The secondary structures of the three peptides are almost identical, consisting of a triple-stranded beta-sheet and several turns. A comparison of NMR data emphasizes the structural similarities between the peptides and highlights some minor structural differences. In the three-dimensional structures of SVIB and MVIIA these are manifested as orientational differences between two key loops. The structural rigidity of MVIIA was also examined. H alpha shifts are similar in a range of solvents, indicating that there are no solvent-induced changes in structure. The omega-conotoxins form a consensus structure despite differences in sequence and VSCC subtype specificity. This indicates that the omega-conotoxin macrosites for the N/P/Q-subfamily of VSCCs are related, with specificity for receptor targets being conferred by the positions of functional side-chains on the surface of the peptides.

Amino Acid Sequence↗
PubMed1996

The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystallography.

This study describes the first crystal structures of a complex between a DNA topoisomerase and a drug. We present the structures of a 24 kDa N-terminal fragment of the Escherichia coli DNA gyrase B protein in complexes with two different inhibitors of the ATPase activity of DNA gyrase, namely the coumarin antibiotic, novobiocin, and GR122222X, a member of the cyclothialidine family. These structures are compared with the crystal structure of the complex with an ATP analogue, adenylyl-beta-gamma-imidodiphosphate (ADPNP). The likely mechanism, by which mutant gyrase B proteins become resistant to inhibition by novobiocin are discussed in light of these comparisons. The three ligands are quite dissimilar in chemical structure and bind to the protein in very different ways, but their binding is competitive because of a small degree of overlap of their binding sites. These crystal structures consequently describe a chemically well characterized ligand binding surface and provide useful information to assist in the design of novel ligands.

Adenylyl Imidodiphosphate↗
PubMed1996

Ultrafast computed tomography as a diagnostic modality in the detection of coronary artery disease: a multicenter study.

BACKGROUND: Ultrafast computed tomography (CT), by acquiring images of the proximal coronary arteries, detects coronary calcifications and has been demonstrated to be highly sensitive for the detection of coronary artery disease in many small studies. The aim of this study was to determine the relationship between ultrafast CT scanning and coronary angiography in a large number of symptomatic patients. METHODS AND RESULTS: The study population consisted of 710 patients from six participating centers. A multivariate logistic regression model was used to evaluate the individual contributions of age, number of calcified vessels, and the calcium score for the probability of angiographically significant disease. Of the 710 patients enrolled, 427 patients had significant angiographic disease, and coronary calcification was detected in 404, yielding a sensitivity of 95%. Of the 23 patients without calcifications, 19 (83%) had single-vessel disease at angiography. Of the 283 patients without angiographically significant disease, 124 had negative ultrafast CT coronary studies, for a specificity of 44%. An increasing number of vessels with calcification present on ultrafast CT was found to increase specificity for the presence of obstructive coronary artery disease in at least one vessel (P < .0001). As the log of the calcium score increases, the probability of multivessel obstructive disease increases (P < .0001). CONCLUSIONS: Ultrafast CT scanning is an noninvasive, non-exercise-dependent test with an excellent sensitivity for the detection of coronary artery disease. The presence of calcifications in multiple vessels and in younger populations correlates with higher specificities for obstructive disease, making ultrafast CT coronary scanning a very useful diagnostic test.

Adult↗
PubMed1996

Crystallisation of the Bacillus subtilis sporulation inhibitor SinR, complexed with its antagonist, SinI.

The transcription factor SinR, a pleiotropic regulator of late growth processes in Bacillus subtilis, has been crystallised as a complex with its antagonist SinI, in a form suitable for structural analysis. The SinI:SinR crystals diffract X-rays generated from a rotating copper anode source to 2.3 A spacing and a complete native dataset has been collected to this resolution limit. The space group of the crystals is P3(1)21 (or its enantiomorph P3(2)21) with cell dimensions a = b = 60.76 A, c = 87.79 A. Assuming that there is a single SinI:SinR heterodimer in the asymmetric unit, the crystals have a Vm of 2.53 A3.Da-1.

Bacillus subtilis↗
PubMed1996

Molecular mechanisms of drug inhibition of DNA gyrase.

DNA gyrase, an enzyme unique to prokaryotes, has been implicated in almost all processes that involve DNA. Although efficient inhibitors of this protein have been known for more than 20 years, none of them have enjoyed prolonged pharmaceutical success. It is only recently that the mechanisms of inhibition for some of these classes of drugs have been established unequivocally by X-ray crystallography. It is hoped that this detailed structural information will assist the design of novel, effective inhibitors of DNA gyrase.

4-Quinolones↗
PubMed1996

Cardiac assessment prior to vascular surgery: is dipyridamole-sestamibi necessary?

Dipyridamole-sestamibi (PMIBI) is recommended prior to vascular surgery in patients with > or = 1 Eagle criteria (Q waves, history of ventricular ectopy, diabetes, advanced age, and/or angina). To review our cardiac morbidity and mortality and the need for preoperative PMIBI, we reviewed 109 consecutive patients with a mean age of 59 years who underwent 145 elective major vascular procedures over a 1-year period. Seventy patients (with a mean of 0.8 Eagle criteria) underwent 92 vascular procedures without preoperative PMIBI and without coronary revascularization. Thirty-one patients (with a mean of 1.1 Eagle criteria) underwent 39 procedures without coronary revascularization following PMIBI, which showed reversible ischemia in seven and a fixed defect in 10; findings were normal in 14. Preoperative coronary bypass or angioplasty was limited to eight patients (14 procedures, mean of 1.6 Eagle criteria) who had unstable angina with (2 patients) or without (6 patients) acute myocardial infarction. There were four perioperative myocardial infarctions (2.8%), seven cardiac events overall (4.8%), and one cardiac death (0.7%). Three (43%) of the seven cardiac events occurred in patients with a normal scan or fixed defect on PMIBI imaging. In the absence of unstable angina, PMIBI had a sensitivity of only 25% and a specificity of 80% for cardiac events. We conclude that among patients without severe cardiac symptoms (1) PMIBI has a very limited ability to identify patients at risk for cardiac complications, and (2) preoperative PMIBI is neither necessary nor cost-effective.

Age Factors↗
PubMed1996

Primary varicella in adults: pneumonia, pregnancy, and hospital admission.

STUDY OBJECTIVE: To define the rate of complications of adult varicella, including pneumonia, and to determine the association of such complications with pregnancy. METHODS: Retrospective, descriptive case series of consecutive adult emergency department patients with primary varicella seen over a 31-month period in an urban county hospital. RESULTS: A total of 130 patients were identified, with a mean age of 23.9 +/- 6.1 years; 69 (53%) were female. Thirteen patients (10.0%) had pneumonia; 6 of these were hospitalized. Two patients admitted with pneumonia had significant underlying comorbid disease and expired from respiratory failure. The remaining 4 admitted patients recovered uneventfully. Four of the 7 patients discharged with pneumonia were known to have recovered uneventfully. Twenty-eight (41%) of the 69 female study patients were pregnant; 7 of these (25%) were admitted, with admission diagnoses of pneumonia (1), active labor (2), and pregnancy with varicella (4). Incidence of pneumonia in pregnant patients was 3.6% (1 of 28; 95% confidence interval, 1% to 18.3%). All 7 admitted pregnant patients and the 19 (of 21) discharged pregnant patients who were contacted recovered uneventfully. No congenital anomalies or perinatal complications were noted in the infants of the 26 mothers with documented follow-up. CONCLUSION: Hospital admission should be considered for adults with varicella pneumonia, especially if they have significant comorbid disease. It does not appear that pregnant women are at increased risk of developing varicella pneumonia.

Adolescent↗
PubMed1996

The S-oxidative degradation of a novel corticosteroid tipredane (INN) Part III. Detailed investigations into the disulphoxidation of tipredane.

The methyl- and ethylsulphoxide diastereoisomers (V and VI) of the corticosteroid tipredane (INN, I) have been shown to undergo further stereoselective S-oxidation to yield diastereoisomeric disulphoxides (II). Interactive computer optimisation software was employed to develop semi-preparative chromatography conditions for the isolation of the disulphoxide diastereoisomers (II) and to develop a multiselective gradient HPLC analysis of tipredane (I), the four monosulphoxide diastereoisomeric pairs (V, VI, IX and X), the four disulphoxide diastereoisomers (II), the vinyl methyl and ethyl derivatives (XI and XII) and the methylsulphone of tipredane (VII). The four diastereoisomeric disulphoxides (II) have been isolated by semi-preparative HPLC and their structures unambiguously confirmed by high resolution multinuclear NMR and mass spectrometry. The stereochemical assignment of the four disulphoxide diastereoisomers (II), the ethylsulphoxide diastereoisomeric pair (VI), and the vinyl methyl and ethylsulphoxide diastereoisomeric pairs (IX and X) was determined by degradation/synthesis and relation to the S/R-disulphoxide (II) whose stereochemistry was determined by X-ray crystallography. The monosulphoxides (V and VI) showed a high degree of site and stereoselectivity towards further S-oxidation. S-Oxidation on the C-17 beta-substituent of tipredane occurred at a rate approximately 50-fold faster than that on the alpha-substituent. The disulphoxides (II) have been shown to be susceptible to thermolysis yielding the vinyl methylsulphoxide diastereoisomers (IX) preferentially. The loss of the ethylsulphenic acid from the disulphoxide diastereoisomers (II) could be rationalised in terms of the preferred rotamers of the C-17 substituents.

Administration, Topical↗
PubMed1996

Identification of patients with acute AIDS-associated cryptococcal meningitis who can be effectively treated with fluconazole: the role of antifungal susceptibility testing.

No method currently exists to predict which patients with acute AIDS-associated cryptococcal meningitis can be effectively treated with fluconazole. The objective of this study was to determine the relationship of cryptococcal susceptibility to fluconazole, along with clinical variables, to the risk of treatment failure for patients with acute AIDS-associated cryptococcal meningitis. Results of in vitro fluconazole susceptibility testing of cryptococcal isolates and data from two clinical trials were analyzed. Susceptibility to fluconazole was determined by means of both microtiter and macrobroth (M27-P) dilution methods. Treatment was defined as successful if the patient was alive at 10 weeks and if a cerebrospinal fluid culture was sterile at that time. Seventy-six patients receiving fluconazole +/- flucytosine were included; therapy failed for 19. Patients whose therapy failed were more likely to have a positive blood and urine culture and a higher titer in serum and cerebrospinal fluid of cryptococcal antigen, and the MIC of fluconazole against their isolates (as determined by the microtiter method) was more likely to be higher; they were less likely to have received flucytosine. Logistic regression modeling revealed that a negative blood culture, a low MIC of fluconazole (per the microtiter method), and treatment with flucytosine were factors independently associated with successful treatment.

AIDS-Related Opportunistic Infections↗
PubMed1996

Factors associated with prolongation of transport times of emergency pediatric patients requiring transfer to a tertiary care center.

PURPOSE: The purpose of this study was to determine factors associated with longer times to transport of emergency pediatric patients requiring tertiary care. DESIGN: Retrospective case series. SETTING: Emergency pediatric transport service. PARTICIPANTS: Infants and children transported by the transport service at the University of North Carolina Hospitals at Chapel Hill from January 1, 1988, to December 31, 1990. MAIN MEASUREMENTS: The time-to-request, the time from patient arrival at the referring hospital to the time when the request for transfer was received, and the ground time, defined as the time between the transport team's arrival at the referring hospital and their departure, were recorded for each transported patient. RESULTS: Three hundred consecutive children 0 to 16 years (61% male) were transferred. Time-to-request was shorter for trauma patients (median 62 minutes, quartiles 29 and 153 minutes) than for medical patients (median 172 minutes, quartiles 83 and 508 minutes) (P = 0.0001). Infants, children, and adolescents had similar times-to-request of 147 minutes, 129 minutes, and 128 minutes, respectively (P = 0.91). Increased ground times were associated with diagnosis category (median of 40 minutes for medical patients vs 29 minutes for trauma patients) (P = 0.0001), with younger age (median of 46 minutes for infants, 35 minutes for children, and 28 minutes for adolescents) (P = 0.0001), and with the performance of major procedures (median of 35 minutes if no procedures were performed, 38 minutes if one procedure was performed, and 54 minutes if two procedures were performed) (P = 0.039). After the transport team arrived, 13% (40/300) of patients required at least one major procedure prior to transport. CONCLUSIONS: Increased time-to-request for patients with medical diagnoses, increased ground times for younger patients and patients with medical diagnoses, and failure to perform necessary procedures contribute to a prolongation of the time-to-transport of emergency pediatric patients. The magnitude of the impact of these longer transport times on outcome is unknown.

Academic Medical Centers↗