Biomedical subjects
Publications and source records attributed to T J Lewis.
A palm computer with a 160 x 160-pixel display and 16-bit color depth can display useable images if the viewing software supports a larger image file size and zooming functions. Flash memory modules are now available. Storage of large image files is no longer a problem.
BACKGROUND: The cost associated with education of residents is of interest from an educational as well as a political perspective. Most studies report a single institution's actual incurred costs, based on traditional cost accounting methods. We quantified the minimum instructional and program-specific administrative costs for residency training in internal medicine. METHODS: Using the Accreditation Council for Graduate Medical Education program requirements for internal medicine as minimum standards for teaching and administrative effort, we quantified the minimum instructional and administrative costs for sponsorship of an accredited residency program in internal medicine. We also analyzed the impact of resident complement and program curricular emphasis (outpatient, inpatient, or traditional) on the per-resident cost. The main outcome measure was the minimum annual per-resident cost of instruction and program-specific administration. RESULTS: Using the assumptions in this model, we estimated the annual cost per resident of implementing the program requirements to be $50,648, $35,477, $28,517, and $26,197 for inpatient intensive residency programs with resident complements of 21, 42, 84, and 126, respectively. For outpatient intensive residency programs of identical resident complements, we estimated the annual per-resident cost to be $58,025, $42,853, $35,894, and $33,574 for similar resident complements. Fixed costs mandated by the program requirements, which did not vary across program size or configuration, were estimated to be $640,737. CONCLUSIONS: There are fixed and variable costs associated with sponsorship of accredited internal medicine residency programs. The minimum cost per resident of education and departmental administration varies inversely with program size within the sizes examined.
Recent evidence suggests that electrical coupling plays a role in generating oscillatory behaviour in networks of neurons; however, the underlying mechanisms have not been identified. Using a cellular automata model proposed by Traub et al (Traub R D, Schmitz D, Jefferys J G and Draguhn A 1999 High-frequency population oscillations are predicted to occur in hippocampal pyramidal neural networks interconnected by axo-axonal gap junctions Neuroscience 92 407-26), we describe a novel mechanism for self-organized oscillations in networks that have strong, sparse random electrical coupling via gap junctions. The network activity is generated by random spontaneous activity that is moulded into regular population oscillations by the propagation of activity through the network. We explain how this activity gives rise to particular dependences of mean oscillation frequency on network connectivity parameters and on the rate of spontaneous activity, and we derive analytical expressions to approximate the mean frequency and variance of the oscillations. In doing so, we provide insight into possible mechanisms for frequency control and modulation in networks of neurons.
We demonstrate that a biphasic shock is more effective than a monophasic shock at eliminating reentrant electrical activity in an ionic model of cardiac ventricular electrical activity. This effectiveness results from early hyperpolarization that enhances the recovery of sodium inactivation, thereby enabling earlier activation of recovering cells. The effect can be seen easily in a model of a single cell and also in a cable model with a ring of excitable cells. Finally, we demonstrate the phenomenon in a two-dimensional model of cardiac tissue.
In the preceding paper, we showed that DNA topoisomerase II from Saccharomyces cerevisiae binds two ATP and rapidly hydrolyzes at least one of them before encountering a slow step in the reaction mechanism. These data are potentially consistent with two different types of reaction pathways: (1) sequential ATP hydrolysis or (2) simultaneous hydrolysis of both ATP. Here, we present results that are consistent only with topoisomerase II hydrolyzing its two bound ATP sequentially. Additionally, these results indicate that the products of the first hydrolysis are released from the enzyme before the second ATP is hydrolyzed. Release of products from both the first and second hydrolyses contributes to the rate-determining process. The proposed mechanism for ATP hydrolysis by topoisomerase II is complex, having nine rate constants. To calculate values for each of these rate constants, a technique of kinetic parameter estimation was developed. This technique involved using singular perturbation theory in order to estimate rate constants, and consequently identify kinetic steps following the rate-determining step.
UNLABELLED: Intrathecal sufentanil provides approximately 2 h of excellent labor analgesia with minimal motor blockade. Epidural sufentanil has received less scrutiny but may provide the same benefits as intrathecal sufentanil. In this study, we compared epidural sufentanil 40 microg after a lidocaine with an epinephrine test dose with intrathecal (i.t.) sufentanil 10 microg with respect to onset and duration of analgesia, degree of motor block, side effect profile, and mode of delivery. Seventy ASA physical status I or II parturients in early labor (< or = 4 cm cervical dilation) were randomized to receive either i.t. sufentanil 10 microg with a combined spinal-epidural technique (CSE) or epidural sufentanil 40 microg (e.p.) after epidural catheter placement and testing with 3 mL of 1.5% lidocaine with epinephrine (15 microg). After the administration of analgesia, pain scores and side effects were recorded for each patient at 5, 10, 15, 20, and 30 min, and every 30 min thereafter, by an observer blinded to the technique used. The study period was completed when the patients requested additional analgesia. All patients, except one, achieved adequate analgesia with the initial study dose and satisfactorily completed the study. There were no demographic differences between the two groups. Pain relief was rapid for all patients; pain scores were significantly lower at 5 and 10 min in the i.t. group versus the e.p. group. The mean duration of analgesia was similar between the e.p. group (127 +/- 40 min) and the i.t. group (110 +/- 48 min). No patient experienced any motor block. Side effects were similar between the two groups, except for pruritus-both the incidence and severity were significantly more profound at 5, 10, 15, 20, and 30 min in the i.t. group. There was no difference in time from analgesic to delivery, incidence of operative or assisted delivery, or cervical dilation at the time of redose. For early laboring patients, epidural sufentanil 40 microg after a lidocaine test dose provides analgesia comparable to that of i.t. sufentanil 10 microg with less pruritus. IMPLICATIONS: We compared the efficacy and side effects of intrathecal sufentanil with epidural sufentanil with a local anesthetic test dose for analgesia during labor. Analgesia was equally good, although the intrathecal group experienced more itching.
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Extracts of tissue showed that prostatic carcinomas contain less leucine aminopeptidase activity than benign prostatic hyperplasia. This is true when activity is expressed as specific activity (P = 0.0033), specific activity/% epithelium (P = 0.0007), activity/wet weight of tissue (P = 0.0028), or activity/wet weight of tissue/% epithelium (P = 0.0005). Almost all histochemically demonstrable activity is located in the epithelium. Enzymatic activities in extracts and in histochemical preparations showed similar differences between carcinoma and benign prostatic hyperplasia and were related (R = -0.38, P = 0.0400) to Gleason's grades. The transurethrally resected prostate cancers studied contained no well-differentiated tumors and a high proportion of poorly differentiated tumors. Histochemical activity is absent in most prostatic carcinomas and decreased in others. This observation is particularly interesting in view of the growing knowledge of tumor suppressor genes.
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Using cylindrical quartz crystal torsional resonators operating at 39 and 75 kHz to generate shear waves in aqueous solutions of the proteins bovine serum albumin and hemoglobin and the polypeptide poly l-glutamic acid, it has been possible to determine the complex dynamic shear viscosities of the solutions. The effects of concentration, pH, and denaturation using various agents have been studied. It is possible to relate the viscosity and configurational elasticity of the solutions, to the intramolecular and intermolecular forces associated with the of the proteins at frequencies between 60 and 400 kHz and attributed to conformational changes of bovine serum albumin and the quaternary doublet interactions of hemoglobin have been confirmed and emphasized by the use of shear waves.
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We simulate the effect of periodic stimulation on a strand of ventricular muscle by numerically integrating the one-dimensional cable equation using the Beeler-Reuter model to represent the transmembrane currents. As stimulation frequency is increased, the rhythms of synchronization [1:1----2:2----2:1----4:2---- irregular----3:1----6:2----irregular----4:1----8:2----...----1:0] are successively encountered. We show that this sequence of rhythms can be accounted for by considering the response of the strand to premature stimulation. This involves deriving a one-dimensional finite-difference equation or "map" from the response to premature stimulation, and then iterating this map to predict the response to periodic stimulation. There is good quantitative agreement between the results of iteration of the map and the results of the numerical integration of the cable equation. Calculation of the Lyapunov exponent of the map yields a positive value, indicating sensitive dependence on initial conditions ("chaos"), at stimulation frequencies where irregular rhythms are seen in the corresponding numerical cable simulations. The chaotic dynamics occurs via a previously undescribed route, following two period-doubling bifurcations. Bistability (the presence of two different synchronization rhythms at a fixed stimulation frequency) is present both in the simulations and the map. Thus, we have been able to directly reduce consideration of the dynamics of a partial differential equation (which is of infinite dimension) to that of a one-dimensional map, incidentally demonstrating that concepts from the field of non-linear dynamics--such as period-doubling bifurcations, bistability, and chaotic dynamics--can account for the phenomena seen in numerical simulations of the cable equation. Finally, we sketch out how the one-dimensional description can be extended, and point out some implications of our work for the generation of malignant ventricular arrhythmias.
Previously, we reported that the activities of several enzymes extracted from prostatic cancers were closely related to the histologic grades (Gleason's grades) of the cancers. The survival of patients was more closely correlated with certain enzymatic activities than with Gleason's grades. Unfortunately, because our assays required relatively large amounts of tissue, the increasing proportion of patients who have needle biopsies as their only surgical procedure had to be excluded from our previous study. We now report a method that permits multiple enzyme assays to be carried out with much smaller amounts of tissue. This method will enable us to avoid the selection inherent in the exclusion of patients who have only needle biopsies and should permit the prospective study of most patients with prostatic carcinoma.
In light of previous reports of alterations in 5'-nucleotidase activity in neoplastic conditions, 5'-nucleotidase activity was examined histochemically in tissue sections and quantified biochemically in extracts of human hyperplastic prostates and prostatic carcinomas obtained surgically. The 5'-nucleotidase activities per mg protein in extracts of 29 prostatic carcinomas were lower (P less than 0.0005) than in extracts from 10 samples of benign prostatic hyperplasia. The 5'-nucleotidase activity per mg protein in extracts of prostatic carcinoma from the 29 patients correlated (R = -0.369, P = 0.049) with the degree of histological differentiation; the extracts of poorly differentiated carcinomas contained low levels of 5'-nucleotidase. When age and histological differentiation (Gleason's grade) were adjusted, the enzyme activity per mg protein correlated (R = 0.242, P = 0.004) with patient survival. When all three parameters were considered together, i.e., histological grade of the tumor, 5'-nucleotidase extracted from the tumor, and age of the patient, they were found to be mutually complementary for the prediction of patient survival (R = 0.388, P = 0.0001). To our knowledge, this is the first report that prostatic epithelium expresses 5'-nucleotidase; further work will be required to define the reasons for the high levels of activity observed in prostates without cancer and for the decrease in the activity in prostatic carcinoma.
The role of solvation and structural equilibria in determining the ultrasonic absorption of aqueous solutions of bovine serum albumin has been investigated using chemical agents to denature the protein in solution. The agents used were methanol, ammonium sulphate, and guanidine hydrochloride. Two different techniques of measurement were used to cover the frequency range 200 kHz to 30 MHz. The results show that only guanidine hydrochloride produces a significant change in ultrasonic absorption even though the other agents were used at concentrations close to those which would produce protein precipitation. The conclusion is that in the above frequency range structural and solvation-related equilibria are unimportant and only perturbation of proton-transfer equilibria associated with the protein amino acid residues leads to the bulk of the ultrasonic absorption.