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Biomedical subjects

B A Williams

Publications and source records attributed to B A Williams.

At least 19 recordsLinked to original sources

Strong predictive value of TIMI risk score analysis for in-hospital and long-term survival of patients with right ventricular infarction.

BACKGROUND: While right ventricular myocardial infarction is associated with increased in-hospital morbidity and mortality, prognostic risk factors for in-hospital and long-term mortality are poorly defined. OBJECTIVES: To evaluate the prognostic value of TIMI (Thrombolysis in Myocardial Infarction) risk score analysis in patients with right ventricular myocardial infarction (RVI). DESIGN: Retrospective analysis of a community population. SETTING: Mayo Clinic Coronary Care Unit. PATIENTS: One hundred and two patients with RVI from 580 consecutive patients from Rochester, Minnesota admitted to the Coronary Care Unit with acute inferior or lateral wall myocardial infarction from January 1988 through March 1998. MEASUREMENT: Combined TIMI risk score analysis with in-hospital and long-term mortality. RESULTS: In-hospital morbidity (RVI: 54.9% vs non-RVI: 22.2%; P<0.001) and mortality (RVI: 21.6% vs non-RVI: 6.9%;P <0.001) were increased in patients with RVI. The TIMI risk score predicted risk (per one point increase in TIMI score) for in-hospital mortality (OR 1.23, 95% CI 1.02-1.51, P=0.037) and long-term mortality (OR 1.57, 95% CI 1.25-1.96, P<0.001). Patients with RVI whose TIMI risk score was >or=4 had significantly worse long-term survival compared to those patients with RVI and TIMI score <4 (P=0.006). CONCLUSIONS: In-hospital morbidity and mortality, and long-term mortality are increased by right ventricular infarction and can be accurately predicted by the initial TIMI risk score.

Aged↗

Bundle branch block as a predictor of long-term survival after acute myocardial infarction.

Using a community-based population of patients with acute myocardial infarction (AMI), we sought to: (1) determine the prevalence of bundle branch block (BBB) on the presenting electrocardiogram (ECG), (2) compare the clinical characteristics and the treatment administered to patients with and without BBB, and (3) determine the association of BBB with mortality. We analyzed the admission ECGs of 894 consecutive patients with AMI from Olmsted County, Minnesota, seen at our institution from January 1988 to March 1998. Of these, 53 had left BBB (LBBB) (5.9%) and 60 had right BBB (RBBB) (6.7%). Patients with BBB were more likely to be older, have a history of AMI or hypertension, and to be in Killip class >I at presentation. They were less likely to receive primary reperfusion therapy, beta blockers, or heparin, but more likely to receive angiotensin-converting enzyme inhibitors. They had lower mean predischarge ejection fractions (38 +/- 16% vs 50 +/- 15%, p <0.0001). In-hospital mortality was 13.3%, 17.0%, and 9.1% for patients with RBBB, LBBB, and no BBB, respectively (p = 0.11). Respective postdischarge survival at 1, 3, and 5 years was 80%, 60%, and 50% in the RBBB group, 78%, 56%, and 51% in the LBBB group, and 92%, 85%, and 76% in the group without BBB (p <0.0001). Although BBB was not an independent predictor of mortality on multivariate analysis, the presence of transient or persistent BBB with AMI is an easily recognized clinical marker of increased mortality. Our conclusion from this study is that in a community-based population, patients who had LBBB or RBBB at the time of AMI had lower predischarge ejection fractions and higher in-hospital and long-term unadjusted mortality.

Aged↗

Characteristics of presenting electrocardiograms of acute myocardial infarction from a community-based population predict short- and long-term mortality.

To investigate the relevance of presenting electrocardiographic (ECG) patterns to short- and long-term mortality in nonreferral patients with acute myocardial infarction (AMI), 6 ECG patterns were analyzed. A consecutive series of 907 patients from Olmsted County, Minnesota, admitted to the Mayo Clinic Cardiac Care Unit from January 1, 1988 to March 31, 1998 for acute myocardial infarction comprised the study population. ECG patterns and distribution in the population were: (1) ST elevation alone (20.8%), (2) ST elevation with ST depression (35.2%), (3) normal or nondiagnostic electrocardiograms (18.5%), (4) ST depression alone (11.8%), (5) T-wave inversion only (10.7%), and (6) new left bundle branch block (LBBB) (3.0%). Seven- and 28-day mortalities varied significantly (p <0.01) among the 6 ECG groups. Respective mortalities were 3.0% and 6.0% for patients with normal or nondiagnostic electrocardiograms, 3.1% and 5.2% for T-wave inversion only, 7.4% and 10.6% for ST elevation alone, 9.4% and 13.1% for ST depression alone, 10.3% and 13.8% for ST elevation with ST depression, and 18.5% and 22.2% for new LBBB. Length of hospital stay (LOS) also varied among the ECG pattern groups (p <0.001) with the longest average LOS being in the new LBBB group (12.5 days). Long-term survival was similar among 5 ECG pattern groups (45% to 55% at 8 years from discharge) with the exception of LBBB (20% at 8 years). Among non-LBBB groups, ST-segment depression with or without ST elevation was associated with increased short-term mortality. Also, in this community-based population, 18.5% of patients had normal or nondiagnostic electrocardiograms.

Adult↗

Effect of concomitant or very early statin administration on in-hospital mortality and reinfarction in patients with acute myocardial infarction.

In a retrospective analysis, 66 patients identified as having received a statin drug within 24 hours of admission for acute myocardial infarction were matched 3:1 with a control group of 198 patients not treated with a statin agent. End points of in-hospital mortality and in-hospital reinfarction were significantly lower in the statin-treated group, pointing to a benefit from very early statin treatment in acute myocardial infarction.

Aged↗

Differences in normal values for murine white blood cell counts and other hematological parameters based on sampling site.

OBJECTIVE AND DESIGN: The effect of blood sampling site on the hemogram and neutrophil adhesion molecules was examined in BALB/c mice. MATERIALS AND METHODS: Blood samples were drawn from the tail, eye, and heart during anesthesia with ketamine and xylazine. Cell numbers were quantified with an automated counter and flow cytometry was used to quantify CD11b and CD18. RESULTS: Total white blood cell (WBC) counts were highest from tail, lower from eye, and significantly lower from heart blood. In general, differences between tail and heart counts reflected changes in all cell types. RBCs, platelets and hematocrits were significantly increased in tail compared to heart blood. Although CD18 levels were not different, CD11b was significantly higher on neutrophils from tail compared to heart blood. CONCLUSIONS: In anesthetized BALB/c mice, sampling site readily influences blood counts and neutrophil CD11b. The findings underscore the need to standardize sampling site when measuring these parameters.

Anesthesia↗

Effects of signaled versus unsignaled delay of reinforcement on choice.

Pigeons chose between 5-s and 15-s delay-of-reinforcement alternatives. The first key peck to satisfy the choice schedule began a delay timer, and food was delivered at the end of the interval. Key pecks during the delay interval were measured, but had no scheduled effect. In Experiment 1, signal conditions and choice schedules were varied across conditions. During unsignaled conditions, no stimulus change signaled the beginning of a delay interval. During differential and nondifferential signal conditions, offset of the choice stimuli and onset of a delay stimulus signaled the beginning of a delay interval. During differential signal conditions, different stimuli were correlated with the 5-s and 15-s delays, whereas the same stimulus appeared during both delay durations during nondifferential signal conditions. Pigeons showed similar, extreme levels of preference for the 5-s delay alternative during unsignaled and differentially signaled conditions. Preference levels were reliably lower with nondifferential signals. Experiment 2 assessed preference with two pairs of unsignaled delays in which the ratio of delays was held constant but the absolute duration was increased fourfold. No effect of absolute duration was found. The results highlight the importance of delayed primary reinforcement effects and challenge models of choice that focus solely on conditioned reinforcement.

Animals↗

Two-factor theory has strong empirical evidence of validity.

Traditional two-factor theory is supported by parallels in the clinical literature. Theoretical problems with two-factor theory are obviated by the role of safety signals, which serve as positive conditioned reinforcers and retard the extinction of conditioned fear.

Animals↗

Intercessory prayer and cardiovascular disease progression in a coronary care unit population: a randomized controlled trial.

OBJECTIVE: To determine the effect of intercessory prayer, a widely practiced complementary therapy, on cardiovascular disease progression after hospital discharge. PATIENTS AND METHODS: In this randomized controlled trial conducted between 1997 and 1999, a total of 799 coronary care unit patients were randomized at hospital discharge to the intercessory prayer group or to the control group. Intercessory prayer, ie, prayer by 1 or more persons on behalf of another, was administered at least once a week for 26 weeks by 5 intercessors per patient. The primary end point after 26 weeks was any of the following: death, cardiac arrest, rehospitalization for cardiovascular disease, coronary revascularization, or an emergency department visit for cardiovascular disease. Patients were divided into a high-risk group based on the presence of any of 5 risk factors (age = or >70 years, diabetes mellitus, prior myocardial infarction, cerebrovascular disease, or peripheral vascular disease) or a low-risk group (absence of risk factors) for subsequent primary events. RESULTS: At 26 weeks, a primary end point had occurred in 25.6% of the intercessory prayer group and 29.3% of the control group (odds ratio [OR], 0.83 [95% confidence interval (CI), 0.60-1.14]; P=.25). Among high-risk patients, 31.0% in the prayer group vs 33.3% in the control group (OR, 0.90 [95% CI, 0.60-1.34]; P=.60) experienced a primary end point. Among low-risk patients, a primary end point occurred in 17.0% in the prayer group vs 24.1% in the control group (OR, 0.65 [95% CI, 0.20-1.36]; P=.12). CONCLUSIONS: As delivered in this study, intercessory prayer had no significant effect on medical outcomes after hospitalization in a coronary care unit.

Age Factors↗

An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells.

The biophysical and pharmacological properties of an oxygen-sensitive background K+ current in rat carotid body type-I cells were investigated and compared with those of recently cloned two pore domain K+ channels. Under symmetrical K+ conditions the oxygen-sensitive whole cell K+ current had a linear dependence on voltage indicating a lack of intrinsic voltage sensitivity. Single channel recordings identified a K+ channel, open at resting membrane potentials, that was inhibited by hypoxia. This channel had a single channel conductance of 14 pS, flickery kinetics and showed little voltage sensitivity except at extreme positive potentials. Oxygen-sensitive current was inhibited by 10 mM barium (57% inhibition), 200 microM zinc (53% inhibition), 200 microM bupivacaine (55% inhibition) and 1 mM quinidine (105 % inhibition). The general anaesthetic halothane (1.5%) increased the oxygen-sensitive K+ current (by 176%). Halothane (3 mM) also stimulated single channel activity in inside-out patches (by 240%). Chloroform had no effect on background K+ channel activity. Acidosis (pH 6.4) inhibited the oxygen-sensitive background K+ current (by 56%) and depolarised type-I cells. The pharmacological and biophysical properties of the background K+ channel are, therefore, analogous to those of the cloned channel TASK-1. Using in situ hybridisation TASK-1 mRNA was found to be expressed in type-I cells. We conclude that the oxygen- and acid-sensitive background K+ channel of carotid body type-I cells is likely to be an endogenous TASK-1-like channel.

Acidosis↗

Estimating the extent of degradation of ruminant feeds from a description of their gas production profiles observed in vitro: comparison of models.

An evaluation of general models that describe gas production profiles is presented. The models are derived from first principles by considering a simple three-pool scheme and permit the extent of ruminal degradation to be calculated, as described in the companion paper. The models evaluated were the generalized Mitscherlich, simple Mitscherlich, generalized Michaelis-Menten, simple Michaelis-Menten, Gompertz, and logistic. Five sets of gas production data consisting of 216 curves, obtained using a wide range of feeds (including straw, hay, silage, grain and various byproducts), were analysed to study the performance of these gas production models. Application of the non-sigmoidal models (simple Mitscherlich and Michaelis-Menten) to the data resulted in convergence problems and these models were found to be inadequate in many cases. Based on results of a pairwise comparison between models (variance ratio test), ranking of residual mean squares, lack-of-fit test, and of analyses of residuals, the generalized Mitscherlich and the generalized Michaelis-Menten models seemed particularly suited because of their flexibility to encompass sigmoidal and non-sigmoidal shapes of gas production profiles, whether symmetrical or not.

Animal Feed↗

Process analysis in outpatient knee surgery: effects of regional and general anesthesia on anesthesia-controlled time.

BACKGROUND: The performance of anesthetic procedures before operating room entry (e.g., with either general or regional anesthesia [RA] induction rooms) should decrease anesthesia-controlled time in the operating room. The authors retrospectively studied the associations between anesthesia techniques and anesthesia-controlled time, evaluating one surgeon performing a single procedure over a 3-yr period. The authors hypothesized that, using the anesthesia care team model, RA would be associated with reduced anesthesia-controlled time compared with general anesthesia (GA) alone or combined general-regional anesthesia (GA-RA). METHODS: The authors queried an institutional database for 369 consecutive patients undergoing the same procedure (anterior cruciate ligament reconstruction) performed by one surgeon over a 3-yr period (July 1995 through June 1998). Throughout the period of study, anesthesia staffing consisted of an attending anesthesiologist medically directing two nurse anesthetists in two operating rooms. Anesthesia-controlled time values were compared based on anesthesia techniques (GA, RA, or GA-RA) using one-way analysis of variance, general linear modeling using time-series and seasonal adjustments, and chi-square tests when appropriate. P < 0. 05 was considered significant. RESULTS: RA was associated with the lowest anesthesia-controlled time (11.4 +/- 1.3 min, mean +/- 2 SEM). GA-RA (15.7 +/- 1.0 min) was associated with lower anesthesia-controlled time than GA used alone (20.3 +/- 1.2 min). CONCLUSIONS: When compared with GA without an induction room for outpatients undergoing anterior cruciate ligament reconstruction, RA with an induction room was associated with the lowest anesthesia- controlled time. Managers must weigh the costs and time required for anesthesiologists and additional personnel to place nerve blocks or induce GA preoperatively in such a staffing model.

Adult↗

Fate restriction in limb muscle precursor cells precedes high-level expression of MyoD family member genes.

The mechanisms by which pluripotent embryonic cells generate unipotent tissue progenitor cells during development are unknown. Molecular/genetic experiments in cultured cells have led to the hypothesis that the product of a single member of the MyoD gene family (MDF) is necessary and sufficient to establish the positive aspects of the determined state of myogenic precursor cells: i.e., the ability to initiate and maintain the differentiated state (Weintraub, H., Davis, R., Tapscott, S., Thayer, M., Krause, M., Benezra, R., Blackwell, T. K., Turner, D., Rupp, R., Hollenberg, S. et al. (1991) Science 251, 761-766). Embryonic cell type determination also involves negative regulation, such as the restriction of developmental potential for alternative cell types, that is not directly addressed by the MDF model. In the experiments reported here, phenotypic restriction in myogenic precursor cells is assayed by an in vivo 'notochord challenge' to evaluate their potential to 'choose' between two alternative cell fate endpoints: cartilage and muscle (Williams, B. A. and Ordahl, C. P. (1997) Development 124, 4983-4997). Two separate myogenic precursor cell populations were found to be phenotypically restricted while expressing the Pax3 gene and prior to MDF gene activation. Therefore, while MDF family members act positively during myogenic differentiation, phenotypic restriction, the negative aspect of cell specification, requires cellular and molecular events and interactions that precede MDF expression in myogenic precursor cells. The qualities of muscle formed by the determined myogenic precursor cells in these experiments further indicate that their developmental potential is intermediate between that of myoblastic stem cells taken from fetal or adult tissue (which lack mitotic and morphogenetic potential when tested in vivo) and embryonic stem cells (which are multipotent). We hypothesize that such embryonic myogenic progenitor cells represent a distinct class of determined embryonic cell, one that is responsible for both tissue growth and tissue morphogenesis.

Animals↗

S.T.E.P.S.: a comprehensive program for controlling and monitoring access to thalidomide.

In July 1998, the US Food and Drug Administration approved the marketing of thalidomide for the treatment of cutaneous manifestations of erythema nodosum leprosum. To ensure that fetal exposure to this teratogenic agent does not occur, the manufacturer has instituted a comprehensive program to control prescribing, dispensing, and use of the drug. This program, known as the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S. [Celgene Corporation, Warren, New Jersey]), is based in part on experience gained with other drugs--specifically isotretinoin and clozapine--that offer important clinical benefits but carry the potential for serious harm. To achieve its goal of the lowest possible incidence of drug-associated teratogenicity, the S.T.E.P.S. program uses a three-pronged approach: (1) controlling access to the drug; (2) educating prescribers, pharmacists, and patients; and (3) monitoring compliance. Clinicians who wish to prescribe thalidomide must be registered in the S.T.E.P.S. Prescriber Registry and agree to prescribe the drug in accordance with S.T.E.P.S. patient eligibility criteria and monitoring procedures. Pharmacies must also register and agree to comply with patient identification and monitoring criteria. Finally, patients receive visual aids, including a videotape, written material, and verbal counseling about the benefits and risks of thalidomide therapy, the importance of not becoming pregnant during therapy, and the types of contraception required (including emergency contraception) and their availability. Women of childbearing potential must agree to undergo pregnancy testing before starting therapy and on a regular schedule during therapy. All patients must agree to complete a confidential survey about their compliance with contraception, testing, and drug therapy. The manufacturer is monitoring survey results and outcome data and is prepared to make whatever modifications to the S.T.E.P.S. program are necessary to ensure its effectiveness. In addition to minimizing the potential risk for fetal harm associated with thalidomide therapy, the S.T.E.P.S. program may provide a model for future cases in which a drug offers compelling benefits but poses profound risks unless its distribution is carefully controlled.

Dermatologic Agents↗

Kinetics of rate-dependent shortening of action potential duration in guinea-pig ventricle; effects of IK1 and IKr blockade.

1. The kinetics of shortening of action potential duration (APD) following an increase in pacing rate, from 2 to 3.3 Hz, was characterized in guinea-pig ventricular preparations. Terikalant (RP62719), an inhibitor of the inwardly rectifying K+ current (IK1), and dofetilide, a specific inhibitor of the rapidly activating delayed-rectifier current (IKr), were applied to determine the effect of inhibition of these ion currents on slow APD shortening. 2. Action potentials were recorded from isolated guinea-pig ventricular myocytes using the perforated-patch patch-clamp technique, and monophasic action potentials were recorded from Langendorff-perfused guinea-pig ventricles using a contact epicardial probe. 3. Under control conditions, after an increase in pacing rate, APD immediately decreased, and then shortened slowly with an exponential time course. In ventricular myocytes, the time constant of this exponential shortening was 28+/-4 s and the amount of slow shortening was 21.9+/-0.9 ms (n=8) for an increase in rate from 2 to 3.3 Hz. Similar values were observed in Langendorff-perfused ventricles. 4. Terikalant dose-dependently increased APD and the increase was enhanced by rapid pacing ('positive' rate-dependence). The drug dose-dependently decreased the time constant of shortening and amount of slow APD shortening. In contrast, dofetilide, an inhibitor of IKr, which shows 'reverse' rate-dependent APD widening, had no significant effect on the time constant or amount of slow shortening. 5. These observations suggest that IK1 plays a role in rate-dependent shortening of APD. The results appear to support the hypothesis that 'reverse' rate-dependent effects of IKr blockers are due to these drugs not affecting the ion current(s) mediating intrinsic rate-dependent slow shortening of APD.

Action Potentials↗

Value transmission in discrimination learning involving stimulus chains.

Rats learned a series of reversals of a positional discrimination in which responses to one lever led to delayed food and responses to a second lever led to no food. Interpolated within the delays leading to the different outcomes were two-link stimulus chains. The pairing of each stimulus element with the delayed outcome of food or no food varied across reversals. Either stimulus element could have the same correlation with outcome as occurred on the preceding reversal or the opposite correlation as on the preceding reversal. New reversals were acquired more quickly when both stimulus elements had the same status as during the preceding reversal, and were acquired most slowly when both stimulus elements had the opposite status as that of the preceding reversal. The rate of learning was intermediate when only one of the stimulus elements had the same status as that during the preceding reversal. All of the data are compatible with an interpretation in terms of backward chaining of stimulus value.

Animals↗

Associative competition in operant conditioning: blocking the response-reinforcer association.

Naive rats were trained to leverpress with a 30-sec delay-of-reinforcement contingency from the start of training. In Experiment 1, the delay interval for different groups of subjects included a signal in the first 5 sec, a signal in the last 5 sec, or no signal at any time. Rats with the signal at the start of the delay interval learned most rapidly. Rats with the signal at the end of the delay failed to learn. In Experiment 2, a choice procedure was used, in which each of two levers was associated with its own 30-sec delay of reinforcement. The delay for one lever included a 5-sec signal at the end of the delay. The delay for the second lever had no signal in its 30-sec delay. Preference was in favor of the lever without the signal in the delay interval. The results demonstrate that the acquisition of new response can be blocked in a manner analogous to the blocking of Pavlovian conditioning.

Animals↗