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Biomedical subjects

P Light

Publications and source records attributed to P Light.

At least 19 recordsLinked to original sources
PubMed2001

A computerized method for identifying incidents associated with adverse drug events in outpatients.

INTRODUCTION: In inpatients, computer monitors have been used to improve the detection of adverse drug events (ADEs). However, similar programs have not been available in outpatients. OBJECTIVE: To describe an approach for detecting incidents suggesting that an ADE may have occurred in outpatients by adapting methods from inpatient computer monitoring and developing terminology searches of electronic medical records. METHODS: One year of information from the outpatient electronic medical record (EMR) at one hospital and its clinics was reviewed. Altogether, 23064 patients and 88514 visits were identified. Patient demographics, medical problem lists, ICD-9 claims, patient allergies, medication history and all clinic visit notes were extracted and merged. We then searched for incidents suggesting that an ADE might be present using four methods: ICD-9 claims, new allergies, computer rules linking laboratory data to known medication exposures, and a medical terminology lexicon (M2D2). In this report, we describe how these search methods were developed to allow for ADE identification. CONCLUSION: The ability to carry out such quality-related work is an example of the benefits of the outpatient EMR that may not be apparent to those institutions considering adopting it.

Adverse Drug Reaction Reporting Systems↗
PubMed2001

Vancomycin-resistant enterococci colonization in patients at seven hemodialysis centers.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are increasing in prevalence at many institutions, and are often reported in dialysis patients. We studied the prevalence of and risk factors for VRE at seven outpatient hemodialysis centers (three in Baltimore, MD, USA, and four in Richmond, VA, USA). METHODS: Rectal or stool cultures were performed on consenting hemodialysis patients during December 1997 to April 1998. Consenting patients were recultured during May to July 1998 (median 120 days later). Clinical and laboratory data and functional status (1 to 10 scale: 1, normal function; 9, home attendant, not totally disabled; 10, disabled, living at home) were recorded. RESULTS: Of 478 cultures performed, 20 (4.2%) were positive for VRE. Among the seven centers, the prevalence of VRE-positive cultures varied from 1.0 to 7.9%. Independently significant risk factors for a VRE-positive culture were a functional score of 9 to 10 (odds ratio 6.9, P < 0.001), antimicrobial receipt within 90 days before culture (odds ratio 6.1, P < 0.001), and a history of injection drug use (odds ratio 5.4, P = 0.004). CONCLUSIONS: VRE-colonized patients were present at all seven participating centers, suggesting that careful infection-control precautions should be used at all centers to limit transmission. In agreement with previous studies, VRE colonization was more frequent in patients who had received antimicrobial agents recently, underscoring the importance of judicious antimicrobial use in limiting selection for this potential pathogen.

Cross Infection↗
PubMed2001

Use of erythropoietin before the initiation of dialysis and its impact on mortality.

Erythropoietin (EPO) is recommended in individuals progressing toward end-stage renal disease (ESRD) to correct anemia and its complications, which are common in this disease. This study evaluated the impact of EPO administered before dialysis on mortality in incident ESRD patients. A total of 4,866 patients whose exposure to pre-ESRD EPO was determined from Health Care Financing Administration 2728 forms were analyzed. The median follow-up was 26.2 months, with 1,107 (22.7%) patients given EPO and 1,892 (38.9%) deaths. EPO use was more common in patients who had insurance before dialysis, remained employed, were started on renal replacement therapy outside the hospital, or initiated on peritoneal dialysis, which could be indicative of early intervention or quality care. The risk of death after starting dialysis was lower for patients treated with EPO before dialysis compared with patients who were not treated (adjusted relative risk 0.80, 95% confidence interval 0.70 to 0.91). There was no direct relationship between predialysis hematocrit and mortality; however, the most significant survival benefit with EPO use was in patients with the highest hematocrit values (adjusted relative risk 0.67, 95% confidence interval, 0.51 to 0.89). The most significant effect of pre-ESRD EPO use was observed during the first 19 months after starting dialysis (adjusted relative risk, 0.81; 95% confidence interval, 0.71 to 0.91), but this benefit diminished in patients with longer follow-up on renal replacement therapy. Use of EPO before dialysis confers a survival benefit to ESRD patients, especially in patients with an adequate hematocrit response before initiation of dialysis.

Aged↗
PubMed2001

A prospective study of vascular access infections at seven outpatient hemodialysis centers.

Vascular access infections are a major cause of morbidity and mortality in hemodialysis patients, and the use of antimicrobials to treat such infections contributes to the emergence and spread of antimicrobial-resistant bacteria. To determine the incidence of and risk factors for vascular access infections, we studied hemodialysis patients at 7 outpatient dialysis centers (4 in Richmond, VA, and 3 in Baltimore, MD) during December 1997 to July 1998. Vascular access infections were defined as local signs (pus or redness) at the vascular access site or a positive blood culture with no known source other than the vascular access; and hospitalization or receipt of an intravenous (IV) antimicrobial. A total of 796 patients were followed for 4,134 patient-months. The vascular access infection rate was 3.5/100 patient-months, ie, patients had a 3.5% risk of infection each month. Independent risk factors were the specific dialysis unit where the patient was treated (relative hazard varying from 1.0 to 4.1 among the 7 centers), catheter access (relative hazard, 2.1 v implanted access), albumin level (relative hazard, 2.4 for lowest v highest quartile), urea reduction ratio (relative hazard, 2.2 for lowest v highest quartile), and hospitalizations during the previous 90 days (relative hazard, 4.9 for >/=6 v zero hospitalizations). These data confirm that vascular access infections are common in hemodialysis patients and that infection rates differ substantially among different centers. Catheter use should be minimized to reduce these infections. Additionally, the possibility that improved serum albumin and urea reduction ratio could reduce vascular access infections should be evaluated.

Aged↗
PubMed2000

Azimilide (Procter & Gamble).

Azimilide is a class III anti-arrhythmic agent under development by Procter & Gamble. In December 1998, the company submitted an NDA with the FDA seeking an indication for the maintenance of sinus heart rhythm in patients with various forms of supraventricular arrhythmia. By November 1997, the drug was being evaluated in clinical trials for its use in patients with implantable cardioverter defibrillators (ICDs). The study was to examine its ability to reduce the frequency and severity of ICD electrical discharges. As of August 1999, azimilide was in phase I development by Tanabe Seiyaku in Japan, for the potential treatment of arrhythmia. Results of a pivotal clinical trial, presented at the annual meeting of the Society for Neuroscience in November 1998, demonstrated azimilide to prolong the arrythmia-free period in patients suffering from atrial fibrillation. Phase III clinical trials so far have involved patients with supraventricular and ventricular arrhythmias. Trial results from the ASAP (Azimilide Supraventricular Arrhythmia Program Trial), showed that azimilide significantly prolonged the arrythmia-free period in patients suffering from atrial fibrillation. There were three deaths in the azimilide group compared to one in the placebo group. The safety and efficacy of azimilide in 6000 patients who have suffered a heart attack is currently under study in the phase III ALIVE (azimilide post-infarct survival evaluation) multicenter trial, which commenced in centers in the US and Europe in October 1997.

Journal Article↗
PubMed1999

Hemodialysis adequacy in Network 5: disparity between states and the role of center effects.

The purpose of this study was to determine whether an observed difference in hemodialysis adequacy between states in Network 5 was due to variations in patient characteristics and to what extent dialysis center effects played a role in the observed disparity between states. This was a retrospective observational study of 6,969 patients dialyzed at centers in Maryland and Virginia. There were 3,919 patients on hemodialysis at 89 facilities in Virginia and 3,050 subjects dialyzed at 65 centers in Maryland. The mean urea reduction ratio (URR) was higher in Virginia compared with Maryland (68.2 +/- 0.1% v 66.0 +/- 0.2%, P < 0.0001, respectively), and there continued to be a mean difference in URR of 1.8% between VA and MD (P < 0.0001) after adjusting for several covariates. The differences in URR between states varied depending on facility proprietary status, size as measured by number of stations, and relationship to hospital (free-standing or hospital-based). Furthermore, the center where a patient dialyzed, when treated as a fixed effect, accounted for 15% of the variance in URR. The mean difference of 1.8% in URR between states persisted in a mixed-effects model that included all covariates along with adjusting for dialysis centers as a random effect. The disparity in dialysis adequacy between states in Network 5 could not be accounted for by demographic characteristics, case mix factors, or a large center effect observed in the region. Therefore, we conclude that underlying national reports on dialysis adequacy are heterogeneous results related to differences across regions such as states within a given Network. This difference between states is not explained by the strong center effect found on adequacy in this population of hemodialysis patients.

Blood Urea Nitrogen↗
PubMed1999

Pamicogrel (Kanebo).

Pamicogrel is a cyclooxygenase inhibitor with platelet anti-aggregatory properties which is under development by Kanebo for chronic arterial occlusion. It also has potential in both prophylaxis and treatment of ischemic brain injury. An NDA was submitted in Japan in April 1997. The effects of the drug on platelet aggregation were originally disclosed in EP-00159677, while the later European patent, EP-00560136, claims its use in brain dysfunction induced by hypoxia arising from disturbance of cerebral circulation, such as cerebral hemorrhage or cerebral infarction.

Journal Article↗
PubMed1999

Nesiritide citrate (Scios).

Nesiritide citrate is a human brain natriuretic peptide under development by Scios for the potential treatment of congestive heart failure (CHF). An NDA was submitted to the US FDA in April 1998 for approval to market nesiritide citrate for short-term CHF. Scios is expecting to launch this product by mid-1999. Animal studies at Scios have also indicated that human brain natriuretic peptide may be useful in the management of acute hypertension associated with numerous surgical procedures. Scios has estimated the potential market for this drug to be 250-300 million dollars in the US alone.

Journal Article↗
PubMed1998

Hypothyroidism decreases the ATP sensitivity of KATP channels from rat heart.

The effects of thyroid status on the properties of ATP-sensitive potassium channels were investigated. Single-channel recordings were made using excised inside-out membrane patches from enzymatically dissociated ventricular myocytes from hearts of control and thyroidectomized rats and each group was studied with and without administration of thyroid hormone. In patches excised from hypothyroid myocytes the IC50 for ATP inhibition of KATP channels was 110 micro m. This value was 3-fold higher than the IC50 in control myocytes (43 micro m). Treatment of hypothyroid rats to restore physiological levels of thyroid hormone (tri-iodothyronine, T3), resulted in a return to normal ATP-sensitivity (IC50 = 46 micro M). In patches from animals rendered hyperthyroid, the IC50 for ATP was 50 micro M and this value was not significantly different from the control. There was no difference in the cooperativity of ATP-binding (Hill coefficient, nH) among control (nH = 2.2), hypothyroid (nH = 2.1), T3-treated (nH = 2.0) and hyperthyroid groups (nH = 2.4). The unitary conductance was unchanged and there was no apparent change in intraburst kinetics between examples of single KATP channels from control and hypothyroid rats. Action potentials recorded in myocytes from hypothyroid rats were significantly shortened by 50 micro M levcromakalim, a KATP channel opener (P < 0.001) but unchanged in control myocytes.We conclude that hypothyroidism significantly decreased the ATP-sensitivity of KATP channels, whereas the induction of hyperthyroid conditions did not alter the ATP-sensitivity of these channels. Thus, hypothyroidism is likely to have important physiological consequences under circumstances in which KATP channels are activated, such as during ischemia.

Action Potentials↗
PubMed1997

Spatial cognition in language-impaired children.

Limited research evidence is available concerning the spatial abilities of children with specific language impairments. This paper reports a study of the ability of such children to use plan drawings. The participants were 23 language-impaired (LI) children (12 from special boarding schools, 11 from language units within mainstream primary schools), whose performance was compared with that of 23 non-language-impaired (NLI) children. The children were matched for age, their overall age range being between 7;0-11;11 (mean age 8;6). Tasks involved the production and utilisation of plan drawings of a model house. With one exception, results indicated that the LI children showed no deficit in ability on such tasks, and indeed out-performed their NLI peers on many of them. Implications of these findings are discussed.

Aptitude Tests↗
PubMed1997

Annotation: computers for learning: psychological perspectives.

The research literature on the use of computers in support of learning is already vast. In this review, the focus is on children's learning, and on the way in which psychological theories of learning have informed (and to a lesser extent, been informed by) developments in the field of computer-based learning. Associationist, constructivist, and social-constructivist approaches are explored, and issues of equity, access, and special learning needs are addressed. It is concluded that computers have led to, and will continue to lead to, significant changes in both what and how children learn.

Adolescent↗
PubMed1996

Modulation of muscle contractility during fatigue and recovery by ATP sensitive potassium channel.

The activity of ATP-sensitive potassium channels of skeletal muscle is controlled by changes in the bioenergetic state of the cell. These channels are inactive in unfatigued muscle and become activated during fatigue. It has been postulated that ATP-sensitive potassium channels shorten the action potential duration, increase the potassium efflux and contribute to the decrease in force during fatigue. Although blocking ATP-sensitive potassium channels during fatigue prolongs the action potential duration and decreases the potassium efflux as expected, it does not affect the rate of fatigue development as observed from the decrease in tetanic force. Even though such results are not consistent with the hypothesis that ATP-sensitive potassium channels contribute to the decrease in force during fatigue, a reduced capacity of skeletal muscles to recover their tetanic force following fatigue is also observed when ATP-sensitive potassium channels are blocked during fatigue, suggesting that these channels have a myoprotective effect. It is thus possible that removing this myoprotection during fatigue results in deleterious effects which counteract the expected slower decrease in force. However ATP-sensitive potassium channel openers also fall to affect the rate of fatigue development. Therefore, the results obtained so far do not support the hypothesis that ATP-sensitive potassium channels contribute to the decrease in force during fatigue.

Adenosine Triphosphate↗
PubMed1995

Effect of tolbutamide on the rate of fatigue and recovery in frog sartorius muscle.

The goal of this study was to determine how blocking ATP-sensitive K+ channels with tolbutamide affects the excitability and contractility of intact frog sartorius muscle during fatigue development. Fatigue was elicited with one tetanic contraction every sec for 3 min. During fatigue the resting potential decreased by 10 mV although the action potential overshoot remained constant. The addition of 2 mmol.liter-1 tolbutamide 60 min before fatigue did not modify the effect of fatigue on the resting potential and action potential overshoot. During fatigue development the half-repolarization time of control muscles increased by 0.26 msec in control muscles, although it increased by 0.77 msec in the presence of 2 mmol.liter-1 tolbutamide; the difference was significant. The decrease in force during fatigue development was not affected by 2 mmol.liter-1 tolbutamide (added 60 min before fatigue), whereas the recovery of force after fatigue was slower in tolbutamide- exposed muscles than in control muscles. Addition of 2 mmol.liter-1 tolbutamide after 5 min of recovery reduced the recovery rate of the resting potential and half-repolarization time, but did not affect the recovery of tetanic force during the first 40 min. Our results are consistent with the hypothesis that ATP-sensitive K+ channels are activated during fatigue development and that they contribute to the repolarization phase of action potentials, but they do not support the hypothesis that ATP-sensitive K+ channels contribute to the decrease in force.

Action Potentials↗
PubMed1993

Tolbutamide, but not glyburide, affects the excitability and contractility of unfatigued frog sartorius muscle.

The goal of this study was to characterize the effects of tolbutamide and glyburide, two known KATP channel blockers, on intact, unfatigued sartorius muscle fibres of the frog, Rana pipiens. Tetanic contractions were elicited by field stimulation with 200 ms long train of pulses (0.5 ms, 6 V, 140 Hz). Resting and action potentials were measured using conventional microelectrodes. At pHo 7.2 (extracellular pH), the tetanic force was unaffected by 0.5 mM and 1.0 mM tolbutamide, but at 2.0 mM it decreased by 15.5 +/- 1.0%. The effect of tolbutamide on the tetanic force was significantly greater at pHo 6.4: all three tolbutamide concentrations caused a significant decrease in tetanic force, being 62.3 +/- 9.4% at 2 mM. In the presence of tolbutamide a large number of fibres became unexcitable at pHo 6.4, but not at pHo 7.2. Glyburide at 10 microM, on the other hand, caused a 5-7% decrease in tetanic force at both pHo 6.4 and 7.2, but no further decreases in tetanic force were observed when the glyburide concentration was increased up to 100 microM. Unlike tolbutamide, glyburide did not affect the excitability of muscle fibres, but significantly prolonged the repolarization phase of action potentials, especially at pHo 6.4. We suggest that several of the tolbutamide effects reported in this study cannot be accounted for by a direct effect on KATP channels, and that the large decrease in membrane excitability and muscle contractility in the presence of tolbutamide must seriously be taken into consideration when this channel blocker is used to study the physiological role of KATP channels in intact muscle fibres.

Action Potentials↗
PubMed1992

Hydroxysteroid dehydrogenase activity associated with sexual differentiation in embryos of the turtle Trachemys scripta.

Many turtles exhibit temperature-dependent sex determination. We have examined the hypothesis that incubation temperature causes a differential expression of steroidogenic enzymes in embryonic turtles. The activities of three steroidogenic enzymes were studied histochemically in turtle (Trachemys scripta) embryos at different developmental stages: sexually undifferentiated (Stage 15), differentiating (Stage 17), and differentiated (Stage 26; i.e., hatchling). Steroidogenic enzymes were detected in several tissues prior to, during, and after gonadal differentiation in embryos incubated at both male-producing and female-producing temperatures. In all embryos, ene-5-3 beta-hydroxysteroid dehydrogenase (HSDH) was detected only in adrenal tissue. 3 alpha-HSDH was localized in adrenal tissue, as well as in the mesonephros and liver. 17 beta-HSDH was evident in mesonephric, hepatic, and gut tissues. In hatchlings, ene-5-3 beta-HSDH and 3 alpha-HSDH were evident in the adrenal gland, whereas 3 alpha-HSDH and 17 beta-HSDH were present in the mesonephros and liver. While there was some variation in the activities of these enzymes during development, no temperature-specific pattern was apparent. At no stage were the enzymes observed in genital ridge/gonad. Our results show that T. scripta embryos possess enzymes necessary for steroid hormone synthesis. The segregated distributions of the enzymes suggest that a multi-organ regulatory system may mediate embryonic steroidogenesis. Our results do not indicate the genital ridge/gonad the principle site of steroid synthesis, although it may possess other enzymes that influence steroidogenesis.

Animals↗
PubMed1992

Effects of K+ on the twitch and tetanic contraction in the sartorius muscle of the frog, Rana pipiens. Implication for fatigue in vivo.

The effects of increasing the extracellular K+ concentration on the capacity to generate action potentials and to contract were tested on unfatigued muscle fibers isolated from frog sartorius muscle. The goal of this study was to investigate further the role of K+ in muscle fatigue by testing whether an increased extracellular K+ concentration in unfatigued muscle fibers causes a decrease in force similar to the decrease observed during fatigue. Resting and action potentials were measured with conventional microelectrodes. Twitch and tetanic force was elicited by field stimulation. At pHo (extracellular pH) 7.8 and 3 mmol K+.L-1 (control), the mean resting potential was -86.6 +/- 1.7 mV (mean +/- SEM) and the mean overshoot of the action potential was 5.6 +/- 2.5 mV. An increased K+ concentration from 3 to 8.0 mmol.L-1 depolarized the sarcolemma to -72.2 +/- 1.4 mV, abolished the overshoot as the peak potential during an action potential was -12.0 +/- 3.9 mV, potentiated the twitch force by 48.0 +/- 5.7%, but did not affect the tetanic force (maximum force) and the ability to maintain a constant force during the plateau phase of a tetanus. An increase to 10 mmol K+.L-1 depolarized the sarcolemma to -70.1 +/- 1.7 mV and caused large decreases in twitch (31.6 +/- 26.1%) and tetanic (74.6 +/- 12.1%) force. Between 3 and 9 mmol K+.L-1, the effects of K+ at pHo 7.2 (a pHo mimicking the change in interstitial pH during fatigue) and 6.4 (a pHo known to inhibit force recovery following fatigue) on resting and action potentials as well as on the twitch and tetanic force were similar to those at pHo 7.8. Above 9 mmol K+.L-1 significant differences were found in the effect of K+ between pHo 7.8 and 7.2 or 6.4. In general, the decrease in peak action potential and twitch and tetanic force occurred at higher K+ concentrations as the pHo was more acidic. The results obtained in this study do not support the hypothesis that an accumulation of K+ at the surface of the sarcolemma is sufficiently large to suppress force development during fatigue. The possibility that the K+ concentration in the T tubules reaches the critical K+ concentration necessary to cause a failure of the excitation-contraction coupling mechanism is discussed.

Action Potentials↗
PubMed1988

The role of referential speech in sign learning by mentally retarded children: a comparison of total communication and sign-alone training.

We conducted two experiments to assess the role of referential speech during sign training in which the spoken words corresponding to signs were receptively known to the participants. An alternating treatments design was used to compare sign acquisition across two teaching conditions in which referents were presented either with or without the corresponding verbal label. During the first experiment, signs were taught concurrently; during the second experiment, signs within each of the respective conditions were taught in a serial fashion. In both experiments, signs taught by total communication were acquired faster than those taught by sign-alone training.

Child↗