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Biomedical subjects

K Sullivan

Publications and source records attributed to K Sullivan.

At least 73 records · Page 4Linked to original sources

An economic survey of the emerging tissue engineering industry.

The contemporary scope of worldwide tissue engineering research and development was estimated by totaling the relevant annual spending and other economic parameters of firms involved the field. Operating expenses allocated to tissue engineering in 1997 exceed $450 million and fund the activities of nearly 2,500 scientists and support personnel. Growth rate is 22.5% per annum. Most activity is centered in the United States. Government spending in this field represents <10% of the total. The aggregate capital value of start-ups that have gone public was approximately $1.7 billion as of January 1, 1998; total capital value of all firms and business units in the field was estimated to be roughly $3.5 billion. The level of investment and valuation represents a remarkable act of faith in the future of a technology yet to produce its first significant revenue-generating product.

Artificial Organs↗

The Pediatric Radiofrequency Ablation Registry's experience with Ebstein's anomaly. Pediatric Electrophysiology Society.

INTRODUCTION: Abnormal anatomy and complex electrophysiology in patients with Ebstein's anomaly of the tricuspid valve may confound attempts at radiofrequency ablation (RFA). METHODS AND RESULTS: Data for 65 pediatric Ebstein's patients (9.8+/-5.4 years, 4 months to 20 years; 39+/-25 kg, 5.1 to 108 kg) were obtained from the Pediatric Radiofrequency Ablation Registry. The degree of tricuspid regurgitation (DOTR) and the degree of Ebstein's anomaly were assessed with echocardiography/Doppler. Leading indications were drug refractoriness (24 [37%] of 65 patients) and life-threatening arrhythmia (14 [22%] of 65 patients). For the 65 patients, 82 typical (nondecremental) accessory pathways (APs) (62% right free wall, 34% right septal, and 4% left sided), 17 other supraventricular tachycardias (1 ectopic atrial, 7 AV reentry, 5 Mahaim, and 4 intra-atrial reentry tachycardias), and 1 ventricular mechanism were mapped. Thirty-four (52%) of 65 patients had a single AP (21 right free wall, 10 septal, and 3 left); 19 (29%) of 65 patients multiple APs; 6 (9%) of 65 patients a single AP plus a non-AP mechanism; and 6 (9%) of 65 patients non-AP mechanism(s) only. RFA acute success rates and recurrence rates for right free wall, right septal, and other mechanisms were 79%/32%, 89%/29%, and 75%/27%. Mild DOTR and a body surface area (BSA) < or = 1.7 m2 independently predicted a better acute success rate. BSA < or = 1.7 m2 also predicted long-term success. CONCLUSION: In this patient subset, life-threatening arrhythmias and multiple electrophysiologic mechanisms are commonly encountered during RFA. Mild DOTR and a BSA < or = 1.7 m2 predict a higher acute success rate. While acute success rates are relatively high, recurrence is frequent.

Adolescent↗

Do pediatric intensivists and radiologists concur on the interpretation of chest radiographs?

BACKGROUND: Therapeutic decisions in the pediatric intensive care unit are made by pediatric intensivists (PI) based on their interpretation of chest radiographs before the formal interpretation by a pediatric radiologist (PR). This study was designed to determine the adequacy of chest radiograph interpretations by pediatric intensivists and the effects on patient care. The PI recorded their chest radiograph interpretations, documenting support devices and thoracic abnormalities. Concordance and discordance were determined by the pediatric pulmonologist who was not involved in the care of the patient by comparing the interpretations of the PI and PR. Clinically significant discordance was defined as interpretations by the radiologist that differed to those from the PI that may have required therapeutic intervention. RESULTS: The evaluation of 291 chest radiographs demonstrated an overall concordance rate of 82.5% (240 out of 291; P < 0.05). There was no significant difference in the ability of critical care medicine physicians to identify atelectasis, infiltrates, pleural effusions, or airleaks (P > 0.05). Support devices were correctly identified in 100% of the cases. Discordant interpretations included 20 that were clinically significant, 17 insignificant findings and 14 films over-interpreted by the PI. A chart review of the patients with discordant findings revealed only one finding that required an alteration in therapy. CONCLUSIONS: These findings demonstrate significant agreement between the interpretation of chest radiographs by PI and PR in selected clinical situations. These data support the current practice of the PI making therapeutic decisions based on their interpretations of chest radiographs.

Journal Article↗

Alterations in receptor activation and divalent cation activation of agonist binding by deletion of intracellular domains of the glucagon receptor.

Deletion of residues 252-259 within the putative second intracellular loop of the human glucagon receptor results in a protein with high affinity for glucagon but with attenuated agonist activation of adenylyl cyclase. The Delta252-259 mutant has 4-fold higher affinity for glucagon than does the wild type receptor. The nonhydrolyzable GTP analog, guanosine 5'-(beta, gamma-imido)triphosphate (Gpp(NH)p), inhibits binding of 125I-glucagon to the wild type receptor but not to the Delta252-259 mutant. Divalent cations such as MgCl2 and CaCl2 stimulate the binding of 125I-glucagon to the wild type receptor by increasing glucagon affinity. The rate of dissociation of 125I-glucagon is decreased 4-fold by MgCl2 and increased 6-fold by Gpp(NH)p. However, divalent cations do not affect the binding of 125I-glucagon to the Delta252-259 mutant. The rate of dissociation of 125I-glucagon from the Delta252-259 mutant protein is equivalent to the rate of dissociation from the wild type receptor in the presence of MgCl2. These data suggest that at least three conformations of the glucagon receptor can exist in the membrane based on their differing affinities for 125I-glucagon. Deletion of residues 252-259 appears to lock the protein in the conformation promoted by divalent cations and prevents the protein from normal coupling to Gs.

Amino Acid Sequence↗

Effects of chronic lithium treatment on retinal electrophysiologic function.

Some hypotheses suggest that lithium produces its therapeutic effect by reducing sensitivity to light at the level of the retina. In humans, acute administration of lithium is associated with a reduction in retinal light sensitivity. To determine whether similar retinal light sensitivity changes occur with chronic use, we studied 24 euthymic bipolar patients on chronic lithium treatment and 21 age- and sex-matched normal comparison subjects using electroretinography (ERG) and electro-oculography (EOG). No significant differences were found in ERG b-wave amplitudes or implicit times, or in EOG ratios, between the two groups. We conclude that chronic lithium use is not associated with differences in retinal light sensitivity when bipolar patients are compared to normal comparison subjects, and that there is no evidence for retinal toxicity with long-term lithium treatment.

Adult↗

Comparison of quantitative echocardiography with endomyocardial biopsy to define myocardial rejection in pediatric patients after cardiac transplantation.

Endomyocardial biopsy is the gold standard for determining rejection; however, no echocardiographic indexes have been widely accepted as indicators of rejection. The stress-velocity relation of corrected velocity of circumferential fiber shortening to wall stress is a preload independent index of contractility that incorporates afterload and has been shown to distinguish a decreased velocity caused by excess afterload from that caused by decreased contractility. Wall stress has not been previously reported as a determinant of rejection. We report a prospective double-blind study of pediatric cardiac transplant patients comparing biopsy and quantitative systolic echocardiographic data. Thirty-two pediatric patients underwent 67 biopsies. At the time of catheterization, an echocardiographic evaluation was performed. Standard measurements of systolic function were collected and left ventricular (LV) fractional shortening, LV volume, LV mass, velocity of circumferential fiber shortening, and estimated end-systolic wall stress were calculated. In evaluating echocardiographic data of patients with and without biopsy-proven rejection, we were unable to identify any significant correlation between any systolic echocardiographic parameter and rejection. We conclude that: (1) the stress-velocity relation does not detect myocardial rejection; and (2) neither LV fractional shortening, LV volume, nor LV mass detect rejection; and (3) central venous pressure influence wall stress values significantly.

Adolescent↗

Which tests do neuropsychologists use?

A nationwide survey of accredited neuropsychologists in Australia was conducted to examine test use. Clinicians were asked to list the tests they give most often. Results are expressed as endorsement frequencies for tests. Comparisons with international surveys of test use are provided. Suggestions for clinicians and others concerned with test use are included to demonstrate how survey results can be used to improve neuropsychological services.

Australia↗

Spiral computed tomography for staghorn calculi.

OBJECTIVES: To assess the utility of spiral computed tomography (CT) with three-dimensional reconstruction for preoperative planning of percutaneous nephrostolithotomy in patients with complex branched calculi (full staghorns). METHODS: Patients with complex branched stones were imaged with spiral CT with three-dimensional reconstruction. These images were compared with standard imaging modalities, including excretory urography and plain radiographs, for planning percutaneous access for nephrostolithotomy. The utility of the scan was evaluated. RESULTS: Ten patients with branched calculi were studied. Anatomic abnormalities were present in 5 patients. Excellent three-dimensional images were obtained in all patients without any complications related to the study. In 1 patient with multiple calculi in a horseshoe kidney, the three-dimensional image indicated a branched stone. The spiral CT scan was not helpful in directing percutaneous access in any patient. In a single patient, residual fragments noted during nephrostolithotomy were located by reference to the spiral CT scan. CONCLUSIONS: Spiral CT scans with three-dimensional reconstruction provide three-dimensional imaging of branched renal calculi. This modality provides minimal additional information over that obtained from standard radiographic studies for guiding nephrostolithotomy and cannot be recommended as a routine preoperative study. It was helpful in 1 patient to locate a residual fragment.

Adult↗

When 3-year-olds pass the appearance--reality test.

Sixty-eight 3-year-olds received a standard appearance-reality task along with either a trick task, in which the appearance question was placed in the context of a deceptive game, or a reduced information processing task, in which a dual object (e.g., a sponge-rock) was presented along with an object that matched the dual object's identity (a sponge) and one that matched the dual object's appearance (a rock). Children were more likely to pass either the trick or reduced information processing task and fail the standard than the reverse. Thus, 3-year-olds can grasp the distinction between appearance and reality (a) when their goal is to trick someone, which may prime them to think about the other's mental state, and (b) when they do not need to held conflicting object identities in mind at the same time.

Child Development↗

A high observed substitution rate in the human mitochondrial DNA control region.

The rate and pattern of sequence substitutions in the mitochondrial DNA (mtDNA) control region (CR) is of central importance to studies of human evolution and to forensic identity testing. Here, we report a direct measurement of the intergenerational substitution rate in the human CR. We compared DNA sequences of two CR hypervariable segments from close maternal relatives, from 134 independent mtDNA lineages spanning 327 generational events. Ten substitutions were observed, resulting in an empirical rate of 1/33 generations, or 2.5/site/Myr. This is roughly twenty-fold higher than estimates derived from phylogenetic analyses. This disparity cannot be accounted for simply by substitutions at mutational hot spots, suggesting additional factors that produce the discrepancy between very near-term and long-term apparent rates of sequence divergence. The data also indicate that extremely rapid segregation of CR sequence variants between generations is common in humans, with a very small mtDNA bottleneck. These results have implications for forensic applications and studies of human evolution.

Animals↗

Predictors of change in insulin sensitivity during glucocorticoid treatment.

Glucocorticoid induced alterations in carbohydrate metabolism can result in hyperglycemia. We evaluated changes in carbohydrate metabolism produced by four days of prednisone (20 mg PO TID) measuring insulin sensitivity, basal glucose, basal insulin and first phase insulin release (FPIR). We correlated these measures of carbohydrate metabolism with changes in free fatty acids and lactate levels both of which have been reported to be possible mediators of insulin sensitivity. Insulin sensitivity decreased by 64% (p = 0.002), basal insulin levels increased 50% (p = 0.026), FPIR tripled (p = 0.064) while fasting glucose levels increased significantly but remained normal. Basal FFAs levels increased (p = 0.045) while lactate levels did not change significantly, and neither predicted changes in SI. Basal levels of SI and FPIR were found to be independent predictors of change in insulin sensitivity and together explained 83% of the change in insulin sensitivity produced by short term treatment with prednisone.

Adult↗

The 22q11.2 deletion: screening, diagnostic workup, and outcome of results; report on 181 patients.

A submicroscopic deletion of chromosome 22q11.2 has been identified in the majority of patients with the DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and in some patients with isolated conotruncal cardiac anomalies, Opitz G/BBB syndrome, and Cayler cardiofacial syndrome. We have evaluated 181 patients with this deletion. We describe our cohort of patients, how they presented, and what has been learned by having the same subspecialists evaluate all of the children. The results help define the extremely variable phenotype associated with this submicroscopic deletion and will assist clinicians in formulating a management plan based on these findings.

Abnormalities, Multiple↗

The Multidimensional Anxiety Scale for Children (MASC): factor structure, reliability, and validity.

OBJECTIVE: To describe the history, factor structure, reliability, and validity of the Multidimensional Anxiety Scale for Children (MASC). METHOD: In two separate school-based population studies, principal-components factor analysis was used, first, to test a theory-driven factor structure, and second, to develop an empirically derived factor structure for the MASC. In a separate study using a clinical population, test-retest reliability at 3 weeks and 3 months, interrater concordance, and convergent and divergent validity were examined. RESULTS: The final version of the MASC consists of 39 items distributed across four major factors, three of which can be parsed into two subfactors each. Main and subfactors include (1) physical symptoms (tense/restless and somatic/autonomic), (2) social anxiety (humiliation/rejection and public performance fears), (3) harm avoidance (perfectionism and anxious coping), and (4) separation anxiety. The MASC factor structure, which presumably reflects the in the vivo structure of pediatric anxiety symptoms, is invariant across gender and age and shows excellent internal reliability. As expected, females show greater anxiety on all factors and subfactors than males. Three-week and 3-month test-retest reliability was satisfactory to excellent. Parent-child agreement was poor to fair. Concordance was greatest for easily observable symptom clusters and for mother-child over father-child or father-mother pairs. Shared variance with scales sampling symptom domains of interest was highest for anxiety, intermediate for depression, and lowest for externalizing symptoms, indicating adequate convergent and divergent validity. CONCLUSION: The MASC is a promising self-report scale for assessing anxiety in children and adolescents.

Adolescent↗

Bridging the care continuum for open heart surgery patients.

A pilot program followed patients who were recovering from coronary artery bypass graft procedures. A cardiac surgery nurse visits patients in their homes to provide physical assessments, reinforce discharge teaching and answer questions. Because of the pilot's success, the program was integrated with the transitional open heart unit.

Aftercare↗

The logic of tax-based financing for health care.

Employment-based health insurance faces serious problems. For the first time, the number of Americans covered by such health insurance is falling. Employers strongly oppose the employer mandate approach to extending health insurance. Employment-based financing is regressive and complex. Serious debate is needed on an alternative solution to financing health care for all Americans. Taxation represents a clear alternative to employment-based health care financing. The major criterion for choosing a tax is equity, with simplicity a second criterion. An earmarked, progressive individual income tax is a fair and potentially simple tax with which to finance health care. The political feasibility of such a tax is greater than that of employer mandate legislation.

Health Benefit Plans, Employee↗

Canadian atrial fibrillation anticoagulation study: were the patients subsequently treated with warfarin? Canadian Atrial Fibrillation Anticoagulation Study Group.

OBJECTIVE: To determine the effect of the results of clinical trials on the behaviour of patients and physicians, the authors ascertained the proportion of patients participating in the Canadian Atrial Fibrillation Anticoagulation (CAFA) study who started or continued warfarin therapy at the end of the study and identified factors affecting the decision to use or not use warfarin. The CAFA study was a double-blind, randomized, placebo-controlled, multicentre study to evaluate the efficacy of warfarin in preventing stroke among patients with nonrheumatic atrial fibrillation. Recruitment and follow-up were stopped early because two other similar studies had shown a decrease in the rate of stroke among patients treated with warfarin. DESIGN: Mail survey 21 months after the end of the study. PARTICIPANTS: The personal physicians of 336 patients who had participated in the CAFA study. OUTCOME MEASURES: Type of antithrombotic therapy the patients had received since the CAFA study ended for patients who were not receiving warfarin, the reasons they were not. RESULTS: Questionnaires concerning 254 (76%) of the patients who had participated in the study were returned. Since the end of the CAFA study, 153 (60%) of these patients had been treated continually with warfarin, 14 (6%) had been treated with warfarin but had subsequently stopped taking it, 59 (23%) had taken acetylsalicylic acid (ASA) continually, 5 (2%) had been taking ASA but had subsequently stopped taking it, and 23 (9%) had not taken either drug. The responding physicians stated that 58 (67%) of the patients who were not treated with warfarin did not wish to take the drug. The patients who had received warfarin during the CAFA trial were more likely to be treated with warfarin after the trial (75%) than were those who had received a placebo (56%) (p = 0.001). The probability of the patients' being treated with warfarin also depended on which study centre they had been treated in (p = 0.001). CONCLUSIONS: Of the patients in the CAFA study for whom questionnaires were received, only 167 (66%) had been treated with warfarin after the end of the study. The patients were more likely to have been treated with warfarin after the study if they had received warfarin during the study. The positive results of clinical trials, on their own, are not enough to fully change the behaviour of patients and physicians.

Aged↗

Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation.

Patients successfully treated with a marrow transplant often have concerns about fertility and pregnancy. This study was performed to determine pregnancy outcome among patients who had received high-dose chemotherapy alone or with total-body irradiation (TBI) and marrow transplantation for aplastic anemia or hematologic malignancy. Records of 1,326 postpubertal and 196 prepubertal patients currently more than 12 years of age after marrow transplant in Seattle from August 1971 to January 1992 were reviewed to determine the patients with normal gonadal function and pregnancies. Among 708 postpubertal women, 110 recovered normal ovarian function and 32 became pregnant. In addition, nine formerly prepubertal girls with normal gonadal function became pregnant. Among 618 postpubertal men, 157 recovered testicular function and partners of 33 became pregnant. An additional two formerly prepubertal men had partners who became pregnant. Forty-one female patients and partners of 35 male patients had 146 pregnancies after transplant. All 76 patients responded to a questionnaire requesting pregnancy history, outcome, infant birth weight, and congenital anomalies information for all clinically recognized pregnancies. There were 115 live births among 146 (79%) pregnancies. Spontaneous abortion terminated four of 56 (7%) pregnancies for 28 female cyclophosphamide (CY) recipients and six of 16 (37%) pregnancies for 13 TBI recipients (P = .02). Partners of 28 male CY recipients had four of 62 (6.4%) pregnancies terminate with spontaneous abortion, but there were no spontaneous abortions among eight pregnancies of five TBI recipients' partners. Preterm delivery occurred for eight of 44 (18%) and five of eight (63%) live births for 24 CY and eight TBI female recipients (P = .01). This 25% incidence among all female patient pregnancies is higher than the expected incidence of 8% to 10% (P = .0001). The 13 preterm deliveries resulted in 10 low birth weight ([LBW] 1.8 to 2.24 kg) and three very low birth weight ([VLBW] < or = 1.36 kg) infants, for an overall incidence of 25%, which is higher than the expected incidence of 6.5% for the general population (P = .0001). Twelve of the 13 premature infants survive. Congenital anomalies were seen among two of 52 (3.8%) live-born infants of female and six of 63 (9.5%) live-born infants of male patients, which is not different from the 13% of single congenital anomalies reported for the general population. These data demonstrate that clinically recognized pregnancies among women who have received a marrow transplant incorporating TBI are likely to be accompanied by an increased risk of spontaneous abortion. Pregnancies among all women who received a marrow transplant are likely to be accompanied by preterm labor and delivery of LBW or VLBW babies who do not seem to be at an increased risk of congenital anomalies. However, determination of possible adverse effects of parental exposure to high-dose alkylating agents with or without TBI on children born posttransplant requires longer, additional follow-up.

Adult↗