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Biomedical subjects

M E Andrew

Publications and source records attributed to M E Andrew.

At least 37 records · Page 2Linked to original sources

Lowering the threshold for the diagnosis of gestational diabetes.

OBJECTIVE: Our purpose was to determine whether lowering the diagnostic threshold for gestational diabetes mellitus on 3-hour 100 gm oral glucose tolerance testing will select a population at risk for adverse perinatal outcome. STUDY DESIGN: In this retrospective study 434 patients with an abnormal 50 gm glucose screen result (> or = 140 mg/dl) underwent a standardized 3-hour oral glucose tolerance test. The results were stratified according to maternal weight and the criteria recommended by Sacks or Carpenter. Birth weight and rate of macrosomia were the primary perinatal outcome variables analyzed. RESULTS: Analysis of the data set stratified according to the Sacks criteria revealed results very similar to the Carpenter criteria data set. Patients who would have been newly diagnosed with gestational diabetes mellitus only if the lowered criteria were used (group 2) were older and heavier. No other variable comparisons achieved statistical significance. When the same patients were stratified according to prepregnancy weight, overweight patients were older, gained less weight during the third trimester, underwent cesarean section more often, and had higher cumulative maternal morbidity. Regression analysis showed that the degree of hyperglycemia did not predict macrosomia or influence birth weight, but prepregnant maternal body mass index was associated with macrosomia. CONCLUSIONS: Fetal macrosomia is influenced by maternal prepregnant body mass index. Lowering the glucose tolerance test threshold would result in overdiagnosis of gestational diabetes mellitus without improving perinatal outcome.

Birth Weight↗

Reflection as infiltration: learning in the experiential domain.

This paper discusses part of an ethnomethodological study of a short, post-registration course in communication in palliative care. The study describes the different perceptions, expectations and reflections of the participants and the facilitators as they engaged together in learning through role-play, simulated interviews with patients and discussion. The emotionally challenging nature of experiential teaching in palliative care appeared to present the facilitators of the course with a number of dilemmas. The facilitators' reflections upon these dilemmas appeared to lead them to develop a series of strategies in an attempt to resolve them. During the study it became clear that some aspects of these strategies were withheld from the participants. These strategies and the reasoning behind them are described together with the participants' response. The study demonstrates how the participants' reflections upon the facilitator-led exercises led them to infiltrate the strategies adopted by the facilitators. The purpose of these strategies and the significance of the participants' unearthing of them are interpreted within the conceptual framework of Schön's "reflective practitioner'. The findings are discussed in relation to current nurse education and the possible implications for curriculum planning and development.

Education, Nursing, Continuing↗

Fibrin clot lysis by tissue plasminogen activator (tPA) is impaired in plasma from pediatric patients undergoing orthotopic liver transplantation.

Large vessel thrombi can present life-threatening complications following orthotopic liver transplantation (OLT) in pediatric patients. We investigated the thrombolytic response to tissue plasminogen activator (tPA) of stored, pooled plasma (days 4-14 postoperatively) from 41 patients (mean age 4 years, 9 months) who underwent OLT at the Hospital for Sick Children, Toronto between 1986 and 1990. Trace-labeled fibrin clots were prepared by recalcifying 500-microliters aliquots of patient plasma spiked with 125I fibrinogen and then incubated at 37 degrees C in patient plasma in the presence or absence of tPA (0.1 or 0.3 mg/ml). At the end of the incubation period, the extent of clot lysis and concentrations of fibrinogen, plasminogen, and alpha 2 antiplasmin were determined. Pooled adult plasma was used as a control. Fibrin clot lysis in OLT plasma was significantly reduced compared with controls (P < 0.01). Initial concentrations of plasminogen were significantly reduced in OLT plasma. To determine if the low plasminogen levels limited the thrombolytic effect of tPA, we supplemented OLT plasma with purified plasminogen. Fibrin clots placed in OLT plasma containing adult levels of plasminogen showed a similar lytic response as adults. In summary, the reduced fibrinolytic response of OLT fibrin clots to tPA was due to low concentrations of plasminogen and corrected by plasminogen supplementation.

Adult↗

Fresh frozen plasma has no beneficial effect on the hemostatic system in children receiving L-asparaginase.

L-Asparaginase (ASP), a chemotherapeutic agent used in the treatment of children with acute lymphoblastic leukaemia (ALL), is linked to thromboembolic complications secondary to an acquired deficiency of antithrombin III (ATIII). Fresh frozen plasma (FFP) is used to prevent and/or treat thrombotic complications in these children. However, the effect of FFP on plasma concentrations of ATIII and biochemical markers of activation of coagulation has never been tested. In this study, FFP (20 ml/kg) was administered to eight children with ALL receiving ASP in the consolidation phase of their treatment. Plasma samples were drawn pre-infusion, and following infusion at 1, 24, and 48 hr. Prior to the FFP infusions, plasma concentrations of prothrombin, fibrinogen, alpha 2-macroglobulin, heparin cofactor II, protein C, and protein S were similar to levels in healthy children. Only plasma concentrations of ATIII were significantly decreased (0.55 U/ml). Following FFP infusions, there was no statistical or clinically important increase in plasma concentrations of any coagulation protein at any time point. Pre-infusion plasma concentrations of markers of endogenous thrombin generation (thrombin-antithrombin III complexes (TAT)) and activation of the fibrinolytic system in response to activation of the coagulation system (D-dimer levels) were significantly increased. However, FFP had no statistical or clinically important effect on concentrations of these markers. We conclude that FFP administration for the prevention and treatment of acquired ATIII deficiency secondary to ASP has no demonstrable benefit on plasma levels of coagulation proteins and is unlikely to be of clinical benefit.

Adolescent↗

Induction of rotavirus-specific cytotoxic T lymphocytes by vaccinia virus recombinants expressing individual rotavirus genes.

We determined the capacity of vaccinia virus recombinants expressing individual rotavirus genes to induce virus-specific cytotoxic T lymphocytes (CTLs) in mice. Mice were orally inoculated with vaccinia virus recombinants containing genes which encode rotavirus outer capsid proteins vp4 or vp7, single-shelled virus proteins vp1, vp2, or vp6, or rotavirus nonstructural proteins NS53, NS35, NS28, or NS26/NS12. We found that (i) the greatest frequencies of virus-specific CTLs were induced by vaccinia virus recombinants expressing vp7, (ii) transport of vp7 beyond the endoplasmic reticulum was not necessary for induction of CTLs, (iii) recombinants expressing vp7 induced CTLs which reacted with different rotavirus serotypes, and (iv) CTLs were induced among both intestinal and nonintestinal lymphocytes after oral inoculation. These findings may be relevant to vaccine strategies which utilize vectors expressing individual rotavirus genes.

Administration, Oral↗

Suprapubic bladder aspiration versus urethral catheterization in ill infants: success, efficiency and complication rates.

STUDY OBJECTIVE: To compare success rates, complications, and efficiency of suprapubic bladder aspiration with urethral catheterization in ill infants. DESIGN: Prospective, randomized clinical study. SETTING: The pediatric emergency department at the University of Mississippi Medical Center in Jackson. PARTICIPANTS: Convenience sample of infants under 6 months of age requiring an uncontaminated urine specimen for the evaluation of febrile illness, suspected urinary tract infection, or sepsis. Infants with wet diapers were excluded. INTERVENTIONS: Patients were randomized to undergo timed suprapubic bladder aspiration (performed by a physician and a nurse) or urethral catheterization (performed by two nurses). If suprapubic bladder aspiration was unsuccessful, urethral catheterization was performed immediately and the bladder was drained; emptying volume was recorded. All patients had a next-void "bag" urinalysis performed for post-procedure hematuria. RESULTS: Fifty patients underwent primary suprapubic bladder aspiration. The success rate (defined by obtaining at least 2 mL of urine) was 46%. Mean +/- SD time per successful suprapubic bladder aspiration was 16.73 +/- 7.73 seconds. Fifty patients underwent primary urethral catheterization. The success rate was 100%; the mean time required was 80.70 +/- 46.52 seconds. After failed suprapubic bladder aspiration, urethral catheterization was 100% successful, with a mean draining volume of 2.95 +/- 2.38 mL. No immediate problems were identified among any instrumented patients; later complications (next-void hematuria after either procedure, other visceral injury with suprapubic bladder aspiration) were not detected. CONCLUSION: Both suprapubic bladder aspiration and urethral catheterization afford the emergency physician low-risk access to uncontaminated urine in ill infants. Suprapubic bladder aspiration is less efficient in that it requires physician participation and failure rates are higher. These data suggest that successful suprapubic bladder aspiration is primarily dependent on the volume of urine in the bladder; thus, in the ill or febrile ED infant who may be dehydrated, the likelihood of success decreases. The authors recommend that ED nursing and physician staff become comfortable with performing urethral catheterization on infants.

Drainage↗

Body mass index and blood pressure in Korean men and women: the Korean National Blood Pressure Survey.

AIMS AND METHODS: The association between body mass index (BMI) and blood pressure is well known in relatively obese populations. The purpose of the present study was to investigate the relationship between BMI and blood pressure in a lean population. Through cluster sampling, individuals aged > 30 years in 190 out of 154,082 districts were selected for study. Among 25,567 eligible individuals, measurements of blood pressure and BMI were made in 22,354. RESULTS: The BMI for males was 22.8 +/- 2.7 kg/m2 and for females was 23.4 +/- 3.2 kg/m2 (means +/- SD). Over a BMI range from 16 to 31 kg/m2 the relationships between BMI and systolic and diastolic blood pressure were almost linear. Over the BMI range 25-31 kg/m2 (overweight-to-obese) each BMI unit was associated with a difference of 1.0 mmHg in diastolic blood pressure. Over the BMI range 16-25 kg/m2 (normal-to-lean) each BMI unit was associated with a difference of 0.89 mmHg in diastolic blood pressure. CONCLUSION: We conclude that a strong association between BMI and blood pressure exists for lean as well as for obese subjects.

Adult↗

Clinical characteristics of children with hereditary hemolytic anemias and aplastic crisis: a 7-year review.

We reviewed the clinical courses of children < or = 16 years of age with hereditary hemolytic anemias who were admitted to the University of Mississippi Medical Center for aplastic crisis. Constitutional signs, gastrointestinal complaints, and headache were the most frequent findings. Statistically significant decreases in hemoglobin levels, hematocrit, and reticulocyte counts, but not total white blood cell or platelet counts, were found on admission when compared to other times of determination. For 27 of 49 patients, IgM antibody determinations to human parvovirus (B19) were available, and 15 (56%) had positive values. We conclude that erythroid (but not other) blood cell lines are helpful in establishing a clinical diagnosis, and that both acute and convalescent titers are necessary to assess the immune response to the infection. Physicians should continue to search for agents other than B19 parvovirus in patients in whom B19 antibodies cannot be found.

Adolescent↗

Effect of disease and chemotherapy on hemostasis in children with acute lymphoid leukemia.

PURPOSE: We sought to determine the effect of disease and combination chemotherapy on the hemostatic system in children with acute lymphoid leukemia (ALL). PATIENTS AND METHODS: We conducted a prospective study of children newly diagnosed with ALL. Plasma samples were obtained at four time points: at diagnosis before therapy, 5 days after administration of L-asparaginase alone, after the remission induction program, and at completion of the consolidation phase. Plasma levels of 21 hemostatic proteins were measured. The amount of thrombin generated following activation with an APTT reagent was quantitated. RESULTS: At diagnosis there were significant elevations in factors VIII, IX, von Willebrand, alpha 2-macroglobulin and protein S. In contrast, there were significant reductions in protein C, prekallikrein, and factors XIIIA and XIIIS. L-asparaginase treatment alone decreased concentrations of 11 proteins, with antithrombin III being affected to the greatest extent. After multiagent chemotherapy, not including L-asparaginase, concentrations of most proteins increased to or above baseline. At completion of consolidation therapy, which included weekly L-asparaginase administration, concentrations of most proteins were decreased compared with baseline values. The amount of thrombin generated following activation with an APTT reagent was similar to adults. CONCLUSION: Plasma concentrations of coagulation proteins are affected by disease (ALL) alone and by combination chemotherapy with or without L-asparaginase. There is no impairment of in vitro capacity to generate thrombin. L-asparaginase alone caused a decrease in almost all proteins; however, ATIII was affected to the greatest extent.

Adolescent↗

Protective immunity to rotavirus-induced diarrhoea is passively transferred to newborn mice from naive dams vaccinated with a single dose of a recombinant adenovirus expressing rotavirus VP7sc.

VP7sc is a novel rotavirus antigen engineered for presentation at the cell surface. Several recombinant viruses were constructed in which VP7sc was inserted into the E3 region of the human type 5 adenovirus (Ad5) genome and expression and transport of the antigen was monitored in cultured 293 cells. The recombinant virus showing the greatest level of expression (Ad5/7.4) was then used to determine whether antibodies to VP7sc could be induced in a nonhuman host. BALB/c and CBA/H mice were inoculated with Ad5/7.4 by iv, ip, oral and intranasal routes and serum antibody levels were assayed by ELISA. All vaccinated animals seroconverted but, depending on the route of vaccination, not all animals showed a significant secondary response following re-inoculation. The ability of Ad5/7.4 to induce protective immunity in mice was also examined using several vaccination regimes. A single dose of Ad5/7.4 given intranasally to dams not previously exposed to rotavirus was sufficient to induce immunity which could be passively transferred to protect suckling neonates. Recombinant adenoviruses expressing protective antigens therefore may provide an alternative to the use of attenuated rotaviruses in the development of a vaccine against gastroenteritis.

Adenoviruses, Human↗

Development of a computer application for headache diagnosis: the Headache Diagnostic System.

A computer-assisted decision support system for headache classification and diagnosis is presented. The system provides: structured headache data collection, automated data quality control and management, and automated headache classification. The system is based upon headache classification and diagnostic criteria recently developed by the International Headache Society. Development, logical structure and validation of the system are discussed. The system is shown to provide a general improvement in headache classification reliability and has utility for validation and improvement of present headache classification criteria.

Adult↗

Rotavirus VP6 modified for expression on the plasma membrane forms arrays and exhibits enhanced immunogenicity.

The major inner capsid protein of rotavirus is VP6, a 42-kDa polypeptide that forms the icosahedral surface of the rotavirus single-shelled particle. A chimeric form of VP6 (VP6sc) was constructed containing an upstream leader sequence derived from the influenza virus hemagglutinin and a downstream membrane-spanning (anchor) domain from a mouse immunoglobulin gene. When VP6sc was expressed in cells using a recombinant vaccinia virus, the protein was transported, glycosylated, and anchored in the plasma membrane as a trimer with the major domains of the protein orientated externally. Immunofluorescence and immunolabeling with colloidal gold indicated that VP6sc also localized in patches on the cell surface; electron microscopy revealed that the protein assembled into two-dimensional arrays which exhibited the same periodicity as the paracrystalline arrays formed by purified (viral) VP6. Mice inoculated with a recombinant vaccinia virus that expressed VP6sc produced rotavirus-specific antibodies at a titer 10 times higher than that achieved when wild-type, intracellular VP6 was delivered in the same way. Presentation at the cell surface therefore may represent a general method for enhancing the immunogenicity of rotavirus proteins.

Animals↗

Vaccinia-rotavirus VP7 recombinants protect mice against rotavirus-induced diarrhoea.

Recombinant vaccinia viruses expressing wild type intracellular VP7 (VP7wt) from rotavirus SA11 or VP7sc, a cell surface-anchored variant, boosted antibody titres in SA11-immune mice. Pups born to these mice were protected from diarrhoea following challenge with SA11. In rotavirus-naive mice, two immunizations with recombinant vaccinia virus expressing VP7sc stimulated protective immunity that could be transferred to pups, whereas viruses expressing VP7wt did not stimulate protective immunity. Recombinant vaccinia viruses expressing intracellular or cell surface-anchored VP6, the rotavirus group-reactive antigen from the inner capsid, did not stimulate protective immunity. These experiments demonstrate that a live viral vector expressing cell surface anchored VP7 may represent a strategy for the development of safe, effective vaccines against rotavirus-induced diarrhoea.

Animals↗

Biological effects of recombinant vaccinia virus-expressed interleukin 4.

Recombinant vaccinia viruses expressing murine interleukin 4 (IL-4), either alone or together with interleukin 2 (IL-2) or gamma interferon (gamma-IFN), were constructed. Unlike IL-2, IL-4 expressing viruses were not cleared from immunodeficient mice and the mice died. As they died more rapidly than immunodeficient mice inoculated with a control virus, it appeared that IL-4 contributed to their death and the IL-4 mediated toxicity was confirmed in normal immunocompetent mice. The toxicity was reversed by co-expression of either IL-2 or gamma-IFN, probably due to virus clearance and therefore lower levels of circulating IL-4. Vaccinia virus-expressed IL-4 did not increase antibody or natural killer cell levels and caused a slight decrease in cytotoxic T lymphocyte levels.

Animals↗

Relocation of antigens to the cell surface membrane can enhance immune stimulation and protection.

The major outer capsid glycoprotein of rotaviruses, VP7, is normally synthesized and directed to the ER, where it is required for virus assembly. By substituting a foreign signal sequence for the VP7 signal peptide, a secreted form of VP7 with an authentic amino terminus was produced. Secreted VP7 was further modified by the addition of a transmembrane anchor and cytoplasmic domain to its C-terminus. When the novel chimeric protein was expressed in transfected cells it became anchored in the cell surface membrane. The antigenicity of the chimeric protein was compared with that of the intracellular form of VP7 using recombinant vaccinia viruses to deliver the antigens in vivo. The novel antigen produced enhanced stimulation of both B and T lymphocytes of the immune system, and in mice it was able to induce protection against rotavirus-induced diarrhoeal disease. Other secreted and intracellular antigens show a similar improved level of antigenicity as a result of their relocation to the cell surface. Surface localization may therefore have general utility in the development of recombinant subunit vaccines.

Animals↗

Intraosseous infusion of resuscitative fluids and drugs: long-term effect on linear bone growth in pigs.

We studied the effects of intraosseous (IO) infusion of a standard fluid bolus and resuscitative drugs on long-term bone growth and epiphyseal closure in the "pediatric" swine model. Eighteen weanling pigs were randomly assigned to six groups as follows: three animals received two normal saline boluses, 20 mL/kg IO over 20 minutes; three received sodium bicarbonate, 1 mEq/kg IO; three received a 10% sodium bicarbonate infusion IO at maintenance rate over 1 hour; three received epinephrine 1:10,000, 0.1 mL/kg IO; three received an epinephrine infusion IO at 1 microgram/kg/min for 1 hour; and three received a dopamine infusion IO at 10 micrograms/kg/min for 1 hour. All infusions were given in the left hindleg; the right hindleg was used as a control. Lateral radiographs of the hind extremities were obtained at the beginning of the study and at 1 and 3 months after infusion. Linear radiographic measurements of the infused and control tibias were compared. At 6 months after infusion, the tibias were harvested, measured directly, and radiographed to determine the degree of epiphyseal closure. Analysis of variance for the first 3 months' data yielded a nonsignificant time-by-treatment interaction (P = .84) and a nonsignificant main effect for time (P = .22). Separate analysis of the direct measurements taken at 6 months revealed no difference in growth between experimental and control tibias. In addition, no radiographic difference in epiphyseal closure was noted between the two groups at the conclusion of the study, nor were any structural defects discovered. Intraosseous infusion of fluids and resuscitative drugs does not adversely affect subsequent bone growth and development in the swine model.

Animals↗

Important curriculum content for baccalaureate allied health programs: a survey of deans.

The purpose of this study was to assist deans of baccalaureate-level schools of allied health professions to come to consensus on knowledge and skills that graduates should have over and above what is required for professional accreditation and credentialing, and prerequisite or cognate courses that may be utilized to develop them. An adaptation of the Delphi method was used in 1990-1991 to survey the deans of 74 institutional members of the Association of Schools of Allied Health Professions (ASAHP) offering programs at the bachelor's degree level. Three rounds of questionnaires were completed. The study concluded that there was consensus among the 54 deans who responded to the third questionnaire that 19 items of knowledge and skill are important for allied health students, and that 14 courses are important for the development of this knowledge and these skills.

Allied Health Occupations↗

Effects of vaccinia virus-expressed interleukin 2 on the immune system of sublethally irradiated mice.

Vaccinia virus that expressed interleukin 2 (IL 2) was cleared from immunodeficient irradiated mice more efficiently than virus that did not express interleukin 2. These results extend the previously observed protection from nude mice to another model of immunodeficiency. No antibody or cytotoxic T lymphocyte response could be detected in sublethally irradiated mice that had been inoculated with IL 2-expressing vaccinia virus, but levels of splenic natural killer cell activity were elevated. Sublethally irradiated mice that had recovered from IL 2-plus hemagglutinin-expressing vaccinia virus were partially protected against both influenza virus and vaccinia virus. These results indicate that vaccinia virus-expressed IL 2 mediates clearance of primary viral infection via a mechanism that does not involve antibody or cytotoxic T lymphocytes. They also indicate that inclusion of lymphokine genes in live recombinant viral vaccine vectors may increase vaccine safety.

Administration, Intranasal↗