Search PubMed⌕ Search

Biomedical subjects

M Andrew

Publications and source records attributed to M Andrew.

At least 163 records · Page 9Linked to original sources
PubMed1992

Abnormalities in von Willebrand factor and antithrombin III after cardiopulmonary bypass operations for congenital heart disease.

In patients with congenital heart disease two poorly understood postoperative complications are pulmonary hypertensive crises after repair of large atrioventricular or ventricular septal defects and right atrial and pulmonary thrombi after the Fontan operation. In this study we assessed whether cardiopulmonary bypass in these patients is associated with the release of agents that might induce platelet aggregation and vasoconstriction, such as biologically active von Willebrand factor and platelet-activating factor. In addition, we measured levels of anticoagulants such as antithrombin III and proteins C and S. Three groups of patients with congenital heart disease undergoing cardiopulmonary bypass were monitored through the perioperative period for secundum atrial septal defects, large atrioventricular or ventricular septal defects, and tricuspid atresia or univentricular heart (Fontan candidates). Control values were obtained from age-matched patients; patients requiring major noncardiac operations and those with cardiac disease not requiring cardiopulmonary bypass were also studied. After cardiopulmonary bypass in all three groups biologic activity of von Willebrand factor increased markedly in the immediate and early postoperative periods compared with preoperative values, whereas antithrombin III values were decreased. Platelet-activating factor was detected in only two patients with congenital heart disease, both in the early postoperative period. In contrast, patients who did not have cardiopulmonary bypass did not show these abnormalities. All measured parameters normalized at late follow-up (6 to 18 months after operation). Although cardiopulmonary bypass in these patients resulted in increased von Willebrand factor activity and decreased antithrombin III, changes that may predispose the patient to platelet aggregation and thrombus formation, absolute values in individual patients alone were not predictive of pulmonary hypertensive crises or detectable thrombi. This suggests that these hematologic abnormalities may contribute to but are not by themselves a cause of morbidity in the early postoperative period. Moreover, the increased von Willebrand factor biologic activity seen postoperatively in patients with congenital heart disease suggests that use of synthetic vasopressin may be ineffective and potentially detrimental.

Antithrombin III↗
PubMed1991

Alpha-2-macroglobulin may provide protection from thromboembolic events in antithrombin III-deficient children.

Antithrombin III (ATIII) deficiency has been implicated in adults as a predisposing factor to thrombosis; however, thromboembolic complications are rare in children with the same deficiency. We hypothesized that because of the elevated levels of plasma alpha-2-macroglobulin (alpha 2M) throughout childhood, plasmas of ATIII-deficient children inhibit thrombin more efficiently than those of ATIII-deficient adults. In total, 14 ATIII-deficient adults (ages 25 to 46 years), 13 ATIII-deficient children (ages 2 to 13 years), 9 normal children (ages 3 to 15 years), and 16 normal adults were studied. We measured thrombin inhibition in these plasmas, as well as the contributions of ATIII, alpha 2M, and heparin cofactor II (HCII) as thrombin inhibitors in each plasma. 125I-alpha-thrombin, 25 nmol/L, was added to each plasma (defibrinated with Arvin at 37 degrees C), and 90 seconds later the free thrombin and thrombin-inhibitor complexes were quantitated after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography, and densitometric scanning. Plasma from ATIII-deficient adults inhibited significantly less thrombin (12.8 +/- 0.6 nmol/L) than both normal adults (16.1 +/- 0.3 nmol/L, P less than .01), normal children (15.7 +/- 0.4 nmol/L, P less than .01), or ATIII-deficient children (15.5 +/- 0.3 nmol/L, P less than .01). There was no significant difference between the total concentration of thrombin inhibited by ATIII-deficient children and either normal adult or normal children groups. In addition, plasmas of ATIII-deficient children inhibited thrombin significantly more efficiently than plasma of ATIII-deficient adults (P less than .01). In the ATIII-deficient patients there was a significant correlation between the alpha 2M level and ability to inhibit thrombin (P less than .01), but no correlation between either ATIII or HCII levels and thrombin inhibition. On the addition of heparin (0.4 U/mL) to plasma, all four types of plasma inhibited thrombin to the same extent. Although ATIII was the predominant inhibitor in all heparinized plasmas, HCII inhibited more thrombin in the ATIII-deficient patients than in normal patients (2.8 +/- 0.3 v 1.2 +/- 0.2 nmol/L, P less than .01). We hypothesize that the lower risk of thromboembolic complications in ATIII-deficient children may be due in part to the protective effect of elevated alpha 2M levels during childhood.

Adolescent↗
PubMed1991

The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study.

In order to determine whether an association exists between antiphospholipid antibodies (APLA) and thromboembolic events in patients with systemic lupus erythematosus (SLE), we performed a cross-sectional study of consecutive unselected SLE patients. The occurrence of previous thromboembolic events was determined by investigators blinded to the APLA status of the patients by critical review of objective tests that had been performed at the time of symptomatic presentation and by performing venous Doppler ultrasound of the legs to elicit venous reflux as an indication of previous venous thrombosis. The presence of APLA was determined by coagulation assays for the lupus anticoagulant (LA) using five tests with well-defined control ranges and by ELISA assay for anticardiolipin antibodies (ACLA). These tests were measured on two separate occasions. The results of the study demonstrate a statistically significant association between persistently abnormal ACLA assays and thromboembolic events and a non-significant trend between persistently abnormal LA and thromboembolic events. Transient abnormalities of LA and ACLA were less strongly associated with thromboembolic events. We conclude that in patients with SLE, there is a significant association between thromboembolism and APLA.

Autoantibodies↗
PubMed1991

Heparin sensitivity and resistance in the neonate: an explanation.

Based on in vitro tests, newborns are reported to be both sensitive and resistant to standard heparin (SH) compared to adults. The sensitivity to SH occurs in assays based on de novo thrombin generation, and SH resistance occurs in systems where exogenous thrombin is added to newborn plasma. We hypothesized that this apparent paradox is related to the antithrombin III to (pro) thrombin ratio associated with each test. Since SH catalyses the activity of antithrombin III, any imbalance in the antithrombin III/(pro)thrombin ratio in newborns compared to adults would be amplified by SH. If the ratio of antithrombin III/(pro)thrombin is defined as 1 in adults, in comparison newborns have a ratio of 1.5. We compared how various doses of SH (0.1 to 0.6 u/ml) inhibited the generation of endogenous thrombin in defibrinated newborn (N) and adult (A) plasma. Following contact activation and recalcification of each plasma, thrombin activity was measured using a chromogenic substrate and quantitated by measuring the area under the curve. In the presence of SH, newborn plasma was more sensitive to SH than adult plasma and generated relatively less thrombin (N:6.1 vs A:9.1% sec/u/ml; p less than 0.01). When the ratio of antithrombin III/(pro)thrombin in newborns was altered to 2.5 by exogenous antithrombin III, the SH sensitivity was increased. This plasma now generated no detectable thrombin in the presence of only 0.1 u/ml of SH. In contrast, when the ratio of antithrombin III/(pro) thrombin of the newborn was altered by exogenous prothrombin to 0.6, this plasma now became resistant to SH and generated more thrombin than adults in the presence of SH (N:11.6 vs A:9.1; p less than 0.01). Because of the potential use of low molecular weight heparins (LMWH) in newborns, a LMWH, Choay 222, was also tested in a similar fashion and gave similar results to SH. Thus, the ratio of antithrombin III/(pro)thrombin likely determines the in vitro sensitivity or resistance of newborn plasma to SH and LMWH. There are no clinical studies that determine if newborns require more or less SH than the adult to successfully treat thrombotic complications. Current practice is a simple extrapolation of therapeutic ranges from adults. We speculate that the efficacy and safety of SH in the newborn in vivo can be improved by altering the antithrombin III/(pro)thrombin ratio.

Adult↗
PubMed1991

Glutamate receptor antagonists block cocaine-induced convulsions and death.

The involvement of excitatory amino acid (EAA) receptors in mediation of the toxic effects of cocaine was studied in male ICR mice. Cocaine HCl (90 mg/kg, IP) induced seizures in 95% and death within 24 h in 68% (n = 135) of the animals. There was a significant correlation (r = .54) between the time to onset of convulsions and the time to death in mice which died within 30 min of injection (n = 84). Pretreatment with selected EAA receptor antagonists 15 min prior to cocaine differentially blocked cocaine toxicity. Selective N-methyl-D-aspartic acid (NMDA) receptor antagonists (MK-801, dextrorphan, CPP) decreased both the incidence of seizures and mortality. A nonselective EAA antagonist, kynurenic acid, decreased lethality in doses which did not reduce convulsions. A similar action was observed following pretreatment with the selective kainic acid/AMPA receptor antagonist, GDEE. Antagonists at EAA receptors can provide significant protection against cocaine-induced toxicity. Moreover, the data provide evidence for the involvement of both NMDA and non-NMDA receptor subtypes in aspects of cocaine toxicity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Maintenance of the patency of indwelling central venous catheters: is heparin necessary?

The use of indwelling central venous catheters for the ambulatory management of children with cancer has been well described. There remains uncertainty as to the best method for maintaining the patency of these catheters. The standard approach at our institution is to flush the catheter twice daily with a solution containing heparin. This is both costly and inconvenient for most families. We describe a randomized cross-over study designed to compare the standard approach to a less intense program using an isotonic saline flush once a week. Evaluation continued for approximately 1,515 days in each study arm. The catheters were monitored for blockage, clot formation, and infection. One catheter blocked in a patient receiving the experimental method of care. Two episodes of thrombus formation were demonstrated at the end of the study (one in each of the study arms). The incidence of infection, while in keeping with our overall experience, was higher in the experimental arm. This led to a subsequent study, reported separately in this symposium. The results indicate that there is no significant difference, in the incidence of blocked catheters or other complications, between the two forms of care.

Adolescent↗
PubMed1991

Evaluation of a home intravenous antibiotic program in pediatric oncology.

We conducted a pilot program of home intravenous antibiotic therapy for the management of febrile neutropenic episodes in a population of children with cancer. During a 6-month period, 13 children/families participated in the successful treatment of 22 episodes of infection. A cost analysis of the program indicates that home therapy is considerably cheaper than in-hospital treatment. Although the program represents an incremental cost to the hospital, it does provide for more efficient health care delivery. Feedback from parents who participated was highly favorable. We believe that home intravenous antibiotic therapy is a safe and efficacious alternative to hospital management of children with malignant diseases admitted with fever and neutropenia.

Anti-Bacterial Agents↗
PubMed1991

Cardiopulmonary function during long-term central venous catheterization.

A prospective study was performed in an ambulatory group of infants, children, and young adults with neoplastic disorders to determine the prevalence of significant cardiopulmonary complications during long-term central venous catheterization. A cohort of 20 consecutive patients who had central venous catheters in situ for a mean of 13.5 months underwent pulmonary function testing, chest radiography, ventilation perfusion lung scintigraphy, electrocardiography, and echocardiography. No significant complications were seen. Specifically, there was no evidence of localized thrombus formation or pulmonary emboli, and no indirect evidence of pulmonary hypertension. In addition, we reviewed retrospectively the autopsy reports of 15 patients who died with central venous catheters in place. Three of these patients had superficial endocardial reactions. One patient had a right atrial mural thrombus related to the catheter, but two other patients were noted to have left atrial mural thrombi. This study demonstrates that central venous catheters can be used safely on a long-term basis in ambulatory patients requiring frequent venous access for treatment of their neoplastic disorders.

Adolescent↗
PubMed1991

Influence of fetal pulmonary epithelium on thrombin activity.

Epithelial injury and intra-alveolar fibrin are present in lung injury. To determine whether healthy fetal and neonatal lung epithelium could regulate thrombin activity (hence fibrin formation) we collected amniotic and postnatal endotracheal tube fluids from humans and directly sampled lung and amniotic fluids from fetal guinea piglets, rabbit pups, and lambs. The coagulant properties of the cell surface and media conditioned by rat fetal type II alveolar epithelium were assessed. All fluids contained glycosaminoglycans (GAGs), but mass and biological assays demonstrated only some (heparan sulfate and to a lesser extent dermatan sulfate) had antithrombin activity. The presence of proteoglycans (greater than 1,000 kDa) yielding active GAGs with less than 100 kDa after base elimination were demonstrated by Sepharose CL4B chromatography. Epithelial-derived fluids contained a factor VII-dependent procoagulant activity, but concentrated conditioned media overlying primary cultures of type II epithelium demonstrated a net antithrombin effect. These studies demonstrate that the lungs of human and nonprimate mammalian fetuses and fetal type II epithelium secrete GAGs, some of which possess antithrombin activity, which would oppose intra-alveolar fibrin formation.

Amniotic Fluid↗
PubMed1991

A549 lung epithelial cells synthesize anticoagulant molecules on the cell surface and matrix and in conditioned media.

To investigate mechanisms regulating intra-alveolar coagulation, we studied monolayers of the A549 human lung epithelial cell line. The surface of A549 cells delayed the onset of prothrombin-to-thrombin conversion and prevented total prothrombin consumption in normal plasma compared to plastic cell-free wells. Similar results were achieved with bovine pulmonary endothelial (CPAE) and rat intestinal epithelial (IEC-6) cell lines, whereas Madin-Darby canine kidney renal epithelial cell line accelerated thrombin formation. The A549 surface catalyzed antithrombin III-thrombin complex formation with no significant increase in thrombin inactivation from heparin cofactor II. The A549 cell surface effects were largely, but not completely, reversed to values obtained for plastic when protein C-deficient plasma was used. Pretreatment of the cell surface with chondroitinase ABC plus heparitinase prior to thrombin generation experiments had no effect on the total prothrombin consumed but decreased the initial delay. Heparan sulfate as well as dermatan sulfate and other chondroitin sulfates were detected on the A549 surface using alcian blue staining. Conditioned media from A549, CPAE, and IEC-6 cells delayed the clot time of recalcified plasma. Use of chondroitinase ABC and heparitinase were both required to obliterate the A549 conditioned media activity. After growing A549 cells in 35SO(2-)4-containing medium, the resultant conditioned medium was found to contain 2,000 kD and 300- to 1,000-kD proteoglycans that yielded chains of less than or equal to 100 kD on reductive elimination with base.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Tax incentive for Australian research and development.

The commercial rewards which can flow from the successful exploitation of R & D should encourage investment in biotechnological activities. Furthermore, the dynamic nature of biotechnology world-wide requires companies in the industry to constantly strive for significant advances which will provide them with a competitive advantage. In endeavouring to achieve such benefits, a significant cost saving may be available for a project which qualifies for the R & D tax concession. Accordingly, close consideration should be given to its availability and the conditions relevant to its eligibility.

Australia↗
PubMed1991

[Drug prescribing for 0-12-year-old children in Norway].

The first part of a project initiated at the Department of Pharmacotherapeutics, University of Oslo, on use of drugs in the treatment of children involved a study of prescriptions in September 1986. All pharmacies in the country were asked to record all drugs prescribed to 0-12 year old children during one week. 87 per cent of all Norwegian pharmacies took part in the study and data were recorded for 7587 prescribed drugs. Drug prescribing was highest in the county of Hedmark, and lowest in the county of Troms. For the age group 0-10 years 23 per cent more drugs were prescribed to boys than to girls. Infants (0-1 year) were prescribed drugs ten times more often than the oldest children. 3 per cent of the infants (0-1 year) were prescribed drugs during the week the study took place. More than 43 per cent of the total prescriptions were for drugs for the respiratory organs. Anti-asthmatics comprised the largest subgroup (796 prescribed drugs). Boys were prescribed 65 per cent more anti-asthmatics than girls. Every 20th of the total prescriptions was for an oral decongestant. There are few rational reasons for prescribing drugs in this group. As a single group, systemic antibiotics were the drugs most often prescribed, and accounted for as much as 30 per cent of the total prescriptions. The observed choice of antibiotics does not seem to agree with Norwegian recommendations.

Age Factors↗
PubMed1990

[Prescription of drugs in Norway to children aged 0-12 years].

The first part of a project initiated at the Department of Pharmacotherapeutics, University of Oslo, on use of drugs in the treatment of children involved a study of prescriptions in September 1986. All pharmacies in the country were asked to record all drugs prescribed to 0-12 year old children during one week. 87% of all Norwegian pharmacies took part in the study and data were recorded for 7,587 prescribed drugs. Drug prescribing was highest in the county of Hedmark, and lowest in the county of Troms. For the age group 0-10 years 23% more drugs were prescribed to boys than to girls. Infants (0-1 year) were prescribed drugs ten times more often than the oldest children. 3% of the infants (0-1 year) were prescribed drugs during the week the study took place. More than 43% of the total prescriptions were for drugs for the respiratory organs. Antasthmatics comprised the largest subgroup (796 prescribed drugs). Boys were prescribed 65% more antasthmatics than girls. Every 20th of the total prescriptions was for an oral decongestant. There are few rational reasons for prescribing drugs in this group. As a single group, systemic antibiotics were the drugs most often prescribed, and accounted for as much as 30% of the total prescriptions. The observed choice of antibiotics does not seem to agree with Norwegian recommendations.

Anti-Bacterial Agents↗
PubMed1990

[Treatment of infections caused by group A beta-hemolytic streptococci].

Since 1987 the number of severe and fatal cases of group A-beta-hemolytic streptococci (GAS) infections has increased in Scandinavia. It therefore seems reasonable to stress the monitoring, diagnosis and treatment of infections caused by GAS. Treatment with phenoxymethylpenicillin for ten days is recommended for patients with uncomplicated disease. Patients with severe disease should be treated with benzylpenicillin intravenously. We discuss alternative antibiotics, treatment of immunological complications, and general hygienic precautions.

Adult↗
PubMed1990

[The challenges of differential diagnosis of infections caused by beta-hemolytic streptococci].

Infections due to Streptococcus pyogenes are varied and often difficult to diagnose. During the last few years the clinical manifestations of these infections and the treatment rationale have changed. New diagnostic tests have been introduced. The present article reviews the diagnostic possibilities based upon clinical findings, the doctor's own laboratory and the microbiological laboratory. Rapid immunological tests, differential leukocyte count and C-reactive protein are pointed out as potentially useful laboratory tools for the clinician.

C-Reactive Protein↗
PubMed1990

Thrombin generation in newborn plasma is critically dependent on the concentration of prothrombin.

The ability to generate thrombin is decreased and delayed in plasma from the healthy newborn infant compared to the adult. Only 30 to 50% of peak adult thrombin activity can be produced in neonatal plasma. To test whether this observation can be explained by the low neonatal levels of the contact or vitamin K dependent factors, we measured neonatal thrombin generation after raising the concentration of these factors to adult values. We also determined whether the addition of a variety of blood products to neonatal plasma improved thrombin generation. An amidolytic method was used to quantitate intrinsic (APTT) and extrinsic (PT) pathway thrombin generation in defibrinated pooled cord plasma from healthy term infants. Added individually, factors VII, IX, X or the contact factors (CF) failed to alter the rate or the total amount of thrombin generated in neonatal plasma. In contrast, the addition of prothrombin increased the total amount of thrombin generated to above adult values in both the APTT and the PT systems but did not alter the rate of thrombin generation. The rate of thrombin generation in cord plasma shortened after a combination of II, IX, X and CF was added to the APTT system or II, VII and X to the PT system. In both systems, the total amount of thrombin generated was linearly related to the initial prothrombin concentration. Each of fresh frozen plasma, cryoprecipitate, plasma from platelet concentrates, or factor IX concentrate (in amounts used therapeutically) caused an increase in the total amount of thrombin generated which was related to the increase in prothrombin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Factors↗
PubMed1990

Evaluation of an automated bleeding time device in the newborn.

Sick infants frequently developed impaired hemostasis as a secondary event. Abnormal platelet-vessel wall interaction contributes to the hemorrhagic side effects. Currently, the bleeding time is the best measure of in vivo platelet participation in small vessel hemostasis. Bleeding times in the newborn have been previously determined with an automated device designed for the adult or with nonautomated devices. The automated bleeding time device for the adult is not suitable for the infant (length 5 mm, depth 1 mm). We evaluated the performance of an automated bleeding time device designed specifically for the newborn making a cut 2.5 mm in length and 0.5 mm in depth. The results with the automated device showed a strong correlation with the modified template bleeding time device previously used for the newborn. The normal range was shorter and the sensitivity to abnormal vessel wall interaction was greater with the automated device. As well, the ease of determining the bleeding time with the automated device was considerably improved over the template device.

Bleeding Time↗