Search PubMed⌕ Search

Biomedical subjects

M Andrew

Publications and source records attributed to M Andrew.

At least 91 records · Page 5Linked to original sources

The application of EMLA and glyceryl trinitrate ointment prior to venepuncture.

The efficacy of EMLA cream combined with glyceryl trinitrate (GTN) ointment was assessed by a double-blind prospective study. Adult female patients were randomly allocated to receive either EMLA 1 ml or 2 ml combined with GTN 2 mg, or EMLA 2 ml only. The difference in pain scores between the three groups was not statistically significant. When GTN was used with EMLA, the quality of the veins was superior and aided intravenous cannulation. There were no significant side-effects. It is concluded that if GTN is used with EMLA, the dose of EMLA can be reduced and intravenous cannulation is technically easier compared with EMLA alone.

Adult↗

Decreased thrombin activity of fibrin clots prepared in cord plasma compared with adult plasma.

We hypothesized that the immaturity of the newborn coagulation system may influence the procoagulant activity of clotbound thrombin. 125I-Labeled fibrin clots were prepared from adult and cord plasma, incubated in their respective plasmas, and fibrinopeptide A (FPA) production was measured. Cord plasma clots generated significantly less FPA compared with adult plasma clots (p < 0.001). Cord plasma clots incubated in adult plasma generated similar amounts of FPA as cord plasma clots in cord plasma. Adult plasma clots incubated in cord plasma clots generated more FPA than adult plasma clots in adult plasma. Adult and cord plasma clots were then incubated with purified human adult fibrinogen, and the discrepancy between adult and newborn plasma clots remained (p < 0.01). To compare the amount of clot bound thrombin, adult and cord plasma clots were sonicated and incubated with fibrinogen. Again, significantly less thrombin was seen in cord clots compared with adult clots (p < 0.01). Because cord plasma has lower prothrombin concentrations (0.5 U/mL) we increased cord plasma prothrombin concentration by the addition of purified prothrombin. Prothrombin supplemented cord plasma clots generated more thrombin than unsupplemented clots (p < 0.01) and in amounts similar to the adult system. In conclusion, decreased amounts of thrombin present in cord plasma clots compared with adult plasma clots results in less FPA production. The low plasma concentration of prothrombin in cord plasma is responsible for this phenomenon.

Adult↗

[Guidelines for understanding and treating chronic obstructive lung diseases. Institute for Pharmacotherapy].

A group of chest physicians, general practitioners, clinical pharmacologist and pharmacists appointed by the Institute of Pharmacotherapy, University of Oslo has evaluated the present knowledge about treatment of chronic obstructive lung disease. The group discusses today's medical treatment of this rather numerous group of patients. It is stated that, to a high degree, the treatment of these patients lacks proper documentation, and that treatment needs to be tested out on an individual basis. The group proposes a flow chart for this purpose.

Humans↗

INR reporting in Canadian medical laboratories. Thrombosis Interest Group of Canada.

A written survey of all licensed medical laboratories in Canada performing coagulation testing was performed to investigate the level of knowledge and overall usage of the INR system for reporting prothrombin time results in medical laboratories. There was an overall response rate of 857 of 1,228 laboratories surveyed. Fifty-seven percent of responding laboratories utilized some format of INR reporting. The ISI of the individual thromboplastin utilized was known by 89% of laboratories. The ISI of the thromboplastin utilized was known to be specific for the particular reagent/instrument combination in 44% of cases. Fifty-five percent of client physicians preferred PT results to be reported in seconds while 42% desired an INR format. The situation in Canada is similar to the United States in that further education regarding the INR system for PT reporting is required by both medical laboratories and physicians.

Administration, Oral↗

Antigen specificity of the ovine cytotoxic T lymphocyte response to bluetongue virus.

Bluetongue virus (BTV), an arbovirus transmitted by midges, can cause serious disease in sheep. Both virus neutralizing antibody and cytotoxic T lymphocytes (CTL) have been shown to have a role in protective immunity. In this study, the antigen specificity of CTL from BTV-immune sheep has been determined using recombinant vaccinia viruses expressing individual BTV antigens. The results show that, in the sheep studied thus far, the serotype-specific outer coat protein, VP2, and the non-structural protein, NS1 are major immunogens for CTL, with VP5 (an outer coat protein) and NS3 being minor immunogens. No VP7 (a major group-reactive inner coat protein) specific CTL were detected. The CTL from sheep immunized with serotype 1 were cross-reactive and able to recognize target cells infected with other BTV serotypes. Further work demonstrated that the cross-reactive CTL recognized NS1, but not VP2.

Animals↗

Home monitoring of warfarin therapy in children with a whole blood prothrombin time monitor.

We prospectively evaluated a capillary whole blood prothrombin time (PT) monitor (Biotrack, Ciba Corning) in an outpatient pediatric anticoagulation clinic (40 clinic patients) and in age-matched healthy subjects (30 control subjects). Subsequently, 23 children requiring warfarin therapy were placed on a home program (home patients) using the PT monitor; their parents were trained and the results followed by clinic staff. The PT results were reported as internationalized normalized ratios (INRs). The laboratory and PT-monitor INR values were similar for the clinic patients and the control subjects (y = 0.76x + 0.38; r = 0.93; p < 0.001). The accuracy of the PT monitor (the difference between INR values and the laboratory INR) was best at an INR of 2.5 to 3.5; 90% of paired INR values were within 0.8 INR units. The average duration of monitoring for home patients was 13 months (range, 2 to 60 months). They had an average of 3 dose measurements (range, 1 to 11 measurements) and 1.8 dose changes (range, 0.6 to 4.5 changes) per month. Of the 599 measurements, 63% were within the therapeutic range, similar to those for clinic patients; the dose requirements were also similar. There was 1 significant bleeding event, a subdural hematoma in a patient with an INR of 4.1, and 1 catheter-related thrombotic event with an INR of 1.2; both children recovered. Of the 23 families, one discontinued home monitoring because of parental discomfort, 2 children died of their primary disease, 6 completed warfarin therapy, and 14 remain on the home program. We conclude that the whole blood PT/INR monitor is safe and offers practical advantages to children requiring anticoagulation.

Adolescent↗

Cerebral vein thrombosis in childhood systemic lupus erythematosus.

We describe three cases of cerebral vein thrombosis (CVT) in girls with systemic lupus erythematosus. Severe, persistent, unremitting headache was a common manifestation. In the first patient, although the clinical features were suggestive of CVT, the diagnosis was delayed and she had a significant cerebral infarct. In the other two patients the diagnosis was made earlier and led to more rapid treatment; the institution of early therapy may have prevented further sequelae. The CVT was diagnosed in all patients with a combination of computed tomography and magnetic resonance imaging studies without the need for angiography. All patients were treated for their underlying systemic lupus erythematosus and with anticoagulation. All are receiving long-term low doses of warfarin and have not had any recurrences.

Adolescent↗

A cross-sectional study of catheter-related thrombosis in children receiving total parenteral nutrition at home.

We performed a cross-sectional evaluation of deep vein thrombosis (DVT) related to the use of central venous lines (CVLs) in all pediatric patients receiving home total parenteral nutrition at our institution (N = 12). All children (5 months to 17 years of age) were examined with bilateral upper limb venography. All CVLs were flushed daily with heparin (200 units). At the time of evaluation, 49 CVLs had been placed in the 12 children. Of the 39 CVLs removed, 27 (66%) were blocked; venograms had not been previously obtained except of one child. Eight children had clinical evidence of superficial collateral circulation in the upper portion of the chest and the upper extremities; five had intermittent symptoms of superior vena cava obstruction. On venography, 8 of the 12 children had extensive evidence of DVT; two were unilateral and six bilateral. Five children were treated with warfarin (0.12 to 0.28 mg/kg per day) to achieve an international normalized ratio of 1.4 to 1.8. Neither bleeding nor further CVL-related DVT has occurred. We conclude that the risk of CVL-related DVT in children requiring home total parenteral nutrition is high, and that venography should be performed early in the event of CVL blockage. A multicenter, controlled trial assessing optimal warfarin therapy in this patient population is indicated.

Adolescent↗

Developmental hemostasis: relevance to hemostatic problems during childhood.

Congenital and acquired hemostatic disorders present during childhood. An accurate diagnosis is critically important in order to implement optimal therapy. Over the last century, several investigators have measured plasma concentrations of hemostatic components in newborns and compared the results to adult values. Clinically significant differences exist for many hemostatic components. Recently, three large studies in more than 400 healthy children have provided reference ranges for hemostatic components throughout childhood. Together, these studies provide insight into the regulation of coagulation and fibrinolysis in children in physiologic and pathologic states. Some examples of the influence of age on hemostasis are: (1) the diagnosis of some congenital factor deficiencies, based on plasma levels, can be difficult due to physiologically low values; (2) despite very low levels of many inhibitors of hemostasis, thrombotic complications are rare; (3) the interaction of anti-coagulants and thrombolytic agents is profoundly influenced by the relative immaturity of hemostasis at birth; and (4) in contrast to the risk of thrombosis, healthy infants are at risk for vitamin K deficiency bleeding due to poor transport of vitamin K across the placenta and plasma concentrations of the vitamin K dependent proteins of less than 50% of adults values. The following review discusses the age dependency of hemostasis during childhood and the effect of the physiologically immature system on the diagnosis and treatment of hemostatic disorders.

Age Factors↗

Hemostasis in childhood acute lymphoblastic leukemia: coagulopathy induced by disease and treatment.

Thromboembolic events (TE) are serious complications of treatment for childhood acute lymphoblastic leukemia (ALL) that result in significant morbidity and occasionally mortality. These events are strongly associated with the administration of L'asparaginase (ASP). There have been many studies reporting TE and assessing the coagulopathy associated with treatment. The intention of these studies was to determine a potential mechanism for thrombosis. This article reviews the current literature in this area. First, data on thrombotic complications in terms of incidence, location, diagnosis, and timing of events are summarized. The second section discusses the coagulopathy associated with the disease and treatment. To minimize the effects of confounding treatments, the data are divided into sections covering pretreatment, after ASP only, after combination chemotherapy without ASP, and after combination chemotherapy with ASP. In addition, the effects of glucocorticoid steroids on the hemostatic system are discussed. As thrombin regulation is critically important to hemostasis, the next section of the review discusses the regulation of thrombin in children with ALL, both in vitro and in vivo, and the link between impaired thrombin regulation and TE in this population. Finally current hypothesis on mechanisms for TE and proposed preventative strategies are examined.

Anticoagulants↗

Cognitive function, thyroid status and postpartum depression.

Impairment of cognitive function can occur with thyroid disorder and also with depression. Since depression occurs in conjunction with postpartum autoimmune thyroiditis, the question arises as to whether any impairment of cognitive function in postpartum women is related to change in thyroid status or to depressed mood. A total of 242 women (110 thyroid antibody-positive and 132 antibody-negative) were assessed at 8, 12, 20 and 28 weeks postpartum in the outpatients of a district general hospital. Thyroid antibody levels (antimicrosomal and antithyroglobulin) were monitored at monthly intervals, together with plasma T3, T4 and thyroid-stimulating hormone. The main outcome measures were Research Diagnostic Criteria for depression, the 17-item Hamilton Depression Rating Scale and the Edinburgh Postnatal Depression Scale, together with reaction time and digit span. Subjects with postnatal depression showed detectable cognitive impairment independent of thyroid antibody status and actual thyroid dysfunction.

Antibodies↗

alpha 2-Macroglobulin remains as important as antithrombin III for thrombin regulation in cord plasma in the presence of endothelial cell surfaces.

Infants and children rarely develop thrombotic complications compared with adults, suggesting that there are protective mechanisms in place for the young. Because endothelial cell surfaces regulate thrombin formation and inhibition, we compared thrombin regulation by human umbilical vein endothelial cell surfaces exposed to defibrinated cord and adult plasmas. After activation by either 10% activated partial thromboplastin reagent (strong activator) or coagulant phospholipids (weak activator) the following were measured: free thrombin, thrombin bound to antithrombin III (ATIII), heparin cofactor II, alpha 2-macroglobulin (alpha 2M), and prothrombin concentration. Free thrombin activity was expressed as remaining activity, after subtraction of thrombin-alpha 2M activity. After 10% activated partial thromboplastin reagent, 100% of prothrombin was consumed and significant amounts of thrombin generated by 2 min. Cord plasma generated significantly less thrombin than adult plasma, reflecting the lower initial plasma concentration of prothrombin. correspondingly, concentrations of thrombin inhibitor complexes were significantly greater in adult plasma than in cord plasma. After coagulant phospholipids, 50% of prothrombin was consumed and negligible thrombin activity measured for both adult and cord plasma. Similar amounts of thrombin inhibitor complexes were formed. ATIII was the predominant inhibitor of thrombin in adult plasma, whereas alpha 2M was as important as ATIII in cord plasma for both activators. When cord plasma concentrations of ATIII were increased to adult values, the proportion complexed to alpha 2M decreased. We conclude that on human umbilical vein endothelial cells, the capacity to generate thrombin is decreased in adult and cord plasmas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neonatal thrombosis: report of a prospective Canadian and international registry.

OBJECTIVE: We sought to obtain representative data on the risk factors, diagnosis, current management, and short-term outcome of neonatal thrombosis. RESEARCH DESIGN: A case registry was established at McMaster University. Standardized questionnaires were mailed to collaborators at participating centers every 4 to 6 months. SETTING: Eighty-five level III and modified level II neonatal units in North America, Europe, and Australia were invited to join the registry. PATIENTS: Eligible infants were born between January 1990 and June 1993. Large-vessel thrombosis was diagnosed during the first month of life or up to 44 weeks post-conception after premature birth. The clinical impression of thrombotic vessel obstruction was confirmed using at least one imaging technique. RESULTS: Physicians in 64 centers expressed their willingness to participate. A total of 97 cases (excluding stroke) were registered from 29 centers. Spontaneous renal venous thrombosis (n = 21) was diagnosed at a median age of 2 days. The other venous (n = 39), arterial (n = 33), and mixed (n = 4) thromboses presented later; 89% of them were associated with an intravascular catheter and 29% with systemic infection. Doppler ultrasonography was the definitive diagnostic test in 68% of cases; contrast angiography was performed infrequently (14%). A third of all patients (but 62% of infants with renal venous thrombosis) received supportive therapy only. Thrombolytic agents were prescribed for 28% of catheter-associated venous thromboses and 30% of all arterial thromboses. The remainder of the patients were given heparin. Most patients (82%) survived to hospital discharge. Mortality rates were highest among infants with aortic thrombosis or central venous line-associated thrombosis affecting the right atrium or the superior vena cava (33%). CONCLUSIONS: Neonatal thrombosis is diagnosed fairly rarely. With the exception of spontaneous renal venous thrombosis, almost all cases are associated with indwelling catheters. Doppler ultrasound techniques are the most popular means of confirming the diagnosis in virtually all centers. Treatment varies greatly among different centers, probably because of the lack of scientific evidence about the optimum management of affected infants.

Canada↗

Inhibition of thrombin by antithrombin III and heparin cofactor II in vivo.

The critical role of thrombin in the pathogenesis of venous and arterial thrombosis, and the effectiveness of glycosaminoglycans as antithrombotic drugs are well known. Antithrombin III is a major inhibitor of thrombin and augmentation of its inhibitory actions by heparin is the basis for the clinical uses of heparin. Recent clinical and experimental studies have demonstrated that another glycosaminoglycan, dermatan sulfate, is an effective antithrombotic drug. Dermatan sulfate catalyses the inhibition of thrombin by heparin cofactor II. The concentrations of heparin cofactor II are higher in the plasmas of individuals with congenital antithrombin III deficiency and pregnant women than controls. The role of heparin cofactor II as a physiologic thrombin inhibitor is unknown. Enzyme-linked immunosorbent assays were used to quantify thrombin-heparin cofactor II and thrombin-antithrombin III endogenous to the plasmas of adult antithrombin III-Hamilton deficient subjects, their siblings with normal antithrombin III levels, pregnant women at term and 3 to 5 days after delivery. Both thrombin-antithrombin III and thrombin-heparin cofactor II complexed with vitronectin were detected in all the plasmas. Significantly, the concentrations of thrombin-heparin cofactor II-vitronectin were higher in the plasmas of congenital antithrombin III deficient subjects and in pre- and post-delivery plasmas than those of normal subjects. In addition, the concentrations of thrombin-heparin cofactor II decreased 3 to 5 days after delivery, reflecting the disappearance of the catalytically active dermatan sulfate elaborated by the placenta. Thus, heparin cofactor II normally inactivates thrombin in vivo, with its role increasing in conditions associated with high levels of heparin cofactor II and/or dermatan sulfate.

Adult↗

Changes in diurnal blood pressure variation and red cell and plasma volumes in patients with renal failure who develop erythropoietin-induced hypertension.

Hypertension is the most common side-effect of treatment with recombinant human erythropoietin (EPO) for the anemia of chronic renal failure. To elucidate why this occurs in some patients we measured changes in blood volumes and diurnal blood pressure (BP) variation during treatment. Isotope labelled measurements of red cell and plasma volume (RCV and PV) were carried out along with ambulatory BP monitoring before starting EPO and after target hemoglobin (Hb) was reached. RCV did not differ between the patient group developing EPO-induced hypertension (EpHT, n = 11) and the group with no change in BP (NC, n = 13) either before or after treatment. However PV was significantly lower in the EpHT group after treatment (2.97 vs 3.92 litres; p < 0.025). Mean BPs differed little between groups because antihypertensive medications were increased as necessary for clinical safety but after achieving target Hb, day-night difference in diastolic BP was greater in the EpHT than the NC group (11.5 vs 4.6 mmHg; p < 0.025) due to a greater rise in daytime BP. There were significant correlations between high day-night diastolic BP differences after EPO in all the studied patients and low plasma volumes either pre- or post-EPO. The study group was heterogeneous but the changes were in the same direction irrespective of type of renal replacement therapy. These results suggest that EPO-induced hypertension is associated with increased daytime vasoconstriction and greater hemoconcentration due to lower plasma volume.

Anemia↗