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Biomedical subjects

M Andrew

Publications and source records attributed to M Andrew.

At least 145 records · Page 8Linked to original sources
PubMed1993

Primary immunization series for infants: comparison of two-component acellular and standard whole-cell pertussis vaccines combined with diphtheria-tetanus toxoids.

At 2 months of age, 145 infants were randomized to receive either a two-component acellular pertussis vaccine [lymphocytosis-promoting factor (LPF)/filamentous hemagglutinin (FHA)] or standard whole-cell pertussis vaccine, each combined with diphtheria-tetanus toxoids, as their primary immunization series. Of the 132 subjects (91%) who completed the study, those receiving the acellular vaccine had significantly fewer adverse reactions: 5% vs 30% (local) and 17% vs 30% (systemic, including fever). During the first 24 hours acetaminophen usage, a general measure of adverse reactions, was lower in the test group. Overall, 35% of the acellular vaccine doses were reaction free vs 12% of the whole-cell doses. No serious reactions occurred in either group. Antibody responses to LPF and to FHA were significantly increased after the second and third immunizations with the test vaccine and were consistently higher than levels achieved with the standard vaccine. Thus the two-component acellular pertussis vaccine was associated with fewer adverse reactions and improved serologic responses to LPF and FHA as compared with the currently recommended whole-cell vaccine.

Academic Medical Centers↗
PubMed1992

Maturation of the hemostatic system during childhood.

The hemostatic system is assumed to be similar in children and adults and reference ranges established for adults are commonly used to evaluate children suspected of having congenital or acquired hemostatic problems. However, we know that the hemostatic system is not fully mature by 6 months of age and comprehensive studies of healthy older children have not been published. Therefore, we conducted a prospective cohort study of the hemostatic system in healthy children having minor, elective day surgery. After obtaining informed consent, a 3-mL blood sample was obtained at the time routine preoperative blood work was drawn. The plasma was fractioned and stored at -70 degrees C for batch assaying. We measured the concentration of 33 components of the hemostatic system (functional and immunologic assays) and the bleeding time (automated pediatric device) in 246 children aged 1 to 16 inclusive (a minimum of four subjects at each age). Eleven components of hemostasis (fibrinogen, prekallikrein, high-molecular weight kininogen, factors VIII and XIII, antithrombin III [ATIII], heparin cofactor II [HCII], alpha 1-antitrypsin [alpha 1AT], protein S, plasminogen, alpha 2-antiplasmin [alpha 2AP]) had mean values and ranges of normal that were similar to adults. Mean values of seven coagulants (II, V, VII, IX, X, XI, XII) were significantly lower than adult values and varied with age. Values for three inhibitors, alpha 2-macroglobulin (alpha 2M), protein C, and protein C1-inhibitor (C1-Inh) also differed from adults. Alpha 2M and C1-Inh inhibitor levels were elevated throughout childhood, whereas protein C levels were low, with a lower limit of normal of 0.40 U/mL until the age of 11. Finally, the upper limit of normal for the bleeding time was longer in children during the first 10 years of life, but decreased to adult values in the teenage years. In summary, there are important physiologic differences in the hemostatic system in children compared with adults. The decreased levels of several critical coagulants and increased levels of alpha 2M may contribute in part to the lower risk of thrombotic events in childhood. Age-matched controls should be used for evaluation of the hemostatic system in children with suspected congenital or acquired defects.

Adolescent↗
PubMed1992

Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration.

Although thrombolytic drugs have been extensively used in adults, there is sparse information on their effectiveness in newborns whose fibrinolytic system differs significantly from adults. The purpose of this study was to determine if low plasma levels of plasminogen in cord plasma limited the therapeutic effectiveness of thrombolytic agents. Urokinase (UK), streptokinase (SK) and tissue plasminogen activator (TPA) were compared for their ability to lyse washed 125I-labelled adult or cord fibrin clots suspended in cord or adult plasma. 125I-labelled fibrin clots were prepared by recalcifying cord or adult plasma spiked with labelled fibrinogen and then placed into cord or adult plasma which contained either saline or differing amounts of a specific thrombolytic agent. After a 60 min incubation, the remaining 125I-fibrin in clots released 125I-fibrin fragments, and concentrations of fibrinogen, alpha 2-antiplasmin, and plasminogen in the bathing plasma were measured and compared to starting values. Cord fibrin clots were more resistant than adult fibrin clots to all thrombolytic drugs tested (p less than 0.001). On average, the cord system retained 27% more 125I-fibrin in clots, and released 32% less 125I-fibrin fragments into plasma. Fibrinogenolysis was also decreased in cord plasmas compared to adult plasmas. The degree of fibrinolysis and fibrinogenolysis in cord plasma increased to adult values when plasminogen concentrations were increased in the bathing plasma. Thus, cord fibrin clots have an impaired response to thrombolytic agents secondary to low levels of plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study.

To determine whether an association exists between the presence of antiphospholipid antibodies and pregnancy loss, a cross-sectional study was performed. Consecutive women who were referred to three outpatient rheumatology clinics and who had systemic lupus erythematosus (SLE) and a history of one or more pregnancies were evaluated. Patients were interviewed to determine outcomes of all previous pregnancies. Blood was taken on two separate occasions at least 3 months apart to test for the presence of the lupus anticoagulant and anticardiolipin antibodies; on both occasions, five tests of the lupus anticoagulant, with well-defined normal ranges, and an enzyme-linked immunosorbent assay to measure IgG anticardiolipin antibodies were performed. Patients were considered to be positive for the lupus anticoagulant if one or more tests was abnormal on both occasions and positive for anticardiolipin antibodies if the test was abnormal on both occasions. Forty-two women were studied. Statistically significant associations were shown between lupus anticoagulant positivity and previous pregnancy loss (odds ratio [OR], 4.8; 95% confidence intervals [CI], 1.0 to 23.6; P = .05) and between anticardiolipin antibody positivity and previous pregnancy loss (OR, 20.0; 95% CI, 1.3 to 97.0; P = .01). All seven women with multiple episodes of pregnancy loss were lupus anticoagulant positive and four of these were also anticardiolipin antibody positive. If patients who are transiently positive for lupus anticoagulant and/or anticardiolipin antibodies are considered to be test positive, the associations with pregnancy loss are no longer statistically significant. Within the group of lupus anticoagulant-positive patients, we observed stronger associations between the presence of six or more positive tests and pregnancy loss than between the presence of two to five positive tests and pregnancy loss. No single test for the lupus anticoagulant provides a statistically significant association with pregnancy loss. The results of our study show that by performing multiple lupus anticoagulant tests and by repeating testing for lupus anticoagulant and anticardiolipin antibodies on more than one occasion, significant associations between the presence of antiphospholipid antibodies and previous pregnancy loss can be shown in patients with SLE.

Abortion, Spontaneous↗
PubMed1992

[Antibiotic prevention of bacterial endocarditis].

Bacterial endocarditis is a serious condition with high lethality. The authors review the etiology of the disease and conditions and procedures associated with increased risk, and give recommendations on choice and dosage of effective antibiotics. Most cases of endocarditis are caused by gram-positive cocci of the genera Streptococcus, Enterococcus or Staphylococcus. The number of cases caused by staphylococci has increased in recent decades. Risk of acquiring endocarditis is higher, for example, in patients with prosthetic cardiac valves and in patients with a previous history of endocarditis. Interventions associated with increased risk include various procedures in the mouth, throat and upper airways, since this is where the bacteria most often causing endocarditis are to be found. A single oral dose of amoxycillin is recommended for standard prophylaxis, and ampicillin in combination with an aminoglycoside for parenteral use. In cases of penicillin allergy, a single oral dose of clindamycin is recommended in patients at risk of bacteriemia from the respiratory tract, with trimetoprim as an alternative for genito-urinary and gastrointestinal procedures. Vancomycin or vancomycin plus aminoglycoside is recommended as a parenteral regimen in cases of penicillin allergy.

Anti-Bacterial Agents↗
PubMed1992

Failure of thrombolytic therapy in four children with extensive thromboses.

In three children with central vein thromboses and a fourth with a pulmonary artery thrombosis, thrombolytic therapy failed to produce ultrasonographic evidence of clot lysis. Low-dose streptokinase (50 to 250 U/kg per hour) was infused directly into the clot in three children, followed by streptokinase and urokinase in systemic doses (streptokinase, 1000 to 1750 U/kg per hour; urokinase, 4400 to 5000 U/kg per hour). A fourth child treated sequentially with systemic doses of streptokinase, urokinase, and recombinant tissue-type plasminogen activator developed a significant retroperitoneal and intrapleural hemorrhage after 19 hours of recombinant tissue-type plasminogen activator infusion at a dose of 0.7 mg/kg per hour. All of the children survived. The most likely reason for treatment failure was that the clots (estimated to be between 2 and 3 weeks of age) were organized and thus resistant to lysis. Early diagnosis and prompt thrombolysis of significant lesions may contribute to the successful management of pediatric thrombosis. However, controlled studies are clearly needed to establish guidelines for the optimal use of thrombolytic agents in children.

Child↗
PubMed1992

Comparison of acellular (B type) and whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines as the first booster immunization in 15- to 24-month-old children.

We compared an acellular (B type) pertussis-component diphtheria-tetanus-pertussis (DTP-Ac) vaccine containing equal amounts of filamentous hemagglutinin and lymphocytosis-promoting factor with a conventional whole-cell vaccine as the first booster immunization in 162 healthy children 15 to 24 months of age. Fewer local reactions (e.g., erythema, swelling, and tenderness at the injection site) were seen in DTP-Ac vaccine recipients during the first 48 hours of observation. This group also had fewer episodes of fever (> or = 38 degrees C) and other systemic reactions (e.g., irritability, drowsiness, and anorexia). Overall, 57% of the DTP-Ac vaccine recipients had no obvious adverse reactions, in contrast to 5% in the comparison group. At 4 to 8 weeks after vaccination, serum antibody responses to filamentous hemagglutinin and lymphocytosis-promoting factor were greater in recipients of the acellular vaccine as determined by an enzyme-linked immunosorbent assay. We conclude that this B-type acellular vaccine is both immunogenic and much less likely to cause an adverse reaction than a currently licensed whole-cell vaccine, and is suitable for routine booster immunizing doses to protect against pertussis.

Analysis of Variance↗
PubMed1992

A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D.

We evaluated the effects of the intravenous administration of anti-D, an immune globulin directed at the D antigen on erythrocytes that is purified from plasma from sensitized persons, on patients with idiopathic thrombocytopenic purpura. To determine the most effective dose, the duration of response, and the side effects of this therapy in children, we performed a multicenter cohort study of escalating doses of intravenously administered anti-D in children aged 1 to 18 years with chronic idiopathic thrombocytopenic purpura, defined as idiopathic thrombocytopenic purpura persisting for more than 6 months with a platelet count of less than 50 x 10(9) cells/L. Twenty-five Rh-positive children received increasing doses of anti-D as follows: day 1, 25 micrograms/kg; day 2, 25 micrograms/kg; day 7, 35 micrograms/kg; day 14, 45 micrograms/kg; and day 21, 55 micrograms/kg. Administration of anti-D was stopped after day 21 or when the platelet count rose to greater than 150 x 10(9) cells/L or the hemoglobin level was 100 gm/L. Platelet count was less than 50 x 10(9) cells/L in all children before treatment. A response was defined as an increase in the platelet count to more than 50 x 10(9)/L and a doubling of the pretreatment platelet count. Of 25 children, 23 (92%) had responses by day 7 of the initial treatment protocol. Eighteen children (72%) had platelet counts greater than 150 x 10(9) cells/L by day 7 after two doses of anti-D. Median duration of response was 5 weeks (range 1 to 24 weeks). Average drop in hemoglobin level was 13.7 gm/L; in one child (a nonresponder) hemoglobin value fell to less than 100 gm/L. No other untoward side effects were seen. Of the 23 children who responded, 21 were retreated with one dose of anti-D when platelet counts returned to baseline values of less than 50 x 10(9) cells/L; all but three of the children who underwent retreatment showed a response the second time. Sixteen children continued to receive intermittent anti-D therapy after completion of the study, and all continued to have excellent responses. We conclude that anti-D is a safe, effective, and relatively inexpensive therapy for childhood chronic idiopathic thrombocytopenic purpura.

Adolescent↗
PubMed1992

Thrombin regulation in mother and fetus during pregnancy.

Pregnancy is characterized by an increase in plasma concentration of several coagulants and with little or no change in plasma concentrations of inhibitors of thrombin or thrombin generation with the exception of a decrease in protein S. The net effect of these physiologic differences from nonpregnant adults is that, in vitro, thrombin generation is slightly increased in pregnancy plasma. Thrombin inhibition may be altered by the presence of circulating dermatan sulfate proteoglycan. Based on information on placental structure and function and ex vivo markers of thrombin generation, it is clear that there must be local generation of thrombin with fibrin deposition in the placenta. The roles of the alterations in the hemostatic system in regulating this increased thrombin activity remain to be elucidated. In addition, regulation of thrombin at the vessel wall of the placenta needs to be further explored, since it is likely important in preventing locally increased thrombin generation from producing systemic effects, that is, thrombosis. The fetal coagulation system is an immature, developing system, as is evident from low and gradually increasing plasma concentrations of both coagulants and inhibitors. Some of these low levels result from decreased gene expression in the immature liver. However, others (Factors II, VII and VIII) are related to other processes that remain to be determined. There is a progressive increase in the levels of these factors with increasing gestational age but most remain below adult values at term. As a result, thrombin generation and inhibition in vitro are decreased. Since bleeding and thrombotic complications are not a feature of normal fetal life, it is likely that the hemostatic system is balanced. In vivo data on thrombin generation and inhibition are lacking and the interaction of the physiologically different plasma of the fetus with the vessel wall is only now being explored.

Blood Coagulation Factors↗
PubMed1992

Management of children with acute lymphoblastic leukemia by the Dana-Farber Cancer Institute protocols. An update of the Ontario experience.

The primary purpose of this study was to determine the therapeutic efficacy of a protocol of treatment for acute lymphoblastic leukemia (ALL) in children. A prospective approach was adopted with an inception cohort of patients. Outcome measures were assessed on December 31, 1990. The study was conducted at two tertiary care centres (pediatric oncology programs) in Ontario, Canada. All children with ALL were eligible for study and consecutive recruitment took place between May 1984 and July 1987. They were classified at diagnosis into one of three categories for risk of relapse according to standardized criteria. Thirty-nine children were designated as having standard risk (SR), 31 as having high risk (HR), and 12 as having very high risk (VHR) disease. All patients are included in the analysis. Treatment was administered according to risk category-specific chemotherapy protocols, the details of which have been published. A distinguishing feature of these strategies is the intensive use of intramuscular L-asparaginase. Patients remained on these regimens for 2 years or until relapse or toxic death (events) ensued. Total and event-free survival data were determined by life-table analysis (Kaplan-Meier plots). With a minimum interval from diagnosis of 186 weeks and a median interval exceeding 5 years, the cumulative proportion of the entire cohort (C) surviving is 85% [95% confidence interval (CI), 77-93%]. For the respective risk groups, the corresponding proportions are SR 94% (95% CI, 87-100%), HR 74% (95% CI, 59-89%), and VHR 81% (95% CI, 59-100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Coagulation screening tests in high risk neonates: a prospective cohort study.

Forty seven infants in a prospective cohort of 170 high risk neonates without signs of overt bleeding had abnormal coagulation screening tests within 36 hours of birth. Early thrombocytopenia was a better predictor of prolonged prothrombin times and hypofibrinogenemia than very low birth weight, fetal growth retardation, or poor five minute Apgar scores.

Blood Coagulation Disorders↗
PubMed1992

An anticoagulant dermatan sulfate proteoglycan circulates in the pregnant woman and her fetus.

Investigation of the in vitro ability of plasma from pregnant women to inhibit exogenous thrombin (25 nM) demonstrated that heparin cofactor II inhibited more thrombin (3.0 +/- 0.7 nM, mean +/- SD) than plasma from women 3-5 d postpartum (1.9 +/- 0.5 nM) or plasma from nonpregnant adults (1.5 +/- 0.4 nM). Levels of heparin cofactor II were only slightly increased over normal in both pregnant and postpartum women and did not account for the observed increase in thrombin bound to heparin cofactor II. Assay of pregnancy plasma for dermatan sulfate anticoagulant activity demonstrated the presence of activity equivalent to 0.23 +/- 0.02 micrograms/ml of porcine mucosal dermatan sulfate. This activity could not be demonstrated in normal adult plasma or plasma from women on the contraceptive pill. The mass of dermatan sulfate in pregnancy and umbilical cord plasmas was increased over adult control plasma by 0.20 micrograms/ml (53%) and 0.29 micrograms/ml (76%), respectively. The glycosaminoglycan-containing fraction of plasma was isolated and an assay for anticoagulant dermatan sulfate confirmed its presence in both pregnancy and cord plasmas but minimal activity in adult plasma. Gel chromatography of isolated fractions from both pregnancy and cord plasmas revealed a polydisperse, active species with apparent Mr 150,000 D. Reductive elimination decreased the apparent Mr of the active species on gel chromatography to 31,000 D for cord and 21,000 D for pregnancy products. This confirmed the presence of an anticoagulant active dermatan sulfate proteoglycan circulating in the plasmas of pregnant women at term and fetuses at delivery.

Anticoagulants↗
PubMed1992

Thrombin inhibition is impaired in plasma of sick neonates.

The sick neonate may develop spontaneous or catheter-related thromboses, which must in part reflect poor regulation of the formation and activities of the coagulation enzyme, thrombin. We hypothesized that the balance between the generation and inhibition of thrombin may differ in sick neonates compared with healthy neonates. Fifty neonates with respiratory failure requiring mechanical ventilation and 40 healthy neonates were studied on d 1 of life. All neonates had normal coagulation screening tests and a platelet count greater than 150 x 10(9)/L. Plasma pools from neonates with similar gestational age (GA), birth weight, and health status were prepared. Eight plasma pools from 40 healthy neonates of GA 30-38 wk were compared with six plasma pools from 30 sick neonates of GA 30-38 wk. An additional four plasma pools prepared from 20 sick neonates of GA less than 30 wk were studied. Thrombin generation was measured by amidolysis of a chromogenic substrate, S2238, after defibrination, contact activation, and recalcification of the test plasmas. The contributions of antithrombin III, heparin cofactor II, and alpha 2-macroglobulin as inhibitors of 125I-thrombin were quantitated by SDS-PAGE followed by autoradiography and densitometry. Thrombin generation was similar for both healthy and sick neonates of GA 30-38 wk. However, the inhibition of thrombin was impaired in plasma from sick neonates of GA 30-38 wk compared with plasma from healthy neonates of GA 30-38 wk (4.37 +/- 0.22 versus 5.21 +/- 0.21 nmol; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗