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Biomedical subjects

M Andrew

Publications and source records attributed to M Andrew.

At least 181 records · Page 10Linked to original sources
PubMed1990

Coagulation abnormalities in chronic peritoneal dialysis.

To determine whether children treated with chronic peritoneal dialysis have a hypercoagulable state, various coagulation and fibrinolytic factor concentrations or activities were measured in 17 children undergoing chronic peritoneal dialysis. The patients had significantly increased activities of factors VII and VIII, and increased concentrations of von Willebrand factor (vWF), fibrinogen, factor XIIIA and factor XIIIS compared to reference values (P less than 0.001 in each case). The activated partial thromboplastin time was prolonged (P less than 0.001) and the thrombin clotting time was decreased (P less than 0.05) in these children. The prothrombin time and activities of factors XII, XI, IX, X, V and II were not significantly different from control values. Protein C concentrations were similar to normal, but antithrombin III concentrations were increased (P less than 0.05). Within the fibrinolytic pathway, decreased concentrations of plasminogen were found (P less than 0.001) and the concentrations of alpha-2-antiplasmin were increased (P less than 0.001). The plasma albumin concentration was below 33 g/l in 13 of the 17 children. The duration of treatment with peritoneal dialysis was directly correlated with vWF concentrations (P less than 0.001) and inversely correlated with factor VII concentrations (P less than 0.01). Of these patients 2 have since had clinical thrombotic episodes. The coagulation abnormalities found may have a role in the occurrence of thrombosis complicating renal transplantation.

Adolescent↗
PubMed1990

Vaccinia virus-mediated damage of murine ovaries and protection by virus-expressed interleukin-2.

Vaccinia virus was shown to replicate in the ovaries of normal inbred mice and cause sufficient damage to ovarian follicles to decrease fertility of the mice. The mouse-adapted strain, VV-WR, had a greater affinity for growth in ovaries than the vaccine strains, VV-Elstree, VV-NYBH or VV-Copenhagen. Virus reached the ovaries after intravenous or intraperitoneal inoculation, but not after subcutaneous inoculation in the foot pad. Interleukin-2 (IL-2), when expressed by a recombinant vaccinia virus was able to decrease the titre of virus in the ovaries and prevent infertility. Both non-specific (natural killer cells) and antigen-specific mechanisms were active within the ovaries and may play a role in the IL-2-mediated clearance of vaccinia virus.

Animals↗
PubMed1990

Development of the hemostatic system in the neonate and young infant.

Our understanding of the coagulation and fibrinolytic systems (the hemostatic system) in the adult has progressed rapidly in recent years. However, a more complete understanding of the physiology of the hemostatic system in the neonate has lagged behind that of the adult for many reasons. First, the hemostatic system in the newborn exists in a dynamic state and is rapidly evolving toward the adult system. This situation necessitates the generation of not one, but several, reference ranges (or ranges of normal values) in the postnatal period for the various tests and components of the hemostatic system. Also, microtechniques must be used to perform the required assays, both because of the small size of blood samples available and because of the difficulty of obtaining blood from infants. Recently, many of these problems have been resolved, which resulted in a better appreciation of the development of the hemostatic system in the infant. This article reviews our current understanding of the protein components of the coagulation and fibrinolytic systems in the neonate. Reference ranges for normal values of the various tests and components of the hemostatic system have been provided for the premature and full-term infant at birth and during the first 6 months of life.

Aging↗
PubMed1990

A new short infusion dosage regimen of recombinant tissue plasminogen activator in patients with venous thromboembolic disease.

Although recombinant tissue-type plasminogen activator (rt-PA) has the potential to induce thrombolysis without producing a generalized coagulopathy, the dosage regimens in present use induce a plasma fibrinolytic state and are associated with bleeding. Animal experiments have demonstrated that rt-PA produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is increased and bleeding is reduced when rt-PA is administered over a short time period. To determine whether a short course regimen of rt-PA has potential in man, we gave a bolus injection of rt-PA (0.6 mg/kg) concurrently with heparin to five patients with venous thromboembolism. Three patients with angiographically proven pulmonary embolism had marked improvement of the perfusion defects when lung scans were repeated 24 h after rt-PA administration. In one of two patients with thrombosis of the deep veins of the upper extremity the venographic defect resolved completely. In three of four patients there was a mild decrease in fibrinogen and a moderate decrease in alpha 2-antiplasmin levels. There was no excessive bleeding. These results suggest that a bolus injection regimen of rt-PA has considerable potential in the treatment of thromboembolic disease.

Axillary Vein↗
PubMed1990

Neonatal thrombocytopenia in the hypertensive disorders of pregnancy.

Infants of hypertensive mothers are at risk for a platelet count below 150 x 10(9)/L. To define this risk and assess maternal factors influencing the prevalence of neonatal thrombocytopenia, we collected cord blood samples from 520 infants of 607 consecutive hypertensive mothers with singleton pregnancies. The platelet count in cord blood from infants of hypertensive mothers was compared with that of a control normotensive population, and other comparisons were made among various maternal hypertensive groups. The rate of neonatal thrombocytopenia was 9.2% in hypertensive patients, compared with 2.2% in infants of normotensive mothers (P less than .00001). In the hypertensive group, preterm birth was the major risk factor for neonatal thrombocytopenia. Term infants of hypertensive mothers were no more likely to be thrombocytopenic than were control infants. Only two infants, both preterm, had cord platelet counts below 50 x 10(9)/L. Although obstetric interventions are not indicated, the rate of thrombocytopenia in preterm infants born to hypertensive women justifies neonatal scrutiny.

Female↗
PubMed1989

Alpha-2-macroglobulin is an important progressive inhibitor of thrombin in neonatal and infant plasma.

Antithrombin III (ATIII) is the main inhibitor of thrombin in adult plasma; alpha 2-macroglobulin (alpha 2M) and heparin cofactor II (HCII) are of lesser importance. The relative contributions of these inhibitors to the inactivation of thrombin may differ during the neonatal period and infancy, when plasma concentrations of alpha 2M are about twice as high as those of ATIII. We therefore compared the relative importance of these anti-proteases for the inhibition of 125I-thrombin in defibrinated pooled adult and neonatal plasma. Observations were also made in pooled plasma of 6 months old infants. 125I-thrombin-inhibitor complexes were quantitated after SDS-PAGE and autoradiography by scanning densitometry. Thrombin (2.5 NIH U/ml) was inhibited more slowly in neonatal than in adult plasma. However, both plasmas inhibited 88% of the added thrombin by 5 minutes. Alpha 2M inhibited consistently a larger fraction of thrombin in neonatal than in adult plasma. Consequently, the ratio of thrombin bound to ATIII over thrombin bound to alpha 2M was significantly lower in neonatal (less than 2.5) than in adult plasma (greater than 4.5; p less than 0.0001). In infant plasma, this ratio was less than 2.0. Upon addition of therapeutic amounts of heparin (0.4 U/ml), differences between the contributions of ATIII and alpha 2M to the inhibition of thrombin were no longer apparent, as over 90% of complexed thrombin was bound to ATIII in heparinized plasmas of all age groups. We conclude that alpha 2M is an important progressive inhibitor of thrombin in young infants. This finding may explain why healthy newborns rarely suffer from thrombosis, despite their low plasma ATIII levels.

Adult↗
PubMed1989

The comparison of the pharmacokinetics of a low molecular weight heparin in the newborn and adult pig.

Standard heparin (SH) is frequently used in the sick neonate to prevent catheter related thrombosis. SH can cause significant bleeding complications in the adult and its use in the neonate is linked to an increased incidence of intraventricular hemorrhage. Recently available low molecular weight heparins (LMWH) offer potential advantages over SH in the adult by exhibiting a longer half life and decreased bleeding side effects compared to SH. Whether LMWHs would offer similar therapeutic advantages to the sick neonate is unknown. Using the porcine model of neonatal hemostasis we measured the pharmacokinetics of a LMWH (Choay 222) in the pig (ATIII level: 100%), in the piglet (ATIII level:50% of adult) and in the piglet given exogenous ATIII. All pigs were bolused with 125I-LMWH (5, 25 or 100 anti-factor Xa units/kg) and blood samples collected for the measurement of 125I-radioactivity, and anti-factor Xa activity. The half life of LMWH, measured as either 125I-radioactivity or as anti-factor Xa activity, was not dose dependent and was similar in pigs and piglets; however, the volume of distribution was greater in the piglet resulting in an increased total clearance compared to the pig. As well, the supplementation of the piglet with exogenous ATIII did not influence the pharmacokinetics of LMWH. The half life of the LMWH in both pigs and piglets was approximately twice as long as previously reported values for SH in the same animal model. Thus the longer half life of LMWH in the piglet, and the similarity of the half life in piglets and pigs suggest that LMWH may have a therapeutic advantage in the newborn over SH.

Aging↗
PubMed1989

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

There is ample evidence of the value of intensive therapeutic strategies in the management of acute lymphoblastic leukemia (ALL), the commonest form of malignant disease in children. Such a program, devised at the Dana-Farber Cancer Institute (DFCI), Boston, and incorporating high-dose L-asparaginase, was adopted in 1984 by the Children's Hospital at Chedoke-McMaster, Hamilton, Ont., and the Children's Hospital of Western Ontario, London. We describe the experience of these institutions in the treatment of 82 children with ALL, 19 of whom were switched to the DFCI protocols while in continuing first remission with other treatment programs to complete a minimum of 2 years of maintenance therapy; the remaining 63 children, who had recently diagnosed disease, were consecutively enrolled in the DFCI protocols. Each child was assigned at diagnosis to a category of risk for relapse and treated accordingly. There were no remission induction failures or deaths due to induction therapy among the patients with newly diagnosed disease. There were no differences in total or event-free survival rates between the patients in Hamilton and those in London or between those whose protocols were switched and those who were treated from the beginning with the DFCI protocols. With a median follow-up interval of 144 weeks the total survival rate was 95% and the event-free survival rate 88%. For patients at standard risk of relapse the event-free survival rate was 100%, for those at high risk the rate was 82%, and for those at very high risk the rate was 67%. If infants (all of whom suffered a relapse) are excluded from the last category the rate was 89%. These results were achieved with moderate toxic effects (except for two deaths, one of which was due to a therapeutic misadventure) and suggest that the prospect for cure in children with ALL. may now approximate 80%, a degree of success that demands that consideration be given to reducing total therapy, at least for children with standard-risk disease. Further follow-up will determine whether these high event-free survival rates will stabilize and meet the criteria for cure.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Modified bleeding time in the infant.

The present authors developed a modified template bleeding time for use in the newborn infant. The sensitivity of the bleeding time to the presence of antibiotics, indomethacin, generalized illness, and thrombocytopenia was tested in 242 infants. Both indomethacin and thrombocytopenia similarly prolonged the BT, and the latter could be corrected by raising the platelet count.

Anti-Bacterial Agents↗
PubMed1989

Neonatal autoimmune thrombocytopenia: role of high-dose intravenous immunoglobulin G therapy.

High-dose intravenous immunoglobulin G (IVIgG) therapy results in a rapid reversal of thrombocytopenia in over 80% of children with acute immune thrombocytopenic purpura (ITP). Comparable results were observed in eleven infants with an analogous condition, neonatal autoimmune thrombocytopenia (NATP), who received IVIgG (2 g/kg body weight) administered alone (n = 6) or in combination with steroids (n = 5). The median platelet count pre-IVIgG therapy was 25 X 10(9)/l (range 5 to 74 X 10(9)/l). The overall response rate to IVIgG therapy, administered alone or in combination with steroids was 75% (12 of 16 treatment episodes). A good response to therapy was defined as an increase in the platelet count to greater than or equal to 50 X 10(9)/l and at least twice the pre-treatment value at 48 h after completion of the IVIgG infusion. The rapid and generally excellent response to IVIgG therapy in infants with NATP suggests that this treatment approach should be considered as first-line therapy for severely thrombocytopenic infants with this self-limiting but potentially serious disorder.

Autoimmune Diseases↗
PubMed1989

Mineral homeostasis and bone mass in children treated for acute lymphoblastic leukemia.

Clinical observations of bone pain, abnormal gait, and unusual fractures during remission of leukemia led us to assess mineral status in a cohort of 16 children with acute lymphoblastic leukemia treated with intensive chemotherapy. During maintenance and 6 months after the completion of therapy, blood and urine were analyzed for calcium and magnesium and blood for osteocalcin, vitamin D, and parathyroid hormone. Bone mineral content and bone width of the distal one third of the radius of the nondominant arm was measured by single-photon absorptiometry. During therapy, mild ionic hypocalcemia (less than 1.19 mmol/L) and hypomagnesemia (less than 0.77 mmol/L) were demonstrated in 9 and 8 of 16 children, respectively; hypercalciuria (8/16) and hypomagnesiuria (12/16) were also observed. Plasma osteocalcin values correlated with plasma magnesium levels (r = 0.54; p less than 0.05). Oral magnesium supplements normalized plasma magnesium, calcium, and osteocalcin levels, all of which were normal at the postchemotherapy study. Plasma 1,25-dihydroxyvitamin D levels were nondetectable (less than 8 ng/ml) in 12 of 13 patients receiving therapy and in 7 of 14 patients not receiving therapy; alkaline phosphatase activity increased significantly after therapy (179 +/- 86 to 340 +/- 101 units/L), and parathyroid hormone levels were normal in both studies. Bone mineral content/bone width ratio was less than 1 SD below the mean for age- and sex-related population standards in 70% of patients. These data indicate that alterations in magnesium, calcium, and vitamin D metabolism in children treated for acute lymphoblastic leukemia may be instrumental in inducing or sustaining altered bone turnover during chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

A case of CD3+, CD4-, CD8-, WT31- acute T-cell leukemia.

The article reports a case of acute T-cell leukemia (T-ALL) with the unusual CD3+, WT31 phenotype. On surface marker analysis, the blast cells were found to be CD7+, CD2-, CD5-, CD1-, CD4-, CD8-, CD3+ and negative for B-lymphoid and myeloid lineage. The cells had both TCR beta and TCR gamma gene rearrangement but had negative results with the monoclonal antibody WT31, which reacts with a framework epitope on the T alpha/beta heterodimer (Ti) of the conventional T-cell receptor (TCR). This suggests an association of the CD3 molecular complex with a different polypeptide (the alternate TCR gamma). In two similar reported cases of T-ALL (WT31-, CD3+, CD4-, CD8-), the CD3 molecular complex was found to be associated with a product of the T gamma gene.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

An analysis of ultrafiltration during acute peritoneal dialysis in rats.

Transport into and from the peritoneal cavity is effected through separate membranes. Peritoneal function is the sum of the contributions of these membranes. The peritoneal dialysis membranes are defined as intestinal viscera and mesentery, parietal lining membrane, and liver and diaphragm. The present study was undertaken to determine which of these membranes participate in ultrafiltration during peritoneal dialysis. Studies were performed in rats using a hypertonic (1200 mOsm/L) dialysate solution containing 5.6% glucose, 2.8% amino acid, and electrolytes. Both intact and eviscerated rats were studied. The experiments were repeated in animals whose diaphragms were fibrotic and densely adherent to liver. Preparation of the diaphragm did not impact upon ultrafiltration. Ultrafiltration in controls (54 vs. 56 ml with and without a fibrotic diaphragm respectively) and in eviscerated groups (44 vs. 45 ml with and without a fibrotic diaphragm respectively) were not significantly different. However, controls had significantly more ultrafiltration than did eviscerated animals (p less than 0.01). The parietal viscera accounted for 56-59% of the ultrafiltration. This study demonstrates that both the intestinal viscera and parietal walls participate in ultrafiltration.

Animals↗
PubMed1989

Anticoagulant effects of heparin in neonatal plasma.

Available data on the anticoagulant effects of heparin in neonatal plasma are scarce and conflicting: relative to adult plasma, neonatal plasma has been reported to show both resistance as well as sensitivity to heparin. We explored this apparent paradox by comparing how well heparin accelerated inhibition of exogenous thrombin and prevented thrombin generation in defibrinated neonatal and adult plasmas. Using amidolytic assays, we determined the effects of heparin on 1) the neutralization of exogenous human alpha-thrombin and on 2) the formation of endogenous thrombin activity after contact activation and recalcification. Neonatal plasma proved resistant to heparin (0.05 U/mL) during inhibition of added thrombin (15 NIH U/mL). Inhibition of thrombin in heparinized neonatal plasma became as efficient as in adult plasma only after raising the AT III activity to normal adult values. However, de novo generation of thrombin activity was very susceptible to inhibition by heparin, even in neonatal plasmas with physiologically low AT III levels. Peak thrombin activity generated in neonatal plasma in the absence of heparin was 50% or less of peak adult activity, and this already reduced ability of neonatal plasma to generate thrombin activity upon prothrombin activation was further decreased by heparin (0.05-0.2 U/mL). We conclude that due to the neonatal AT III deficiency, added thrombin is inactivated less effectively by heparin in neonatal than in normal adult plasma. Yet, the generation of thrombin activity is impaired in neonatal plasma and easily suppressed by heparin. We speculate that newborn infants may be resistant to heparin therapy during overt thrombotic disease, when neutralization of abnormal thrombin activity is the therapeutic goal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗