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Biomedical subjects

M Andrew

Publications and source records attributed to M Andrew.

At least 109 records · Page 6Linked to original sources
PubMed1995

Circulating dermatan sulfate and heparan sulfate/heparin proteoglycans in children undergoing liver transplantation.

The liver produces dermatan sulfate (DS), heparan sulfate (HS) and heparin glycosaminoglycans (GAG) and in the presence of hepatic disease, tissue levels of the DS GAG increase dramatically. We hypothesized that in children undergoing liver transplantation plasma levels of DS would be increased. Plasma from children undergoing liver transplantation were tested preoperative, intra operative and post operative at 24-48 h, and 1-3 weeks. Fluctuating levels of DS, HS and heparin anticoagulant activity were detected at all timepoints. The anticoagulant activity was purified and gel chromatography of the material displayed a mean Mr 110,000 D. Reductive elimination decreased the mean Mr 24,000 D indicating the activity resides on a proteoglycan (PG). The purified material was subjected to further chromatography and two peaks of anticoagulant activity resolved, compatible with at least two separate PGs, one with DS GAG chains and the additional PG(s) with HS and heparin GAG chains.

Adolescent↗
PubMed1994

Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura.

The most serious complication of childhood acute immune thrombocytopenic purpura (ITP), intracranial haemorrhage, occurs in about 1% of children with platelet counts below 20 x 10(9)/L. We conducted a randomised study to explore three treatment options in this high-risk group. 146 children (> 6 months and < 18 years old) with typical acute ITP and platelet counts of 20 x 10(9)/L or lower were randomised to receive high-dose intravenous immunoglobulin G (IVIgG) 1 g/kg on 2 consecutive days (n = 34), 0.8 g/kg once (n = 35), intravenous anti-D 25 micrograms/kg on 2 consecutive days (n = 38), or oral prednisone 4 mg/kg per day with tapering and discontinuation of prednisone by day 21 (n = 39). The rate of response as reflected by the number of days with platelet counts at 20 x 10(9)/L or lower and the time taken to achieve a platelet count 50 x 10(9)/L or more was significantly faster for both IVIgG groups than for the anti-D group (p < 0.05); the difference between prednisone and IVIgG was significant (p < 0.05) only for the IVIgG 0.8 g/kg group, and responses to the two IgG groups were similar. These differences in response rates were reflected in the percentages of children with platelet counts of 20 x 10(9)/L or lower at 72 hours following the start of treatment: 3% (IVIgG 0.8 g/kg x 1), 6% (IVIgG 1 g/kg x 2), 18% (anti-D), and 21% (oral prednisone 4 mg/kg/day). Treatment-associated toxicities included a fall in haemoglobin with anti-D (to less than 100 g/L in 24% of cases); weight gain with oral prednisone; and fever, nausea, vomiting, and headache with IVIgG. On the basis of these results, intravenous anti-D cannot be recommended as initial therapy for children with acute ITP and platelet counts of 20 x 10(9)/L or lower. A single dose of 0.8 g/kg IVIgG offers the fastest recovery for the least treatment; additional IgG or oral prednisone can be reserved for the one-third of children who continue to have platelet counts of 20 x 10(9)/L or less at 48-72 hours after the start of treatment.

Adolescent↗
PubMed1994

Measles immunization of 2-year-olds in a rural southern state.

OBJECTIVE: To assess the measles vaccine coverage of 2-year-old children living in Mississippi during the national measles epidemic of 1989 and 1990. DESIGN: Survey of 2-year-olds randomly selected from the 1987 birth cohort. The status of measles-mumps-rubella (MMR) vaccination was determined by medical record reviews and family contacts. SETTING: A predominantly rural state in the southeastern United States with a large black minority population (35%) and a low per capital income ($9827 to $12,899). Approximately 80% of MMR immunizations are given by public health service nurses working in nine health districts. SUBJECTS: A total of 2450 preschool-aged children representing 6% of the 1987 birth cohort (n = 41,279). Three hundred forty-one children were considered ineligible, leaving 2109 in the final sample. MAIN OUTCOME MEASURES: Confirmed vaccination by the age of 2 years. Rates of immunization were calculated for the entire state, its health districts, and subgroups based on population density, per capita income, type of clinic visited, and race. RESULTS: The statewide immunization rate was 87% (95% confidence interval, 86% to 88%). Among the nine health districts, rates varied from 79% to 97% (median, 88%). They were similar for white and black children in each health district and within the state as a whole. The level of vaccine coverage was significantly higher in districts with lower population densities (89% vs 85%, P = .02) and in those with higher per capita incomes (89% vs 86%, P = .03). There were four minor outbreaks of measles during 1989 and 1990; half of the cases occurred in unimmunized children too young to receive the MMR vaccine. CONCLUSION: A high rate of measles immunization is attainable among 2-year-olds living in a rural state with a large black minority population and limited economic resources.

Child, Preschool↗
PubMed1994

Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) occur in pediatric patients; however, the incidence, associated morbidity, and mortality are unknown. A Canadian registry of DVT and PE in children (ages 1 month to 18 years) was established July 1, 1990 in 15 tertiary-care pediatric centers. One-hundred thirty-seven patients were identified prospectively and are the subject of this report. The incidence of DVT/PE was 5.3/10,000 hospital admissions or 0.07/10,000 children in Canada. Infants under 1 year old and teenagers predominated with equal numbers of both sexes. DVT were located in the upper (n = 50) and lower (n = 79) venous system, or as PE alone (n = 8). Central venous lines (CVLs) were present in approximately 33% of children with DVT (n = 45). Associated conditions were present in 96% of children and 90% of children had two or more associated conditions for DVT. DVT was diagnosed by venography (n = 83), duplex ultrasound (n = 37), and other combinations (n = 17). Twenty-two of the 31 ventilation/perfusion scans performed were interpreted as high-probability scans for PE. Therapy consisted of heparin (n = 115), thrombolysis (n = 15), surgical removal of a CVL or thrombus (n = 22), and oral anticoagulant therapy (n = 103). Significant bleeding complications did not occur. However, three (2.2%) children died as a direct consequence of their thromboembolic disease; DVT reoccurred in 23 children and postphlebitic syndrome (PPS) occurred in 26. In conclusion, DVTs occur in a significant number of hospitalized children with a mortality of 2.2%. Complications are not hemorrhagic, but thrombotic, and characterized by PE, recurrent disease, and PPS. In contrast to adults, the upper venous system is frequently affected because of the use of CVLs. The frequency of DVT/PE justifies controlled trials of primary prophylaxis in high-risk groups, and therapeutic trials to determine optimal treatment.

Administration, Oral↗
PubMed1994

[Use of antimicrobial agents in Norway 1980-92].

Use of systemic antimicrobial agents in Norway shows a moderate increase from 1980 to 1992, from 13.5 to 16.9 defined daily doses (DDDs) per 1,000 inhabitants per day. Comparing the Nordic countries, the use of these drugs is second lowest in Norway, after Denmark. In relative terms the use of tetracyclines is highest in Norway. Use of co-trimoxazole is also relatively high, while use of macrolides is low. The share of penicillin V and G is highest in Sweden. Several new and important antimicrobial agents have been introduced on the Norwegian market during the period, while almost as many have been withdrawn. Penicillin V and G constitutes the main subgroup. However, the use of tetracyclines is almost as high, for a short period in fact higher. Taking into account the development of drug resistance and adverse events, it is recommended that use of tetracyclines and co-trimoxazole be reduced, mainly to the advantage of penicillins. The use of cephalosporins seems to be reasonable, but penicillins should be considered more often as an alternative. The use of antimycotic and antiviral drugs is low in terms of DDDs. In 1992 the cost of antimicrobial agents for systemic use was in 1992 approx. NOK 400 million, retail price. The largest subgroup, cephalosporins, constituted almost 20%, as against only 2% of DDDs. Antimicrobial agents represent a substantial part of the total drug budget in hospitals. A shift from expensive to cheaper alternatives should be considered as a routine. Moreover, an optimal change from parenteral to oral administration could help to reduce costs.

Anti-Bacterial Agents↗
PubMed1994

Increased endogenous thrombin generation in children with acute lymphoblastic leukemia: risk of thrombotic complications in L'Asparaginase-induced antithrombin III deficiency.

Pediatric patients with acute lymphoblastic leukemia (ALL) are at an increased risk of thromboembolic events. Potential responsible mechanisms include the disease process itself, treatment with chemotherapeutic agents (particularly L-Asparaginase [ASP]), or a combination of the disease and treatment. We studied thrombin regulation in 26 consecutive children with ALL and 14 healthy age-matched controls by: (1) plasma concentrations of prothrombin; (2) plasma inhibition of 125I-alpha-thrombin; and (3) four biochemical markers of in vivo thrombin activation (thrombin complexed to its inhibitor antithrombin III [ATIII; TAT], prothrombin fragment 1.2 (F1.2), activated protein C complexed to the inhibitors alpha 1 antitrypsin [APCAT]), and protein C inhibitor (APC-PCI). Measurements were made at presentation before treatment, after treatment with ASP alone, and during combination chemotherapy with and without ASP. At presentation, the capacity to generate thrombin (reflected by plasma prothrombin concentrations) and the capacity to inhibit thrombin (125I-alpha-thrombin--inhibitor complex formation) were similar in children with ALL compared with that for healthy children. After ASP alone or as part of combination chemotherapy, prothrombin levels were preserved, whereas plasma inhibition of 125I-alpha-thrombin decreased significantly because of a decrease in plasma concentrations of inhibitors, most importantly ATIII. After combination chemotherapy without ASP, plasma concentrations of ATIII and the capacity to inhibit 125I-alpha-thrombin returned to normal values, whereas prothrombin levels increased above control values. Thrombin generation in vivo also differed from healthy controls. At presentation, plasma concentrations of three of four markers of in vivo thrombin activity (TAT, F1.2, APCAT, but not APC-PCI) were increased in children with ALL. Neither ASP alone nor combination chemotherapy with or without ASP significantly altered values of these three markers. In summary, although the in vitro capacity to generate thrombin was preserved, the in vitro capacity to inhibit 125I-alpha-thrombin decreased after ASP therapy. Evidence for increased endogenous thrombin generation was documented in children with ALL at presentation and throughout treatment. We speculate that poor regulation of this thrombin may contribute to thrombotic complications in children with ALL.

Adolescent↗
PubMed1994

Recombinant vaccinia viruses expressing interleukin-5 stimulate an earlier appearance of antibody-secreting cells in the lung.

Interleukin-5 (IL-5) is a cytokine that participates in the regulation of antibody secretion, in particular promoting the secretion of IgA at mucosal sites. In this report, recombinant vaccinia viruses expressing IL-5 have been inoculated into mice and the appearance of antibody-secreting cells in the spleen and lungs investigated. Although vaccinia virus-expressed IL-5 did not increase the level of IgA in serum, antibody-secreting cells, measured in an enzyme-linked immunosorbent spot assay, appeared earlier in lungs when the immunizing virus expressed IL-5. These early B cells secreted either IgM or IgG1.

Animals↗
PubMed1994

Use of codeine analgesics in a general population. A Norwegian study of moderately strong analgesics.

The prescribing of controlled analgesics (codeine, buprenorphine and pentazocine preparations) was studied, using prescriptions from the three pharmacies in the municipality of Tromsø, Norway. All prescriptions dispensed during one year were analysed. The study sample comprised 3083 women (58%) and 2223 men (42%) between 10 and 99 years of age. About 8% of the population had obtained one or more prescriptions of controlled analgesics. Combined codeine preparations were by far the most frequently prescribed subgroups, and the average amount purchased during 1 year was 30 defined daily doses (DDD). The sporadic users were in the majority. A few users had purchased high amounts of controlled analgesics. The prevalence of use, the mean number of defined daily doses of analgesics, and the proportion of 'weekly' drug users was higher in women than men. The prevalence increased significantly with age, from 0.7 to 22.3% in women and from 0.5 to 14.1% in men. The mean number of DDD during one year also increased with age, from 12.6 to 50.6 DDD in women, and from 6.6 to 40.6 DDD in men. The users of buprenorphine and pentazocine differed in several aspects from the codeine users. The highest use of combined codeine preparations was seen in elderly people especially in women. Use of lower codeine doses or intermittent treatment with other drugs e.g. plain paracetamol in adequate doses, may be appropriate alternatives reducing the risk of adverse drug reactions such as nausea and constipation. Monitoring of prescribing and use of controlled analgesics according to certain criteria may uncover possible misuse.

Adolescent↗
PubMed1994

Age-dependent immune response in Merino sheep.

The numerical and functional attributes of populations of lymphocytes were compared in the blood, lymph and skin of young and mature sheep. Young sheep, four to eight months old, had a lower proportion of CD4+ cells in blood, lymph and skin than mature sheep three to six years old. In contrast, B cells and T19+ cells were as prevalent or more prevalent in young sheep as in mature sheep. Blood lymphocytes from young sheep, cultured in vitro produced less interferon-gamma, both spontaneously and in the presence of concanavalin A than did lymphocytes from older sheep. The serum antibody responses of adult sheep to the T cell-independent antigen Brucella abortus lipopolysaccharide (LPS) were greater over a range of antigen doses, suggesting that an apparent excess of antigen could not overcome the relative immune deficiency of young sheep. The adjuvant Quil A corrected the depressed antibody response of young sheep to B abortus LPS, but dextran sulphate did not. The skin contact hypersensitivity of mature sheep to dinitrochlorobenzene was greater. However, the T cell phenotypes present in infiltrates of lymphocytes elicited by the intradermal injection of tetanus and diphtheria, but not tuberculin antigens, were comparable for the two age groups. The capacity of Quil A to raise the antibody responses of both young and mature sheep to a similar titre suggests that it may be possible to overcome the immunological hyporesponsiveness that may contribute to the disease susceptibility of young sheep.

Aging↗
PubMed1994

Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the alpha 1 subunit of the inhibitory glycine receptor.

Startle disease, or hyperekplexia, is characterized by an exaggerated startle reflex and neonatal hypertonia. An autosomal dominant form of the disorder is associated with mutations in the same codon of the alpha 1 subunit of the inhibitory glycine receptor (GLRA 1) resulting in the substitution of an uncharged amino acid for Arg271 in the mature protein. However, recessive transmission is seen in the mouse mutant spasmodic which resembles startle disease phenotypically and is also associated with mutations in Glra 1. We have confirmed the finding of Arg271 mutations in individuals with startle disease in a UK family showing autosomal dominant transmission. In addition we describe an apparently sporadic case, the offspring of a consanguineous mating, who is homozygous for a novel mutation (T1112A) in GLRA 1, which results in the substitution of asparagine for isoleucine at position 244 of the mature protein. This suggests that human startle disease can display recessive as well as dominant inheritance resulting from different mutations in GLRA 1.

Adult↗
PubMed1994

Acquired antithrombin III deficiency secondary to asparaginase therapy in childhood acute lymphoblastic leukaemia.

As improved treatment regimens for acute lymphoblastic leukaemia (ALL) continue to improve survival future, therapy must also take into consideration the many secondary problems. Most of these are the direct result of combination chemotherapy and L-asparaginase (ASP), is an example of a highly effective chemotherapeutic agent with serious side-effects such as thromboembolic events. ASP interferes with protein synthesis resulting in an acquired deficiency of antithrombin III. This review explores the effects of ALL and ASP on haemostasis, and the link between ASP and thromboembolic events in childhood ALL.

Adolescent↗
PubMed1994

Thrombin inhibition by fetal distal lung epithelium is different in fetal and adult plasma.

Intra-alveolar fibrin deposition is a cardinal feature of neonatal respiratory distress syndrome and likely contributes to short-term and long-term morbidity. Previous studies have shown that fetal distal lung epithelial cell (FDLE) surfaces express procoagulant activity when incubated with adult plasma and may therefore provide one mechanism by which fibrin is generated. However, plasma concentrations of prothrombin and thrombin inhibitors differ significantly at birth and during the first weeks of life compared with adult values. Therefore, we measured thrombin-generating capacity and inhibitor complex formation in cord and adult plasma incubated in the presence of FDLE. Although starting cord plasma concentrations of prothrombin were 43% of adult values, the amount of thrombin generated was decreased by only 21%. When cord plasma concentrations of prothrombin were selectively increased to adult values, the amount of thrombin generated surpassed adult plasma by 89%. The latter observations suggested that thrombin inhibition was impaired in cord plasma compared with adult plasma and supplementation of cord plasma with antithrombin III (ATIII) as well as prothrombin returned thrombin generation to adult levels. However, the percentage of thrombin complexed to inhibitors (59%) at the completion of the experiments was similar in cord, cord plus prothrombin, cord plus prothrombin plus ATIII, and adult plasmas. Although a higher proportion of thrombin was inhibited by alpha 2-macroglobulin (alpha 2M) in cord plasma and cord plasma plus prothrombin, this did not compensate for the decreased amount of thrombin inhibited by ATIII. When cord plasma was supplemented with ATIII as well as prothrombin, the proportions of thrombin complexed by the different inhibitors were similar to those of adult plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Heparin therapy in pediatric patients: a prospective cohort study.

Current guidelines for heparin therapy in pediatric patients have been extrapolated from trials in adult patients without rigorous evaluation of efficacy and safety. We prospectively monitored consecutive pediatric patients receiving systemic doses of heparin over 10 mo at one institution using a predetermined nomogram to monitor maintenance therapy. Sixty-five consecutive children; 38 males and 27 females, received systemic doses of heparin. Thirty children had deep venous thrombosis and/or pulmonary embolism; 11 had arterial thrombi, most frequently after diagnostic angiography; and the remaining 24 received heparin prophylactically, for congenital heart disease. Twenty-nine (45%) of the 65 patients were less than 1 y of age and 22 (34%) were 10 y or older. Congenital heart disease was the predominant diagnosis under 1 y and deep venous thrombosis in older children. After a bolus dose of 50 U/kg, 39% of children (n = 30) achieved a minimal level activated partial thromboplastin time (APTT). Sixty-eight percent of children achieved a minimal level APTT by 24 h and 81% by 48 h. For all 65 children, APTT values were within the therapeutic range 43% of the time. APTT values outside the therapeutic range were twice as likely to be low as high. The average amount of heparin required to maintain therapeutic APTT values for children was 22 U/kg/h: 28 U/kg/h for infants < 1 y and 20 U/kg/h for the rest. Bleeding was rare (2%) and mild. Documented recurrent thrombotic disease was more common (7%) with associated morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Thrombin regulation in children differs from adults in the absence and presence of heparin.

The physiologic mechanisms that protect children from thromboembolic complications are not known. We investigated the regulation of thrombin in children because of its central importance to thrombosis. The capacity to generate thrombin in vitro (chromogenic assay) was decreased by 26% in plasmas from children (1-16 yrs; n = 102) compared to adults ([20-45 yrs; n = 20; p < 0.001]). The addition of purified prothrombin to plasmas from children increased thrombin generation to adult values. The capacity of plasmas to inhibit 125I-alpha-thrombin was increased by 21% in children compared to adults (p = 0.020), with significantly more thrombin complexed to alpha 2-macroglobulin (alpha 2M) in children. When DVT occur in children, adult guidelines for heparin therapy are used. At low heparin concentrations (0.1 and 0.2 U/ml), thrombin generation was decreased by 30% in children compared to adults (p < 0.001). At high heparin levels (0.4 U/ml), thrombin generation was negligible in all plasmas. ATIII inhibited over 95% of thrombin in all plasmas in the presence of heparin. In summary, thrombin regulation differs in children from adults and may protect children from thromboembolic complications. When DVT do occur, heparin requirements may differ in children compared to adults.

Adolescent↗