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Biomedical subjects

L Mitchell

Publications and source records attributed to L Mitchell.

At least 73 records · Page 4Linked to original sources
PubMed1995

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↗
PubMed1995

Cardiac arrest during pregnancy: maternal-fetal physiology and advanced cardiac life support for the obstetric patient.

Although cardiac arrest in pregnancy is rare, all members of the healthcare team who care for pregnant women should be aware of the maternal adaptations of pregnancy. Also, more women with preexisting medical conditions are attempting pregnancy. Perinatal nurses, especially those practicing in level III (high-risk) perinatal centers should be trained in dysrhythmia recognition and ACLS protocols. Rapid intervention sometimes can save two lives.

Female↗
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

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

Role of whole-cell pertussis vaccine in severe local reactions to the preschool (fifth) dose of diphtheria-pertussis-tetanus vaccine.

OBJECTIVE: To estimate the contribution of whole-cell pertussis vaccine to severe local reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine. DESIGN: Double-blind randomized controlled trial. SETTING: Urban community. PARTICIPANTS: Volunteer sample of 200 healthy children 4 to 6 years old who were eligible for the fifth dose of DPT vaccine. INTERVENTIONS: Children received, in both arms, either diphtheria toxoid-tetanus toxoid (DT) and monovalent pertussis vaccines (group A, 99 children) or DPT and meningococcal vaccines (group B, 101 children). All were licensed products from single lots. The children were assessed 24 hours later by a trained observer. Serum samples obtained before vaccination were tested for antibodies to tetanus and diphtheria toxins and five pertussis antigens by means of enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of severe local reactions (an area of redness or swelling or both of 50 mm or greater) 24 hours after vaccination. Relation between serum antibody levels before vaccination and rates of severe local reactions to corresponding vaccines. RESULTS: All of the subjects were followed up 24 hours after vaccination. Severe redness was present in 38% given DPT vaccine, 29% given intramuscular pertussis vaccine and 9% given DT vaccine (p < or = 0.002, three-way comparison). Severe swelling was common after vaccination with all three products. After intramuscular pertussis vaccination a relation was evident between the prevaccination levels of antibody to whole-cell pertussis bacteria and the rates of redness (p < 0.02) but not between the prevaccination subcellular antibody levels and the rates of redness. CONCLUSION: That pertussis vaccine resembled the DPT vaccine in causing severe redness suggests that it is the principal cause of such reactions after DPT vaccination. The DT vaccine was also reactogenic; thus, cumulative sensitization to one or more of its constituents may be a factor.

Antibodies, Bacterial↗
PubMed1994

Combining benchmarking with other quality tools to achieve breakthroughs in admitting.

BACKGROUND: A cross-industry benchmarking study in which St Joseph's Regional Health Systems participated recommended that the admissions process (that is, preverifying insurance, obtaining demographic information) be completed before patients arrive at the hospital. To apply this best practice at St Joseph's, management established three team efforts. IMPROVING PREVERIFICATION. One team was assigned to improve the insurance preverification process. After cross-training staff to carry out preverification and piloting a electronic, on-line preverification system, the team increased St Joseph's preverification rate from 2% to 70% for scheduled patients. EXPLORING SEAMLESS REGISTRATION: After exploring solutions for an on-line system that will be integrated across the St Joseph system, the team recommended expanding the current computer system to include all entities and to integrate demographic and clinical information. In addition, a subteam reduced the number of registration forms patients must fill out from eight to one. REDESIGNING ADMISSIONS/REGISTRATION. As part of its restructuring effort, St Joseph's is redesigning six core processes, including admissions/registration. This redesign team is currently implementing two recommendations from the benchmarking study: express admitting and centralized scheduling. LESSONS LEARNED: Organizations are advised to understand the process in its current state by collecting data and working toward improvement goals--and to be prepared for changes in job functions and allocation of resources. Other recommendations are offered to organizations attempting to apply best practices from a benchmarking study.

Admitting Department, Hospital↗
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

An alternative method of occlusal registration for functional appliances.

Although wax is commonly used to record the protrusive occlusal registration for functional appliances, it is not without its disadvantages. In restorative dentistry silicone occlusal registration materials have been developed to overcome some of the drawbacks of wax. This paper presents a method of utilizing these new materials in orthodontics.

Humans↗
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↗
PubMed1994

Thrombin regulation in congenital heart disease after cardiopulmonary bypass operations.

Children with cyanotic congenital heart disease who undergo operation with cardiopulmonary bypass are at increased risk of thromboembolic or hemorrhagic complications, or both. Regulation of thrombin, a key enzyme in coagulation, is essential in preventing these complications. We therefore examined the in vitro capacity of plasma from 15 children with cyanotic congenital heart disease to generate thrombin and to inhibit 125I-thrombin before and after cardiopulmonary bypass. We also assessed whether thrombin had been generated in vivo by assaying levels of fibrinogen, thrombin-antithrombin III complexes, and D-dimer. Plasma levels of the thrombin inhibitors, antithrombin III, alpha-2-macroglobulin, and heparin cofactor II were also measured. Thrombin regulation was normal before operation. After cardiopulmonary bypass, the in vitro capacity to generate thrombin decreased by 50%, and this was primarily a result of hemodilution (31%). Similar postoperative decreases were noted in the levels of antithrombin III, heparin cofactor II, and alpha-2-macroglobulin (26% to 45%). However, the total in vitro plasma thrombin inhibitory capacity decreased by only 13%. Levels of thrombin-antithrombin III and D-dimer increased after operation, indicating that thrombin had been generated and inhibited in vivo. Clinically, there were no thromboembolic complications although six patients required replacement therapy for excessive small-vessel bleeding. In conclusion, thrombin regulation is significantly altered after cardiopulmonary bypass. Although thrombin is generated in vivo, the total residual capacity to do so is impaired because of hemodilution. Despite a concomitant decrease in thrombin inhibitor levels, the total residual in vitro capacity of plasma to inhibit thrombin is relatively spared. This suggests that after cardiopulmonary bypass the risk of hemorrhagic complications after an additional hemostatic challenge is relatively greater than the risk of thrombotic complications. This might be reflected in the predominance of hemorrhagic complications in our patients.

Adolescent↗
PubMed1993

Plasma dermatan sulfate proteoglycan in a patient on chronic hemodialysis.

A 68-year-old man on chronic hemodialysis for 6 years, presented with a spontaneous psoas muscle hemorrhage. Investigations showed intermittently elevated activated partial-thromboplastin time and thrombin time. Preliminary investigations suggested a heparin-like inhibitor in the patient's plasma, but no anti-Xa activity could be detected. Investigation of the ability of patient plasma to inhibit exogenous thrombin showed that most thrombin was inhibited by heparin cofactor II, in contrast to normal plasma in which most thrombin was inhibited by antithrombin III. Treatment of plasma with glycosaminoglycan-degrading enzymes suggested the presence of dermatan sulfate (DS) in patient plasma. This was confirmed in a heparin cofactor II-dependent antithrombin assay for DS that showed anticoagulant equivalent to 2.2 +/- 0.3 micrograms/mL (mean +/- SD) of porcine mucosal DS. Of this activity, approximately 90% was sensitive to enzymes that degrade DS. The glycosaminoglycan containing fraction of plasma was isolated and subjected to gel chromatography. Anticoagulant activity eluted from Sephadex G-100 (Pharmacia, Montreal, Quebec, Canada) as two peaks with Kav of 0.10 and 0.45. After treatment with base, the Kav of the higher molecular weight species was increased to 0.55. This activity was completely sensitive to enzymes that degrade DS. Thus, the active DS was present as a proteoglycan. The lower molecular weight material was not sensitive to enzymes that degrade DS or heparan sulfate and it was active in the heparin cofactor II-dependent antithrombin assay but not in an antithrombin III-dependent antithrombin assay. This activity was not degraded by heating. Subsequently, measurement of DS activity was performed in plasmas obtained from eight other patients on hemodialysis before administration of heparin that showed that all patients had DS activity present that varied from 0.05 to 0.4 microgram/mL. No enzyme-resistant activity could be shown in these patients. In summary, a circulating anticoagulant with properties of DS is present in patients requiring hemodialysis.

Aged↗
PubMed1993

Quantitative organic acid analysis in cerebrospinal fluid and plasma: reference values in a pediatric population.

Quantitative reference values for the concentrations of organic acids in cerebrospinal fluid (CSF) and plasma, as well as ratios of individual organic acids between CSF and plasma, were determined in twenty-three pairs of samples from pediatric patients. Twenty-six organic acids were present and quantifiable in all or the majority of plasma and CSF specimens (limit of detection 1 mumol/l). There were substantial differences between subgroups of organic acids, best reflected by the ratios of individual acids between CSF and plasma. Metabolites related to fatty acid oxidation were present in CSF in substantially lower amounts than in plasma. Organic acids related to carbohydrate and energy metabolism and to amino acid degradation were present in CSF in equal or slightly lower amounts than in plasma. Finally, some organic acids were found in substantially higher amounts in CSF than in plasma, e.g. glycolate, glycerate, 2,4-dihydroxybutyrate, citrate and isocitrate. Quantitation of organic acids in CSF and plasma should aid diagnosis and monitoring of treatment of patients with organic acid disorders.

Acids↗
PubMed1993

Displacement of a mandibular canine following fracture of the mandible.

Much has been written on the aetiology of impacted maxillary canines, but ectopic mandibular canines, being a rarer anomaly, have attracted much less attention. This report describes a case in which the probable aetiology of the displacement of a lower canine was a mandibular fracture through the developing crypt.

Adolescent↗
PubMed1993

English yew poisoning in 43 cattle.

Thirty-five privately owned 1- to 2-year-old mixed-breed steers and heifers, weighing 340 to 454 kg, died from accidental ingestion of English yew (Taxus baccata). Estimated dosages ranged from 0.36 to 0.70 g of fresh plant/kg of body weight. Clinical signs of poisoning and death began 2 to 3 hours after first exposure, and cattle continued to have clinical signs, which ended in death 6 to 8 hours later. Most cattle had died by 4 hours after first ingestion. Necropsy of 4 cattle revealed substantial amounts of English yew leaves and small stems in the rumen contents. Grossly, there were areas of hyperemia in the abomasum and small intestine. Histologically, lesions were limited to the lungs and included moderate congestion and interlobular edema. Chemical analysis by thin-layer chromatography of suspected yew plant material from the rumen contents of the 4 necropsied cattle was compared to authentic taxol, and confirmed the presence of taxol in rumen samples.

Animals↗