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Biomedical subjects

D Green

Publications and source records attributed to D Green.

At least 73 records · Page 4Linked to original sources
PubMed2000

Ewing's sarcoma of the pelvis. Long-term survival and functional outcome.

Fifty patients with Ewing's sarcoma of the pelvis were treated using a multidisciplinary approach; followup of surviving patients averaged 137 months (range, 40-276 months). The addition of surgical resection to the multidisciplinary treatment for all patients was associated with improved survival compared with survival of patients treated with chemotherapy and radiation therapy alone; the addition of surgery to the treatment regimen of 37 patients without metastases also was associated with improved survival. There were no significant differences between the surgical and nonsurgical groups in terms of tumor size, stage of disease, patient age, duration of symptoms before diagnosis, or anatomic site. Surgery was used more often in recently treated patients, but the year of diagnosis and treatment did not significantly affect overall survival, secondary to large confidence intervals. The Short Form-36 and the Musculoskeletal Tumor Society functional evaluation instruments showed a superior level of function in the nonsurgical group, but this difference was not statistically significant. There have been many advances in the treatment of patients with Ewing's sarcoma during the past 3 decades, resulting in improved survival for patients with Ewing's sarcoma of the pelvis. The addition of surgery significantly improved survival and did not show a significant difference in functional outcome.

Adolescent↗
PubMed1999

Design and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa.

The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(S)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (K(i) = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl(2)-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.

Animals↗
PubMed1999

A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism.

BACKGROUND: Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped. METHODS: In this double-blind study, we randomly assigned patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism to continue receiving warfarin, with the dose adjusted to achieve an international normalized ratio of 2.0 to 3.0, or to receive placebo for a further 24 months. Our goal was to determine the effects of extended anticoagulant therapy on rates of recurrent symptomatic venous thromboembolism and bleeding. RESULTS: A prespecified interim analysis of efficacy led to the early termination of the trial after 162 patients had been enrolled and followed for an average of 10 months. Of 83 patients assigned to continue to receive placebo, 17 had a recurrent episode of venous thromboembolism (27.4 percent per patient-year), as compared with 1 of 79 patients assigned to receive warfarin (1.3 percent per patient-year, P<0.001). Warfarin resulted in a 95 percent reduction in the risk of recurrent venous thromboembolism (95 percent confidence interval, 63 to 99 percent). Three patients assigned to the warfarin group had nonfatal major bleeding (two had gastrointestinal bleeding and one genitourinary bleeding), as compared with none of those assigned to the placebo group (3.8 vs. 0 percent per patient-year, P=0.09). CONCLUSIONS: Patients with a first episode of idiopathic venous thromboembolism should be treated with anticoagulant agents for longer than three months.

Anticoagulants↗
PubMed1999

Autoimmune antibody in a hemorrhagic patient interacts with thrombin-activated factor XIII in a unique manner.

Without a prior history of hemorrhagic disease, a 62-year-old man suffered recurrent episodes of bleeding. Solubility of the patient's clot in 5 mol/L urea indicated a problem with fibrin stabilization. The transamidase activity potential of factor XIII, measured by the incorporation of radioactive putrescine into N,N-dimethylcasein as test substrate, was 62% of control, close to the normal range of values. Examination of the patient's clot from recalcified plasma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that essentially none of the alpha chains and only about two thirds of the gamma chains of fibrin became cross-linked under conditions where both were fully cross-linked in the controls. An antibody to factor XIII was isolated which, although recognizing the recombinant rA2 subunits, as well as the virgin A2B2 plasma ensemble, showed a 100-fold greater affinity for the thrombin-activated rA2' and A2'B2 forms of the zymogen, suggesting that the latter would be its main target during coagulation. Furthermore, the patient's IgG has an ability, never seen before, for inducing an enzymatically active configuration in the thrombin-activated zymogen in the absence of Ca2+.

Antigen-Antibody Reactions↗
PubMed1999

Referral patterns to a University-based cardiac rehabilitation program.

Referral rates to our cardiac rehabilitation program among patients hospitalized for coronary heart disease were computed over an 18-month period. Only 8.7% of eligible patients were referred, suggesting that more education targeting physicians, patients, and insurers is needed and barriers to participation must be systematically addressed.

Adult↗
PubMed1999

Guidelines for assistance to siblings of children with cancer: report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology.

This is the seventh official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, instituted in 1991. This document develops an additional topic discussed and approved by the SIOP Committee, "Assistance to siblings of children with cancer. " It is addressed to the pediatric oncology community and outlines general principles for helping siblings throughout phases of treatment: at diagnosis, during treatment, in the event of relapse, during bone marrow transplantation, after completion of therapy, during palliative care and the terminal phase.

Child↗
PubMed1999

Spontaneous inhibitors of factor VIII: kinetics of inactivation of human and porcine factor VIII.

Autoantibodies to factor VIII (FVIII)(spontaneous inhibitors) often inactivate FVIII in a complex fashion (type II inhibitors) as compared with alloantibodies (hemophilic inhibitors), which usually demonstrate second-order reaction kinetics (type I inhibitors). The infusion of porcine FVIII in patients with spontaneous inhibitors may give rise to anti-porcine FVIII antibodies. The purpose of this study was to determine whether these were type I or type II inhibitors. Plasma from 8 patients with spontaneous inhibitors and 6 patients with hemophilia with inhibitors were studied. Equal volumes of patient plasma and either pooled normal human plasma or porcine FVIII (Hyate-C) were incubated at 37 degrees C for 90 minutes. Aliquots were removed immediately after mixing and at 30-minute intervals and assayed for FVIII by using a two-stage method. The values for residual FVIII were log-transformed and plotted against the time of incubation, and the resultant curves were analyzed for goodness of fit (coefficient of determination, r2) by using linear and exponential equations. The values were examined by paired t tests; P values were two-tailed. Values are expressed as mean +/- SD. The titers of spontaneous inhibitors against human FVIII ranged from 2.6 to 416 Bethesda Units (BU), and those against porcine FVIII ranged from 0.7 to 47 BU. Samples were diluted so that the FVIII levels in the mixtures before incubation were similar: human, 0.44 U/ml; porcine, 0.47 U/ml; P = not significant. Four of the 8 patients with spontaneous inhibitors inactivated human FVIII in a fashion consistent with complex kinetics; their r2 values with the linear equation were less than 0.90. All r2 values improved when the exponential equation was used (linear, 0.90 +/- 0.08; exponential, 0.92 +/- 0.06; P = .007). In contrast, r2 values with porcine FVIII were the same (0.94) with either the linear or the exponential equation (P = not significant). r2 for the 6 hemophilic inhibitors showed no significant difference between the linear and exponential equations; the values were 0.99 with human FVIII and 0.95 with porcine FVIII. In non-hemophilic patients, antibodies developing to porcine FVIII have kinetics of inhibition that are second order (type I), even though antibodies to human FVIII in these same patients may have complex (type II) kinetics.

Animals↗
PubMed1999

Antiphospholipid antibodies, proteins C and S, and coagulation changes in sickle cell disease.

The significance, interactions, and sources of coagulation abnormalities and their relationship to clinical severity and painful episodes in sickle cell disease are not clear. To evaluate this, we have examined various measures of coagulation in 37 patients with sickle cell disease (20 patients with HbSS disease and 17 patients with HbSC disease). Measurements have included isotypes of antiphospholipid antibodies (IgG, IgM, IgA) to specific phospholipids; proteins C (activity, total antigen) and S (activity, total and free antigen); measures of coagulation activation (prothrombin fragment 1.2, thrombin-antithrombin, fibrinopeptide A, d-dimers); indicators of clinical severity; and studies obtained during steady states and painful episodes. Results in HbSS disease showed that antiphospholipid antibodies were increased, with IgG phosphatidylserine showing the highest and most frequently increased levels (37% of patients). Protein C (activity) and protein S (activity, total, free antigen) were decreased (P<.01), and all measures of coagulation activation were increased (P<.001). In HbSC disease, antiphospholipid antibodies were normal, protein C (activity) and protein S (free antigen) were decreased (P<.001), and all measures of coagulation activation were increased (P<.02). A strong correlation was observed in HbSS disease between IgG-PS and d-dimers. Moderate correlations occurred between protein C activity and thrombin-antithrombin and fibrinopeptide A, between protein S activity and prothrombin fragment 1.2 and d-dimers, and between protein C and protein S activity. In HbSC disease, moderate and fewer correlations occurred. Significant differences between HbSS disease and HbSC disease were observed in aPLs, proteins C and S, and measures of coagulation activation. Measurements during steady states and during painful episodes were not significantly different. We conclude that the antiphospholipid antibody IgG-PS may contribute to coagulation activation in HbSS disease and that IgG-PS, protein C, and protein S relate to each other and jointly to measures of coagulation activation. The increased level of IgG-PS in HbSS disease most likely reflects exposure of the procoagulant phosphatidylserine on the surfaces of red cell-shed vesicles and sickle red cells, which would further affect coagulation activation. The significant differences in coagulation measures between HbSS disease and HbSC disease are consistent with differences in clinical severity between the diseases. The development of painful episodes does not appear to be related to the coagulation changes.

Adult↗
PubMed1999

Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus.

OBJECTIVES: The aim of this study was to assess the effect of angiotensin-converting enzyme (ACE) inhibition with enalapril on forearm endothelial function in subjects with type II diabetes mellitus. BACKGROUND: Endothelial function is depressed in the presence of conventional risk factors for atherosclerosis, and various therapies, such as lipid-lowering therapy in hypercholesterolemia, can improve endothelial-mediated vasodilation. ACE inhibition has improved such function in several conditions including type I diabetes, but there is no evidence for a beneficial effect in type II diabetes. METHODS: The influence of enalapril (10 mg twice daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 10 type II diabetic subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gage plethysmography and graded intrabrachial infusion of acetylcholine (ACh), N(G)-monomethyl-L-arginine (LNMMA) and sodium nitroprusside (SNP). RESULTS: Enalapril increased the response to the endothelium-dependent vasodilator, ACh (p < 0.02) and the vasoconstrictor response to the nitric oxide (NO) synthase inhibitor, LNMMA (p < 0.002). No difference was evident in the response to SNP. CONCLUSIONS: In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes.

Acetylcholine↗
PubMed1999

Developmental changes in time estimation: comparing childhood and old age.

Participants from ages 5 to 99 years completed 2 time estimation tasks: a temporal generalization task and a temporal bisection task. Developmental differences in overall levels of performance were found at both ends of the life span and were more marked on the generalization task than the bisection task. Older adults and children performed at lower levels than young adults, but there were also qualitative differences in the patterns of errors made by the older adults and the children. To capture these findings, the authors propose a new developmental model of temporal generalization and bisection. The model assumes developmental changes across the life span in the noisiness of initial perceptual encoding and across childhood in the extent to which long-term memory of time intervals is distorted.

Adolescent↗
PubMed1999

Complications associated with the treatment of haemophiliacs with inhibitors.

To examine the safety profile of products used to treat inhibitor patients unresponsive to factor VIII, a review of published clinical experience was performed. The products evaluated were activated prothrombin complex concentrates (aPCCs), such as AUTOPLEX T, porcine factor VIII and recombinant activated factor VII (rVIIa). Safety characteristics included potential for transmission of infectious agents, anamnesis, thrombogenicity, thrombocytopenia and allergic reactions. While viral transmission has been virtually eliminated, the risk is theoretically higher with plasma-derived products such as aPCC and porcine factor VIII than with rVIIa, although contamination of cultured cells is a concern. Anamnesis occurs with aPCCs and porcine factor VIII, and may induce resistance to further therapy with porcine factor VIII. Thrombosis and disseminated intravascular coagulation are very infrequently reported in patients exposed to aPCCs and rVIIa, and never with porcine factor VIII. The latter is occasionally associated with thrombocytopenia, but this uncommonly limits treatment with this agent. Lastly, allergic reactions occur with about equal frequency with all products, but anaphylaxis is mainly a concern after administration of porcine factor VIII. In conclusion, products currently available are reasonably safe. Considerations such as efficacy, availability, ease of administration and cost must also be considered in making treatment choices.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Usefulness of quantitative heel ultrasound compared with dual-energy X-ray absorptiometry in determining bone mineral density in chronic haemodialysis patients.

BACKGROUND: Reduced bone mineral density (BMD) is associated with renal osteodystrophy and osteoporosis in end-stage renal failure patients. Dual-energy X-ray absorptiometry (DXA) is the standard non-invasive method to assess BMD, but is not always widely available. Quantitative heel ultrasound (QUS) is a mobile, relatively inexpensive, easy to perform and radiation-free method which can predict fractures to the same extent as DXA. This study assessed the usefulness of QUS vs DXA in determining BMD in chronic haemodialysis patients. METHODS: Patients had their BMD at the hip and spine measured by DXA (Lunar Expert). QUS of the left heel (McCue CubaClinical II machine) measured broadband ultrasound attenuation (BUA) and velocity of sound (VOS). Correlations between DXA and QUS parameters were calculated. Receiver operator characteristic (ROC) curves were plotted for BUA and VOS and used to define cut-off points for calculating sensitivities and specificities for BUA and VOS. Femoral neck BMD was applied as the standard for diagnosing osteoporosis (T< or =-2.5) and osteopaenia (T>-2.5 and < or =-1) by WHO criteria. RESULTS: Eighty eight patients (45.5% women), mean age 58+/-17 years, were studied. A total of 19% and 49% had femoral neck BMDs in the 'osteoporosis' and 'osteopaenia' ranges, respectively. There were good correlations between hip BMD and QUS parameters (r=0.68-0.79, P<0.001). Areas under the ROC curves for BUA and VOS in diagnosing 'osteoporosis' were 0.86 and 0.80, respectively. BUA and VOS had sensitivities of 76 and 71% and specificities of 80 and 69%, respectively, for diagnosing 'osteoporosis'. The positive predictive values for BUA and VOS were 48 and 35%, respectively, and the negative predictive values were 93 and 91% respectively. CONCLUSIONS: DXA and QUS parameters were significantly correlated. However, sensitivities and specificities of QUS parameters were not sufficiently high for QUS to be used simply as an alternative to DXA. The relatively high negative predictive values suggest that QUS may reliably screen out patients unlikely to have a BMD in the osteoporotic range. The relatively low positive predictive values, however, mean that subjects classified as osteoporotic using QUS require further investigations such as DXA to confirm the diagnosis.

Absorptiometry, Photon↗
PubMed1999

Risk factors for reduced bone density in haemodialysis patients.

BACKGROUND: Renal osteodystrophy may result in considerable morbidity for patients with end-stage renal disease. Secondary hyperparathyroidism, adynamic bone disease and osteomalacia, the main bony problems in chronic renal failure, may all be responsible for a reduction in bone mineral density (BMD). This can result in an increased fracture risk. By virtue of their age, post-menopausal status (in women), sedentary life-style and treatment (including previous corticosteroids), haemodialysis patients may be expected also to be at risk for developing osteoporosis, but little is known about the relative importance of these factors. METHODS: We report a prospective study examining the prevalence of reduced bone mineral density (BMD) and its association with a wide range of factors, in a heterogenous group of 88 chronic haemodialysis patients. Femoral neck and lumbar BMD were measured by dual-energy X-ray absorptiometry (DXA). Stepwise multiple linear regression analysis was used to identify risk factors associated with low bone mass. RESULTS: Forty three patients (48.9%) had reduced BMD, and in 17 (19.3%) BMD was below the fracture threshold as defined on DXA measurements by the World Health Organization (WHO). The BMD had significant negative associations with age, serum parathyroid hormone (PTH) levels, current gastric acid suppression therapy, female gender, age at menarche and history of previous fracture. Positive associations were found with weight, haemoglobin concentration, average serum phosphate, weekly heparin dose, oral calcium supplementation and history of parathyroidectomy. CONCLUSIONS: We have confirmed the importance of PTH-related bone disease in affecting BMD in haemodialysis patients, but have found that some other factors, which are known to be risk factors for osteoporosis, are also important.

Absorptiometry, Photon↗