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Biomedical subjects

S Goodman

Publications and source records attributed to S Goodman.

At least 55 records · Page 3Linked to original sources
PubMed2000

Inter-regional differences and outcome in unstable angina; analysis of the international ESSENCE trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events.

AIMS: Worldwide there is a large variation in outcome (death, myocardial infarction and recurrent myocardial infarction) in patients with unstable angina or non-Q wave myocardial infarction. These variations may be explained by differences in characteristics of the presenting patients. Here we describe differences in patient presentation, treatment protocols and outcome and we investigate their relationship using data from the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events) trial. METHODS: A total of 2981 patients from six countries which enrolled more than 100 patients were included in the present analysis: United States, Canada, Argentina, France, the Netherlands and United Kingdom. Logistic regression analysis was performed to determine the effect of baseline characteristics on regional outcome. RESULTS: At day 30, the lowest triple end-point rate, irrespective of study drug treatment, was noted in the Netherlands (18.9%) and the highest in Argentina (30.5%). A model including the variables age > or = 65 years, prior angina, diabetes, prior aspirin use, ECG changes at baseline and diagnosis of non-Q wave myocardial infarction and dummy variables for Argentina and France resulted in concordance of about 60%. CONCLUSIONS: Inter-regional differences in outcome in unstable angina and non-Q wave myocardial infarction patients can reasonably well be explained by differences in patient characteristics. However, other so far unidentified variables present in Argentina and France also contributed to differences in outcome and their effect warrants further investigation.

Angina, Unstable↗
PubMed2000

High oxygen concentration exacerbates cardiopulmonary bypass-induced lung injury.

OBJECTIVE: To investigate the effect of ventilation with 100% oxygen on lung injury associated with surgery involving cardiopulmonary bypass (CPB). DESIGN: A prospective randomized study. SETTING: University hospital. PARTICIPANTS: Thirty patients undergoing coronary artery bypass graft surgery with CPB. INTERVENTIONS: Patients were randomized to receive 100% oxygen (Oxygen group) or 50% oxygen (Air group) throughout surgery. During CPB, patients' lungs in the Air group were flushed with air and in the Oxygen group with 100% oxygen. MEASUREMENTS AND MAIN RESULTS: Lung injury was evaluated by arterial oxygen tension-inspired oxygen concentration (PaO2-FIO2) ratio and cytokine levels (tumor necrosis factor-alpha and interleukin-8) in blood and bronchoalveolar lavage fluid measured before and after CPB. The lowest PaO2-FIO2 value was observed after 40 minutes following the completion of CPB in both groups. PaO2-FIO2 values 6 hours after CPB were not different from baseline in the Air group but remained lower (359+/-63 mmHg and 298+/-78 mmHg; p = 0.013) in the Oxygen group. Blood cytokine levels rose during surgery in both groups. Bronchoalveolar lavage levels of interleukin-8 did not change, whereas tumor necrosis factor-alpha increased only in the Oxygen group (p = 0.035). CONCLUSIONS: A significant decrease of oxygenation was observed in the early post-CPB period in both groups of patients, with delay in recovery in patients treated with 100% oxygen. A larger increase of the proinflammatory cytokines was found in patients treated with 100% oxygen. High oxygen concentrations during surgery with CPB should be used only when specifically required.

Bronchoalveolar Lavage Fluid↗
PubMed2000

The correlation between presenting ST-segment depression and the final size of acute myocardial infarcts in patients with acute coronary syndromes.

The use of reperfusion therapy in patients with ST elevation acute coronary syndromes had been established. However, reperfusion therapy is usually considered contra-indicated in those with ST depression, despite the knowledge that regional posterior infarction is typically indicated by ST depression maximal in leads V1 to V3 and nonregional subendocardial infarction is typically indicated by marked ST depression maximal in other leads. This study of patients with non-ST-elevation acute coronary syndromes investigates the quantitative relationship between presenting ST depression and final QRS changes in both of these subgroups. The final QRS score was significantly higher (2.44 points) than that of a control group with not ST depression, (1.55 points) in the group with maximal ST depression in V1 to V3 (P = 0.04). However, in the entire population, there was a highly significant correlation (P = .003) between the sum of the presenting ST depression and the final QRS score. Trials of reperfusion therapy will be required to determine if such evolution to electrocardiogram documented acute myocardial infarction can be prevented in patient with marked ST depression acute coronary syndromes.

Case-Control Studies↗
PubMed2000

A controlled study of vigabatrin and visual abnormalities.

AIMS: To assess the visual function in epileptic patients who have received vigabatrin; to compare this with the visual function in similar epileptic patients who have never received vigabatrin; to investigate whether the severity of visual field defect (VFD) is related to the dose of vigabatrin; to consider other factors that may correlate with the severity of VFD. METHODS: 21 consecutive patients who had taken vigabatrin at some time in their lives were enrolled from the epilepsy clinic of the Royal Shrewsbury Hospital and were compared with a group of 11 otherwise similar patients with epilepsy who had never received vigabatrin. One patient taking vigabatrin was excluded from the study because her visual field results were unreliable because of multi-infarct dementia. 15 patients were taking vigabatrin at the time of the study (VC), the other five had taken vigabatrin some time in the past (VP). Each patient underwent static perimetry using either the two point or the three point full field 120 screening program on the Humphrey visual field analyser, followed by an ophthalmic examination to rule out ocular causes for VFDs. The visual fields from each patient were then analysed using a method devised to convert the VFD into percentage defect in both eyes. In patients with known cerebral pathology that may affect the visual pathway, only the unaffected homonymous hemifield was used. RESULTS: Nine of 20 (45%) patients in the vigabatrin group (VC and VP) complained of blurring of vision compared with two of 11 (18%) controls. Four patients (20%) in the vigabatrin group described flickering lights compared with one control (9%). None had a posterior vitreous detachment. Three of 30 (7.5%) eyes in the VC group had distant visual acuity of 6/12 or worse compared with three of 22 (9%) controls and five of 30 (16.7%) had near visual acuity worse than N6 compared with one of 22 (4.5%) in the control group. A mean of 1.73 Ishihara plates were misread in VC patients compared with 0.2 in the VP group and 0.18 in the controls. 11 of 15 (73.3%) patients in the VC group had greater than 10% VFDs as opposed to one of 11 (9.1%) controls (chi(2) test, p=0. 002). In 12 of 15 (80%) VC patients the percentage VFD was greater in the nasal hemifields than the temporal hemifields compared with six of 11 (54.5%) controls. Significant correlation was found between the severity of VFD and the total dose of vigabatrin ingested for the 20 patients exposed to vigabatrin (VC and VP: Spearman correlation coefficient=0.525; p=0.002), for the 15 patients taking vigabatrin at the time of examination (VC: Spearman correlation coefficient=0.568; p=0.002). CONCLUSION: This pilot study suggested that epileptic patients taking vigabatrin are at much higher risk of developing VFDs compared with epileptic patients on other antiepileptic drugs. The total ingested dose of vigabatrin correlated significantly with the severity of VFDs especially in those patients who had not stopped taking vigabatrin. In our group we found that those who had taken a total dose of 1500 g or more of vigabatrin were at risk of developing significant visual field defects.

Adult↗
PubMed2000

Interferon-gamma downregulates ion transport in murine small intestine cultured in vitro.

Effects of IFN-gamma on mammalian small intestinal ion transport were studied in vitro using incubated sheets of murine small intestine in Ussing chambers. In oxygenated standard culture medium containing hydrocortisone and antibiotics, they maintained their short-circuit current (I(sc)) responses to glucose and theophylline for 48 h. Histological examination revealed a 50% diminution of villus height over 36 h but no change in crypts. Height was better maintained during a 36-h incubation of small intestine from SCID mice, suggesting a role for B or T lymphocytes in villus atrophy. Exposure of small intestine to 100 U/ml IFN-gamma for 36 h decreased basal I(sc) by 40% and I(sc) responses to glucose and theophylline by approximately 70%; at 1,000 U/ml for 36 h, IFN-gamma inhibited these I(sc) responses by 90%. An inhibitor of inducible NO synthase did not reverse these effects, suggesting that they are not mediated by NO. Tissue resistance, mucosal K(+) content, and epithelial morphology were not affected. Ouabain-sensitive ATPase activity in homogenates was inhibited 60% by IFN-gamma (100 U/ml for 36 h). IFN-gamma inhibition of I(sc) responses to glucose and theophylline also occurred in SCID mouse small intestine. Thus murine small intestinal sheets can be maintained viable in vitro for at least 48 h, although villus blunting develops (but less so in SCID mouse small intestine). Also, prolonged exposure to IFN-gamma downregulates Na(+)-coupled glucose absorption, active Cl(-) secretion, and Na(+)-K(+)-ATPase activity, effects unlikely to be mediated by enhanced NO.

Animals↗
PubMed2000

G8363A mutation in the mitochondrial DNA transfer ribonucleic acidLys gene: another cause of Leigh syndrome.

We identified a G-->A transition at nt-8363 in the mitochondrial DNA transfer ribonucleic acidLys gene in blood and muscle from a 13-month-old girl who had clinical and neuroradiologic evidence of Leigh syndrome and died at age 27 months. The mutation was less abundant in the same tissues from the patient's mother, who developed myoclonus epilepsy with ragged red fibers (MERRF) in her late 20s. In both mother and daughter, muscle histochemistry showed ragged red and cytochrome c oxidase-negative fibers and biochemical analysis showed partial defects of multiple respiratory-chain enzymes. A maternal half-sister of the proband had died at 2.5 years of age from neuropathologically proven Leigh syndrome. The G8363A mutation, which previously had been associated with cardiomyopathy and hearing loss, MERRF, and multiple lipomas, also should be included in the differential diagnosis of maternally inherited Leigh syndrome.

Adult↗
PubMed2000

Efficacy of postoperative blood salvage following total hip arthroplasty in patients with and without deposited autologous units.

BACKGROUND: Patients undergoing total hip replacement routinely receive perioperative blood transfusions, increasing their risk of blood-borne disease, isoimmunization, anaphylactic reaction, and hemolytic reaction. The purpose of this retrospective, case-control study was to evaluate the effect of postoperative blood salvage on the need for allogeneic transfusion following total hip replacement. METHODS: We reviewed the medical records of ninety consecutive patients who, during a twelve-month period, had undergone unilateral, elective total hip replacement that included use of a postoperative blood salvage device. For comparison, we reviewed the medical records of ninety consecutive patients who had undergone total hip replacement without postoperative blood salvage. Overall, 156 patients had complete medical records and were included in the study. RESULTS: Eight (10 percent) of the patients who had been treated with a drain and seventeen (23 percent) of the patients who had been treated without a drain received allogeneic transfusions. Of the nineteen patients who had not deposited autologous blood, all six without postoperative blood salvage required allogeneic transfusion. With control for other variables in the model, regression analysis showed a significantly increased risk of allogeneic transfusion among patients who had undergone total hip replacement without postoperative blood salvage (p = 0.0028) and without having predonated autologous units (p = 0.0001). CONCLUSIONS: Despite a limited sample size, the study results showed that postoperative blood salvage significantly reduced the risk of allogeneic transfusion among patients managed with total hip replacement, whether or not they had deposited autologous blood (p < 0.0001). With control for donated units, age, gender, preoperative hematocrit, intraoperative blood loss, and cementless technique, patients who were treated without postoperative blood salvage were approximately ten times more likely to require allogeneic transfusion than were patients who had a drain.

Adult↗
PubMed1999

Children with acute lymphoblastic leukemia who receive T-cell-depleted HLA mismatched marrow allografts from unrelated donors have an increased incidence of primary graft failure but a similar overall transplant outcome.

Disparity for HLA in unrelated donor bone marrow transplantation (BMT) increases the risk of graft rejection and graft-versus-host disease (GVHD) and may compromise transplant outcome. We have compared the outcome of matched and mismatched transplants from unrelated donors in 137 children with acute lymphoblastic leukemia (ALL). Their disease status was complete remission (CR)-1, 24 patients; CR-2, 88 patients; CR-3, 18 patients; CR-4, 2 patients; and relapse, 5 patients. CAMPATH monoclonal antibodies were used for T-cell depletion and cyclosporin A was given to 134 children together with short-course methotrexate in 43, mainly when there was HLA disparity. Fifty-two donor/recipient pairs were HLA-mismatched, 41 at HLA-A and -B and 11 at HLA-DR and -DQ loci. Overall graft failure was increased in recipients of marrow mismatched at either HLA-A, -B, -DR, or -DQ (15.7% v 4.8%; P =.057) mainly because there was a higher proportion of children with primary graft failure (11. 8% v 1.2%; P =.012). The presence of an HLA-C locus mismatch did not independently increase the likelihood of graft failure. There was no significant difference in the incidence of acute GVHD >/= grade 2 between the matched and mismatched groups (P =.849). For patients in CR-2, the risk of relapse post-BMT was significantly lower if leukemic relapse occurred off-treatment (P =.005). The Kaplan-Meier overall and leukemia-free survival (LFS) estimates for recipients of matched and mismatched BMT, respectively, at 36 months were 49% versus 42% (P =.380) and 45% versus 40% (P =.654). Although HLA mismatching results in an increased occurrence of primary graft failure with T-cell-depleted allografts, it allows more donors to be identified rapidly for children with ALL without compromising overall transplant outcome.

Adolescent↗
PubMed1999

The characterization of macrophages and osteoclasts in tissues harvested from revised total hip prostheses.

The differentiation and maturation of macrophages and osteoclasts at the prosthetic interface in cases of implant loosening are poorly understood. Using histochemical and immunohistochemical staining methods, we compare macrophage differentiation in tissues from revised hip replacements in patients with specific clinical-radiological appearances. Periprosthetic tissues were harvested from 12 cemented acetabular and 12 cemented femoral components in 24 patients undergoing revision hip replacement. The prostheses were all radiographically and clinically loose. Six acetabular and six femoral components demonstrated radiographic ballooning osteolysis. Serial 6 microm frozen sections of the periprosthetic tissues were processed with hematoxylin and eosin for general tissue morphology, and analyzed for the presence of tartrate resistant acid phosphatase (TRAP, an osteoclast marker). Immunoperoxidase staining using monoclonal antibodies to CD68 (macrophages and osteoclasts) and CD51 (the alpha chain of the vitronectin receptor, an osteoclast marker) was also performed. Approximately 8-30% of the total cells in the tissues were positive for TRAP and the vitronectin receptor, and comprised a subset of the CD68 positive macrophages and macrophage polykaryons. However, there were no statistically significant differences between specific groups (femoral vs. acetabular, osteolysis vs. no osteolysis) for the numbers or percentages of macrophages or osteoclast-like cells. Once prosthetic loosening has occurred, few differences in the macrophage-osteoclast profile of tissues from different periprosthetic locations, with and without osteolysis, are noted. This suggests a final common biologic pathway for periprosthetic bone resorption, once implant loosening has transpired.

Acid Phosphatase↗
PubMed1999

Glutaryl-CoA dehydrogenase deficiency presenting as 3-hydroxyglutaric aciduria.

Two siblings who were found to have deficiency of glutaryl-CoA dehydrogenase were identified by the presence of large amounts of 3-hydroxyglutaric acid in the urine. Patients with this disease, termed glutaric acidemia or glutaric acidemia Type I, usually present with large amounts of glutaric acid in the urine, and amounts of 3-hydroxyglutaric acid found are less. Patients were ataxic and dystonic. Intelligence was normal. 3-Hydroxyglutaric acid in the urine was quantified by organic acid analysis via gas chromatography mass spectrometry (GCMS) and by stable isotope-dilution (internal standard) GCMS. Glutaryl-CoA dehydrogenase activity in cultured fibroblasts was found to be 2% of the control level. The nature of the mutations was identified, and both patients were found to be compound heterozygotes for R227P, which changed an arginine to a proline, and E365K, which changed a glutamate to a lysine.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

PGP9.5 as a candidate tumor marker for non-small-cell lung cancer.

PGP9.5 is a neurospecific peptide that functions to remove ubiquitin from ubiquitinated proteins and prevents them from targeted degradation by proteasomes. Using the serial analysis of gene expression method (SAGE), we observed that the PGP9.5 transcript was highly expressed in primary lung cancers and lung cancer cell lines but was not detectable in the normal lung. Here we examined the expression of PGP9.5 protein in normal lung epithelium, lung tumor cell lines, and 98 resected primary non-small-cell lung carcinomas (NSCLCs). We found PGP9.5 reactivity in normal lung in a pattern compatible with K-cells of the diffuse neuroendocrine system. However, the PGP9.5 was present in both small-cell lung cancer (SCLC) and NSCLC cell lines (22/24) independent of neuronal differentiation. In primary NSCLCs, 54% (53/98) of the cases had positive PGP9.5 staining, and the expression of protein was strongly associated with pathological stage of the cancer. It was present in 44% (29/66) of stage I NSCLCs and in 75% (24/32) of stage II and IIIA NSCLCs (p = 0.0032). These results suggest that the increased expression of PGP9.5 is specifically associated with lung cancer development and may serve as a potential marker for the detection of lung cancer.

Basic Helix-Loop-Helix Proteins↗
PubMed1999

High-dose therapy with autologous or allogeneic transplantation as salvage therapy for small cleaved cell lymphoma of follicular center cell origin.

Between 1985 and 1996, 51 patients with relapsed or refractory small cleaved cell lymphoma (SCCL) received high-dose chemotherapy +/- TBI in conjunction with autologous (ABMT) (36 patients) or allogeneic transplantation (15 patients). Patients were eligible for ABMT if the bone marrow biopsy done prior to the planned transplant did not reveal microscopic involvement with SCCL. Patients receiving ABMT had a median age of 48 years, had received a median of 2.5 chemotherapy regimens prior to transplantation, and were transplanted a median of 35.5 months from diagnosis. Among patients receiving ABMT, 5 year actuarial survival was 56+/-11%. Median survival was 126+ months, and median survival from diagnosis was 191 months. Univariate and multivariate analysis identified sensitive disease as the best predictor of a favorable response. Five-year actuarial survival was 66+/-12% for patients with sensitive disease at the time of transplant as compared to 29+/-17% for patients with resistant disease, P = 0.015. Median survival in patients with sensitive disease at the time of ABMT was 126+ months. By univariate analysis, survival was significantly better for patients receiving ABMT as compared to patients receiving allogeneic transplants. Median survival following allogeneic transplantation was 5 months; 5 year actuarial survival was 15+/-13%. In a multivariate analysis, which considered autologous vs allogeneic transplantation, sensitive vs resistant disease, <3 vs > or = 3 prior treatments, and prior bone marrow involvement, allogeneic transplantation was significantly associated with poor survival. Treatment-related mortality occurred in eight of 15 patients receiving allogeneic transplantation and limited the effectiveness of this therapy. High-dose therapy in conjunction with ABMT is effective therapy for patients with SCCL whose disease is sensitive to chemotherapy and whose marrows are microscopically free of disease. Because of possible selection bias, it has not been proven that this approach increases survival in these patients. Treatment-related mortality limits the effectiveness of allogeneic transplantation in SCCL.

Adult↗
PubMed1999

Telomerase activity and prognosis in primary breast cancers.

PURPOSE: Recent studies associate telomerase activity with prognostic factors and survival. We compared quantitative telomerase activity in primary tumors with traditional prognostic factors and outcome in a group of invasive but nonmetastatic breast cancers. PATIENTS AND METHODS: Telomerase activity was measured in 203 invasive breast cancers by the quantitative telomeric repeat amplification protocol method. Telomerase expression was compared with 28S rRNA level, tumor content, and clinical variables, including outcome. For clinical correlations, telomerase activity was standardized by two methods: (1) a correction for cellularity using 28S rRNA levels, and (2) a correction for the histologically determined invasive proportion of the specimen. RESULTS: Telomerase activity was found in 82% of breast cancers with measurable 28S rRNA levels. Telomerase activity was associated with the proliferative index (P <.01) of the tumor but not with any other prognostic variable. Neither uncorrected nor corrected telomerase activity was associated with relapse-free or overall survival in this study. CONCLUSION: Telomerase activity level was associated with the proliferative index of invasive breast cancers, but its measurement in samples from this group of nonmetastatic breast cancer patients did not predict survival.

Adult↗
PubMed1999

Higher rates of coronary angiography and revascularization following myocardial infarction may be associated with greater survival in the United States than in Canada. The CARS Investigators (Coumadin/Aspirin Reinfarction Study).

BACKGROUND: Significant differences are known to exist between the United States and Canada with respect to coronary catheterization and intervention. In a post hoc analysis, it was hypothesized that these differences may have the greatest impact on outcome in patients at risk for recurrent events such as those following myocardial infarction (MI). PATIENTS AND METHODS: The hypothesis was tested in a nonrandomized comparison of the catheterization and revascularization patterns for patients following acute MI in 7029 patients in the United States and 1774 patients in Canada who participated in the Coumadin/Aspirin Reinfarction Study (CARS). CARS tested the effectiveness of low dose warfarin in combination with acetylsalicylic acid (ASA) versus ASA alone in reducing cardiovascular morbidity and mortality. RESULTS: Before study enrollment (median day 7 to 8), 84.5% of the American patients underwent coronary angiography compared with only 7.7% in Canada (P<0.01). CARS patients in the United States underwent significantly more frequent angioplasty during their hospital admission before study enrollment than their Canadian counterparts (55.8% versus 3.0%, respectively, P<0.01), and there was a more frequent use of intravenous heparin among American CARS patients (96% versus 88%, respectively, P<0.01) but less frequent administration of thrombolytic therapy (44% versus 49%, respectively, P<0.01). For follow-up of up to 32 months, American CARS patients had significantly fewer primary events (cardiovascular deaths, nonfatal MI, nonfatal ischemic stroke) than Canadian patients. Cumulative estimate of a primary end point comparing American with Canadian patients was, respectively, 2.0% versus 3.1% at one month, 8.0% versus 11.3% at one year and 11.6% versus 15.0% at two years. Thus, time to the primary event was significantly longer in American patients (P=0.0001). All-cause mortality estimates at 12 months were 2.2% and 4.0%, respectively, for the American and Canadian CARS subgroups. When management for the index MI (ie, angiography and angioplasty) is included in the model, the risk of death for Canadian versus American subgroups of CARS is not statistically different (0.9, 95% CI 0.6 to 1.2, P=0.40). CONCLUSION: Among study participants, American patients experienced a better outcome than Canadian patients, which may be attributable to more aggressive management based on early coronary angiography and angioplasty. However, angioplasty before study enrollment in American patients may have resulted in enrollment of lower risk patients. This selection bias limits the scope of the comparison.

Aged↗
PubMed1998

Low-molecular-weight heparins in non-ST-segment elevation ischemia: the ESSENCE trial. Efficacy and Safety of Subcutaneous Enoxaparin versus intravenous unfractionated heparin, in non-Q-wave Coronary Events.

Combination antithrombotic therapy with heparin plus aspirin decreases the risk of recurrent ischemic events in patients with acute coronary syndromes without persistent ST-segment elevation. Compared with standard unfractionated heparin, low-molecular-weight heparin (LMWH) has a more predictable antithrombotic effect, is easier to administer, and does not require coagulation monitoring. At 176 hospitals in 3 continents, 3,171 patients with rest unstable angina or non-wave myocardial infarction were randomly assigned to either enoxaparin (a LMWH), 1 mg/kg twice daily subcutaneously, or to continuous intravenous unfractionated heparin, for a minimum of 48 hours to a maximum of 8 days. Trial medication was administered in a double-blind, placebo-controlled fashion. At 14 days, the primary endpoint, the composite risk of death, myocardial infarction, or recurrent angina with electrocardiographic changes or prompting intervention, was significantly lower in patients assigned to enoxaparin compared with heparin (16.6% vs 19.8%; odds ratio [OR] 1.24; 95% confidence interval [CI] 1.04-1.49; p = 0.019). At 30 days, the composite risk of death, myocardial infarction, or recurrent angina remained significantly lower in the enoxaparin group compared with the unfractionated heparin group (19.8% vs 23.3%, OR 1.23; 95% CI 1.0-1.46, p = 0.016). The rate of revascularization procedures at 30 days was also significantly lower in patients assigned to enoxaparin (27.1% vs 32.2%, p = 0.001). The 30-day incidence of major bleeding complication was 6.5% versus 7.0% (p = not significant), but the incidence of minor bleeding was significantly higher in the enoxaparin group (13.8% vs 8.8%, p <0.001) due primarily to injection-site ecchymosis. Thus, combination antithrombotic therapy with enoxaparin plus aspirin is more effective than unfractionated heparin plus aspirin in decreasing ischemic outcomes in patients with unstable angina or non-Q-wave myocardial infarction in the early (30 days) phase. The lower recurrent ischemic event rate seen with the LMWH, enoxaparin, is achieved without an increase in major bleeding, but with an increase in minor bleeding complications due mainly to injection-site ecchymosis.

Adolescent↗
PubMed1998

Kinetic analysis of integrin-dependent cell adhesion on vitronectin--the inhibitory potential of plasminogen activator inhibitor-1 and RGD peptides.

Distinct binding interactions between cell-surface receptors and extracellular matrix components are characteristic of multifunctional adhesion proteins such as vitronectin. The close proximity of binding sites for alpha(v)-integrins and plasminogen activator inhibitor-1 (PAI-1) on vitronectin may have consequences for cell adhesion and migration, or for the localized inhibition of plasminogen activators. In this study, the kinetics and reversibility of vitronectin-dependent cell adhesion via alpha(v)-integrins was investigated using RGD peptides and PAI-1 as competitors. Active, but not latent or cleaved PAI-1, and RGD peptides were effective in preventing cell adhesion to vitronectin provided the inhibitor was present at the time of cell seeding. In a concentration-dependent manner urokinase or thrombin abrogated the inhibitory effect of PAI-1. Following cell seeding onto a vitronectin substratum, delayed addition of RGD peptides or active PAI-1 (10-20 min post-seeding) resulted in the loss of their inhibitory potential. These data were supported by experiments in a purified system where delayed addition of active PAI-1 could no longer prevent vitronectin binding to immobilized alpha(v)beta3, while a cyclic RGD peptide gave some moderate inhibition. The apparent stabilization of vitronectin-integrin contacts was observed with immobilized native or multimeric vitronectin but not with the more rigid form of denatured, aggregated multimers. These results demonstrate that the cell adhesive properties of vitronectin depend on its conformational flexibility and can be tightly regulated in a spatio-temporal manner through direct competition of cellular integrins by soluble or matrix-bound factors such as PAI-1.

Amino Acid Sequence↗
PubMed1998

Composite hip prosthesis design. II. Simulation.

An investigation was performed to study the mechanical performance of fiber-reinforced composite hip prostheses. In Part I of the study, a three-dimensional finite element code was developed for analyzing a composite hip prosthesis in a femur. The material properties of the composite were treated as anisotropic and inhomogeneous while the properties of the femoral bone were treated as anisotropic and homogeneous. All the materials were assumed to behave linear-elastically. Thermoplastic graphite/PEEK material was selected for the study. No slippage was assumed at the interface between the implant and the surrounding femoral bone. In Part II, numerical simulations were performed using the code to study the performance of a composite prosthesis in the femur. The stress/strain distributions, micromotions, and strain energy density of the surrounding femoral bone were evaluated and found to be related to initial fixation and long-term stability of the prosthesis in the femur. Numerous fiber orientations were studied, and the results of the calculations were compared with those generated from a prosthesis made of cobalt chrome and Ti-6Al-4V titanium alloys. Based on the analysis, it was shown that compared to conventional metallic implants more favorable stresses and deformations could be generated in the femur using composite implants. In addition, by changing fiber orientations according to femoral loads, a composite implant could be designed specifically for the left or the right femur.

Computer Simulation↗