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Understanding work-related upper extremity disorders: clinical findings in 485 computer users, musicians, and others.

Four hundred eighty five patients whose chief complaints were work related pain and other symptoms received a comprehensive upper-body clinical evaluation to determine the extent of their illness. The group had a mean age of 38.5 years. Sixty-three percent of patients were females. Seventy percent were computer users, 28% were musicians, and 2% were others engaged in repetitive work. The time between the onset of symptoms and our initial visit ranged from 2 weeks to over 17 years. A majority sought care within 30 months with the greatest number of them seeking care before 12 months. Fifty nine percent of subjects were still working when seen despite increasing pain and symptoms such as weakness, numbness, tingling, and stiffness. Following a history, a physical assessment utilizing commonly employed clinical tests were performed including evaluation of joint range of motion, hyperlaxity, muscle tenderness, pain, strength, and imbalance. Neurologic tests included Tinel's sign performed in wrist, elbow, tricipital sulcus, and neck and tests for thoracic out syndrome (TOS). Specific tests such as Finkelstein's test for deQuervain's tenosynovitis, Phalen's test for carpal tunnel syndrome and grip strengths were included in the examination protocol. Significant findings included postural misalignment with protracted shoulders (78%), head forward position (71%), neurogenic TOS (70%), cervical radiculopathy (0.03%), evidence of sympathetic dysfunction (20%), and complex regional pain syndrome (RSD) (0.6%). Hyperlaxity of fingers and elbows was found in over 50%, carpal tunnel syndrome in 8%, radial tunnel syndrome in 7%, cubital tunnel in 64%, shoulder impingement in 13%, medial epicondylitis in 60%, lateral epicondylitis in 33%, and peripheral muscle weakness in 70%. We conclude that despite initial presentation distally, work-related upper-extremity disorders are a diffuse neuromuscular illness with significant proximal upper-body findings that affect distal function. While neurogenic TOS remains a controversial diagnosis, the substantial number of patients with positive clinical findings in this study lends weight to the concept that posture related neurogenic TOS is a key factor in the cascading series of physical events that characterize this illness. A comprehensive upper-body examination produces findings that cannot be obtained through laboratory tests and surveys alone and lays the ground work for generating hypotheses about the etiology of work related upper-extremity disorders that can be tested in controlled investigations.

Adolescent↗

Blockade of the Fas-triggered intracellular signaling pathway in human melanomas is circumvented by cytotoxic lymphocytes.

Fas and Fas ligand (FasL) have been found both in lymphoid and in non-lymphoid malignancies, and are thought to play a role in the interplay between tumors and the immune system. Here we investigated Fas/FasL expression, function and intracellular signalling pathways in human melanomas. Of 5 melanoma cell lines, 3 expressed Fas at their surface, and all of them expressed FasL. FasL was functional, since it triggered Fas-induced apoptosis of human T lymphocytes clones. Conversely, cross-linking of Fas molecule with a specific monoclonal antibody failed to induce apoptosis in any of the melanomas tested, or ceramide intracellular accumulation or caspase-3 activation, pointing to an early alteration in the Fas-triggered signaling cascade. All melanomas retained the ability to undergo apoptosis induced by cytotoxic lymphocytes, which was mediated by the granule exocytosis mechanism. This suggests that melanoma cells evade immune-mediated Fas-triggered apoptosis via a selective blockade of the Fas apoptotic pathway. Cytotoxic lymphocytes, however, may circumvent tumor resistance to Fas-induced death via granzyme-mediated apoptosis, further supporting the development of immunotherapeutic strategies in the treatment of cancer.

Antigens, CD↗

Comparative proteomic analysis to study molecular events during gonad development in mice.

Sex determination represents a critical bifurcation in the road of embryonic development. It is based on a finely regulated network of gene activity, as well as protein-protein interactions and activation or silencing of signaling pathways. Despite the identification of a number of critical genes, many aspects of the molecular cascade that drives the differentiation of the embryonic gonad into either a testis or an ovary remain poorly understood. To identify new proteins involved in this cascade, we employed two-dimensional gel electrophoresis and mass spectrometry to compare the protein expression profiles of fetal mouse testes and ovaries. Three proteins, hnRPA1, TRA1, and HSC71, were found to be expressed in a male-specific manner and this expression was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization. Moreover, HSC71 was found to be hyperphosphorylated in male compared to female gonads, emphasizing the advantage of the proteomic approach in allowing the detection of posttranslational modifications.

Animals↗

From first class to third class: recent upheaval in antiarrhythmic therapy--lessons from clinical trials.

In recent years, the results of large randomized and controlled trials of antiarrhythmic agents for primary and secondary prevention of ventricular tachycardia and ventricular fibrillation have changed perceptions of the actions of antiarrhythmic agents regarding both efficacy and risk. The premature termination of the CAST trials of primary prevention in postinfarct patients highlighted the proarrhythmic risk and inefficacy of the sodium channel blockers (class I action), encainide, flecainide, and moricizine, in patients at relatively low risk for death in the long term. The excess mortality with therapy was attributed to proarrhythmia due to facilitation of reentry, especially during acute ischemia. About the same time, European trials with amiodarone, a complex agent with antiadrenergic action and powerful action to prolong refractoriness (class III action), indicated enhanced survival after infarction with amiodarone but not with agents with class I action. Recent verbal reports of larger and placebo-controlled trials (EMIAT and CAM-IAT) confirm a significant reduction in arrhythmia mortality, possibly with a favorable trend in total mortality. While an older trial with dl-sotalol (class III and beta-blocking actions) showed a trend toward improved survival after infarction, a recent trial with d-sotalol in patients with recent infarction or remote infarction and heart failure was prematurely terminated because of excess mortality attributed to proarrhythmia (torsades de pointes), indicating the importance of beta-blocking properties of a class III agent. A secondary prevention trial (ESVEM) in patients surviving an episode of VT or VF showed significant superiority of dl-sotalol compared to an array of agents that block sodium channels with respect to both efficacy and tolerance. Occurrence rates of arrhythmias treated with drugs tested for efficacy either by suppression of inducible arrhythmias or by suppression of spontaneous ectopy were higher and equivalent for both testing methods. A secondary prevention trial of amiodarone and multiple agents that block sodium channels in survivors of cardiac arrest (CASCADE) showed a significant increased efficacy of amiodarone but poorer long-term tolerance compared with the other agents. Comparative analysis of the results of the various trials suggests that class III action coupled with antiadrenergic action is more efficacious in both primary and secondary prevention of life-threatening ventricular arrhythmias and that lethal proarrhythmias may be the predominant effect in attempts at primary prevention in low-risk populations due to class I or so-called pure class III action.

Adrenergic beta-Antagonists↗

Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty.

BACKGROUND: In-vitro studies indicate that platelet function and the coagulation cascade are impaired by hypothermia. However, the extent to which perioperative hypothermia influences bleeding during surgery remains unknown. Accordingly, we tested the hypothesis that mild hypothermia increases blood loss and allogeneic transfusion requirements during hip arthroplasty. METHODS: Blood loss and transfusion requirements were evaluated in 60 patients undergoing primary, unilateral total hip arthroplasties who were randomly assigned to normothermia (final intraoperative core temperature 36.6 [0.4] degrees C) or mild hypothermia (35.0 [0.5] degrees C). Crystalloid, colloid, scavenged red cells, and allogeneic blood were administered by strict protocol. FINDINGS: Intra- and postoperative blood loss was significantly greater in the hypothermic patients: 2.2 (0.5) L vs 1.7 (0.3) L, p < 0.001). Eight units of allogeneic packed red cells were required in seven of the 30 hypothermic patients, whereas only one normothermic patient required a unit of allogeneic blood (p < 0.05 for administered volume). A typical decrease in core temperature in patients undergoing hip arthroplasty will thus augment blood loss by approximately 500 mL. INTERPRETATION: The maintenance of intraoperative normothermia reduces blood loss and allogeneic blood requirements in patients undergoing total hip arthroplasty.

Adult↗

The recursive deterministic perceptron neural network.

We introduce a feedforward multilayer neural network which is a generalization of the single layer perceptron topology (SLPT), called recursive deterministic perceptron (RDP). This new model is capable of solving any two-class classification problem, as opposed to the single layer perceptron which can only solve classification problems dealing with linearly separable sets (two subsets X and Y of R(d) are said to be linearly separable if there exists a hyperplane such that the elements of X and Y lie on the two opposite sides of R(d) delimited by this hyperplane). We propose several growing methods for constructing a RDP. These growing methods build a RDP by successively adding intermediate neurons (IN) to the topology (an IN corresponds to a SLPT). Thus, as a result, we obtain a multilayer perceptron topology, which together with the weights, are determined automatically by the constructing algorithms. Each IN augments the affine dimension of the set of input vectors. This augmentation is done by adding the output of each of these INs, as a new component, to every input vector. The construction of a new IN is made by selecting a subset from the set of augmented input vectors which is LS from the rest of this set. This process ends with LS classes in almost n-1 steps where n is the number of input vectors. For this construction, if we assume that the selected LS subsets are of maximum cardinality, the problem is proven to be NP-complete. We also introduce a generalization of the RDP model for classification of m classes (m>2) allowing to always separate m classes. This generalization is based on a new notion of linear separability for m classes, and it follows naturally from the RDP. This new model can be used to compute functions with a finite domain, and thus, to approximate continuous functions. We have also compared - over several classification problems - the percentage of test data correctly classified, or the topology of the 2 and m classes RDPs with that of the backpropagation (BP), cascade correlation (CC), and two other growing methods.

Journal Article↗

Fibrinolytic profiles in patients with small cell carcinoma of the lung.

1. Elevated levels of fibrinogen were observed in 100% of untreated patients with SCCL. The elevated fibrinogen tended to normalize with complete remission in response to combination chemotherapy. 2. FDPs were increased in 33% of patients in the limited disease group and in 37% in the extensive disease group. Elevated levels of D-dimers were seen in 26% in the limited disease group and in 50% in the extensive disease group. Levels of FDPs did not parallel levels of D-dimers. Some cases of very advanced disease showed increases in both FDPs and D-dimers. 3. When FDPs were within normal limits, D-dimers tended to be elevated. 4. Levels of plasminogen, alpha 2-antiplasmin, and plasmin were and remained within normal limits throughout the course of treatment, while concentrations of FDPs and D-dimers increased. 5. Plasminogen, alpha 2-antiplasmin, plasmin, FDPs and D-dimers did not show any trend. 6. Peripheral blood measurements did not reflect the crucial role of plasmin in modulating blood fibrinolysis and the metastatic cascade. 7. Evidence of the action of the fibrinolytic system at tumor sites failed to correlate with results of laboratory tests.

Carcinoma, Small Cell↗

Mitogenic responses of vascular smooth muscle cells to lipid peroxidation-derived aldehyde 4-hydroxy-trans-2-nonenal (HNE): role of aldose reductase-catalyzed reduction of the HNE-glutathione conjugates in regulating cell growth.

Products of lipid peroxidation such as 4-hydroxy-trans-2-nonenal (HNE) trigger multiple signaling cascades that variably affect cell growth, differentiation, and apoptosis. Because glutathiolation is a significant metabolic fate of these aldehydes, we tested the possibility that the bioactivity of HNE depends upon its conjugation with glutathione. Addition of HNE or the cell-permeable esters of glutathionyl-4-hydroxynonenal (GS-HNE) or glutathionyl-1,4-dihydroxynonene (GS-DHN) to cultures of rat aortic smooth muscle cells stimulated protein kinase C, NF-kappaB, and AP-1, and increased cell growth. The mitogenic effects of HNE, but not GS-HNE or GS-DHN, were abolished by glutathione depletion. Pharmacological inhibition or antisense ablation of aldose reductase (which catalyzes the reduction of GS-HNE to GS-DHN) prevented protein kinase C, NF-kappaB, and AP-1 stimulation and the increase in cell growth caused by HNE and GS-HNE, but not GS-DHN. The growth stimulating effect of GS-DHN was enhanced in cells treated with antibodies directed against the glutathione conjugate transporters RLIP76 (Ral-binding protein) or the multidrug resistance protein-2. Overexpression of RLIP76 abolished the mitogenic effects of HNE and its glutathione conjugates, whereas ablation of RLIP76 using RNA interference promoted the mitogenic effects. Collectively, our findings suggest that the mitogenic effects of HNE are mediated by its glutathione conjugate, which has to be reduced by aldose reductase to stimulate cell growth. These results raise the possibility that the glutathione conjugates of lipid peroxidation products are novel mediators of cell signaling and growth.

Aldehyde Reductase↗

Comparison of direct immunostaining and electroimmunoassay for analysis of airborne grass-pollen antigens.

Sensitive pollen-allergic patients have been reported to show allergic symptoms not only during the pollen release of allergenic plants but also both before and after the pollen season. Symptoms before the season are evidently provoked by small-sized particles originating partly from developing pollen grains, partly from other plant parts. After the pollen season, antigenic material settles on various surfaces, which thus form a new source of allergenic material. Measuring the allergen concentrations in indoor and outdoor environments demands an effective sampling method and a rapid and sensitive immunochemical analysis, especially for particles of small-sized fractions which are not detected in microscopic analyses. The efficiency of an ELISA and an immunochemical staining method was tested with monoclonal IgG against Phl p 5, the main grass allergen. The Burkard trap and MPC impactor (Marple personal cascade impactor with six-stage particle size fractionation) were compared. The sampling was carried out in southwestern Finland in the summer of 1994. The number of grass-pollen antigen spots greatly exceeded the simultaneous pollen count, indicating considerable antigen activity outside the pollen grains. The counts were especially high in small-sized fractions after the pollen season, when hardly any airborne pollen was found. Spots and pollen divided according to size were highly intercorrelated, indicating that the threshold values used were appropriate.

Air Pollution↗

Plasma therapy at Klinikum Grosshadern: a 15-year retrospective.

Immediately after the availability of highly permeable membranes in 1979, membrane plasma separation was introduced as a mode of extracorporeal blood purification by the nephrology group at Klinikum Grosshadern of the Ludwig Maximilians University of Munich (F.R.G.). The new therapy was applied primarily in the management of immunologically mediated renal and extrarenal disorders as well as in paraproteinemias. We also have witnessed a widespread application of this extracorporeal treatment as a last resort in otherwise refractory clinical conditions. Over the years, the group at Grosshadern has contributed to the development, as well as to the laboratory and clinical testing, of new plasma separation membranes, simplified plasmapheresis formats (e.g., spontaneous membrane plasma separation), and several plasma fractionation procedures (e.g., cascade filtration, adsorption). Whenever indicated and possible, plasma fractionation procedures, rather than unselective plasma exchange, are performed in an appropriate clinical situation.

Chemical Fractionation↗

In vitro and in vivo antitumor activity of the novel derivatized polyvinyl alcohol-based polymer P10(4).

PURPOSE: The major limitation to successful chemotherapy of neuroblastoma is the toxicity of traditional antitumor drugs. Hence, less toxic and more effective drugs are to be found, and novel formulations of conventional compounds allowing a more favorable biodistribution should be sought for. In an attempt to pursue this task, we recently synthesized an amphiphilic polymer based on a polyvinyl alcohol backbone [P10(4)]. EXPERIMENTAL DESIGN: The cytotoxic activity of P10(4) was evaluated both in vitro on neuroblastoma and melanoma cell lines and in vivo in pseudometastatic neuroblastoma models. Apoptosis was assessed by morphology, cytofluorimetric analysis of DNA content, and DNA fragmentation assay. Caspases activation was investigated by kits specific for caspase-1, caspase-2, caspase-3, caspase-4, caspase-6, caspase-7, caspase-8, caspase-9, caspase-10, and caspase-13. Colony formation was evaluated by soft agar assay. RESULTS: P10(4) exerted a potent cytotoxic activity on different neuroblastoma and melanoma cell lines through induction of both extrinsic and intrinsic caspase cascades and subsequent apoptosis. Moreover, the clonogenic potential of cells that survived P10(4) treatment was strongly reduced. Next, we tested the effects of P10(4) in nude mice injected with both a human and a murine neuroblastoma cell lines i.v. P10(4) significantly increased the life span and the long-term survival of treated mice over controls. No side effects were observed, even at doses higher than those used for therapeutic purposes. CONCLUSIONS: Our data suggest that P10(4) holds promise as an anticancer compound and, because of its lack of interaction with DNA, is unlikely to give rise to drug resistance.

Animals↗

Sphingosine kinase modulates microvascular tone and myogenic responses through activation of RhoA/Rho kinase.

BACKGROUND: RhoA and Rho kinase are important modulators of microvascular tone. METHODS AND RESULTS: We tested whether sphingosine kinase (Sphk1) that generates the endogenous sphingolipid mediator sphingosine-1-phosphate (S1P) is part of a signaling cascade to activate the RhoA/Rho kinase pathway. Using a new transfection model, we report that resting tone and myogenic responses of isolated resistance arteries increased with forced expression of Sphk1 in smooth muscle cells of these arteries. Overexpression of a dominant negative Sphk1 mutant or coexpression of dominant negative mutants of RhoA or Rho kinase together with Sphk1 completely inhibited development of tone and myogenic responses. CONCLUSIONS: The tone-increasing effects of a Sphk1 overexpression suggest that Sphk1 may play an important role in the control of peripheral resistance.

Animals↗

Studies on the antitesticular action of DL-6-(N-2-pipecolinomethyl)-5-hydroxy-indane (PMHI) in the rat.

Both prepubertal and adult rats were treated with a single oral dose of either 60 mg or 120 mg of dl-6-(N-pipecolinomethyl)-5-hydroxy indane maleate (PMHI) per kg of body weight. Their testicular weights were drastically reduced compared with those of the controls. A follow-up, beginning on the third day post-treatment and continuing for a period of 50 days, showed that the body weight growth of PMHI-treated rats was not retarded. The hormonal profile indicated that, except for FSH which showed a transitory elevation in PMHI-treated immature rats, the serum levels of LH, estrogen, and testosterone were indistinguishable from those of the controls. Testicular histology revealed that the spermatogenic process in PMHI-treated rats recovered at a dose-related rate. EM sections of testes of adult rats indicated that cytoplasmic vacuolation appeared in the Sertoli cells 5 h post-treatment. The consequent cascade of arrested spermiogenesis included abnormal acrosomal condensation of spermatids and sloughing of polynucleated spermatids. Some spermatocytes also seemed to be affected, but spermatogonia and Leydig cells remained intact. These results indicate the PMHI acts primarily on Sertoli cells and causes arrest in the spermiogenetic stage of the spermatids. At a higher and toxic dose of PMHI, however, the earlier germinal elements might also be affected, due to the extensive damage to the supporting Sertoli cells.

Age Factors↗

The effects of melatonin in glutamate-induced neurotoxicity of rat cerebellar granular cell culture.

In the present study, melatonin was tested in subsequent doses in glutamate induced neurotoxicity in cerebellar granular cell culture of rat pups. Glutamate at 10(-7) M was found to induce neuronal cell death. The dead cell score was 2.75+/-0.7 in the control, while it was found to be 35.12+/-1.8 in the glutamate-administered group (P<0.0001). Melatonin very potently blocked glutamate neurotoxicity at all doses tested, with 10(-3) M, the highest dose tested, being the most effective. Glutamate may exert a neuroprotective effect by blocking one or more steps of the oxidation cascade in neurons and this effect may be blocked by melatonin.

Animals↗

Amrinone action on guinea-pig isolated stomach fundus.

In the guinea-pig stomach fundus strips, set in cascade, amrinone (3 microM to 0.3 mM) induced contractions which were followed by relaxation only at the highest amrinone concentrations tested (30 mM to 0.3 M). Contractions were transient and scarcely related to the drug concentration used, whereas relaxation was the most pronounced and concentration-dependent effect. The transient contraction elicited by amrinone was abolished by scopolamine, indicating activation of cholinergic receptors, but it was unaffected by low temperature or hemicholinium-3. The relaxing effect induced by amrinone was unaffected by low temperature, by the receptor inhibitors used (scopolamine, phenoxybenzamine, propranolol, methysergide, pyrilamine) and by indomethacin. It was potentiated by dipyridamole (0.1 microM) and completely suppressed by tissue pretreatment with adenosine deaminase (10 U/ml). Inhibition of this effect was also obtained by reducing Ca2+ concentration in the perfusion fluid or by pretreating the preparations with verapamil. These results indicate the involvement of endogenous adenosine in the relaxing effect of amrinone and the requirement of Ca2+ influx through plasma membrane for this effect.

Adenosine↗

Potent and selective inhibitors of leukotriene A4 hydrolase: effects on purified enzyme and human polymorphonuclear leukocytes.

Leukotriene (LT) A4 hydrolase (EC 3.3.2.6) is a bifunctional zinc metalloenzyme that catalyzes the hydrolysis of the unstable epoxide intermediate LTA4 into the proinflammatory substance LTB4 and also exhibits an amidase/peptidase activity toward synthetic substrates. Based on proposed reaction mechanisms for other zinc hydrolases, we have synthesized inhibitors of LTA4 hydrolase and evaluated their effects on the formation of LTB4 from LTA4 using both purified enzyme and intact polymorphonuclear leukocytes. The two most effective inhibitors, an alpha-keto-beta-amino ester (compound IV) and a thioamine (compound VIII), exhibited IC50 values of 1.9 +/- 0.9 and 0.19 +/- 0.12 microM (mean +/- SD, n = 4), respectively. Compounds IV and VIII were also potent inhibitors of LTB4 biosynthesis in ionophore stimulated polymorphonuclear leukocytes with IC50 < 200 nM. At higher concentrations, the biosynthesis of 5-hydroxy-eicosatetraenoic acid was also inhibited with IC50 approximately 10 microM for both substances. In contrast, leukocyte 15-lipoxygenase and platelet LTC4 synthase activity were not inhibited by these substances at the highest concentrations tested, 50 and 10 microM, respectively. Compounds IV and VIII thus exhibit selectivity among enzyme activities in the arachidonic acid cascade. In conclusion, we describe two compounds that are among the most potent and selective inhibitors of LTA4 hydrolase and LTB4 biosynthesis by intact polymorphonuclear leukocytes, described thus far.

Angiotensin-Converting Enzyme Inhibitors↗

Residue at position 331 in the IgG1 and IgG4 CH2 domains contributes to their differential ability to bind and activate complement.

A conserved proline residue is found at position 331 in the CH2 domains of human IgG subclasses which fix complement. This residue is replaced by a serine in IgG4 which is inactive. To determine the role of residue 331 in the differential ability of human IgGs to activate the complement cascade, a pair of genetically engineered anti-dinitrophenol IgG1 and IgG4 antibodies with reciprocal mutations at position 331 were tested for their hemolytic activity as well as for their ability to bind C1q, activate C1 and cleave C4. The IgG1 Ser331 mutant was virtually unable to mediate the lysis of trinitrobenzene-sulfonic acid-derivatized sheep red blood cells as a result of a marked defect in C1q binding activity. In contrast, the substitution of Pro for Ser331 in IgG4 bestowed partial hemolytic activity (40%) to the IgG4 Pro331 variant. Under low ionic strength conditions, this mutant was found to be approximately 50 and 75% as active as wild-type IgG1 in the C1q binding and C4b deposition assays, respectively. These results indicate that residue Pro331, which folds into close proximity to a previously identified C1q binding motif (Duncan, A. R., and Winter, G. (1988) Nature 332, 738-740), contributes to the architecture of the IgG1 C1q binding site and that its replacement by a serine residue in IgG4 is largely responsible for the functional inactivity of this isotype.

Amino Acid Sequence↗

Approaches to the treatment of unstable angina and non-Q wave myocardial infarction.

Multiple clinical trials have been undertaken to understand better the events leading to unstable angina and non-Q wave myocardial infarction. Some of these studies focused on evaluating the role of antithrombotic therapy; others evaluated the role of more aggressive invasive treatment versus medical therapy. In the 1980s and 1990s, studies revealed that antithrombotic therapy with either acetylsalicyclic acid alone or heparin alone was more effective than placebo. The Thrombosis in Myocardial Infarction (TIMI) IIIB study attempted to compare medical therapy with early surgical intervention, reporting that early intervention did not result in any significant improvement in patient outcome over medical therapy. In the mid- to late 1990s, the thrombin hypothesis was introduced, suggesting that thrombin antagonists would arrest the coagulation and thrombotic cascade. The Global Use of Strategies To Open Occluded Coronary Arteries (GUSTO) IIb study put the thrombin hypothesis to the test, and it found that there was no significant difference between hirudin and unfractionated heparin treatments after 30 days. Glycoprotein IIb/IIIa receptor antagonists were then researched in the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC), the c7E3 Fab Antiplatelet Therapy in Unstable Refractory angina (CAPTURE), the Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON) and the Platelet Receptor Inhibition of Ischemic Syndrome Management in Patients Limited to Unstable Angina Signs and Symptoms (PRISM-PLUS) studies, shifting the attention to the platelet. These studies gave contrasting results, bringing to the foreground the issues of optimal use of antithrombotic agents and proper timing of surgical intervention. Medical therapy for unstable angina and non-Q wave myocardial infarction was addressed in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) study, which compared a low molecular weight heparin, enoxaparin, with unfractionated heparin. A significant difference in outcomes was found in favour of enoxaparin.

Angina, Unstable↗