Chapter: Immunology of Silicones Current Topics in Microbiology and Immunology Volume 210, 1996, pp 337-353 Laboratory Studies in Breast Implant Patients: ANA Positivity, Gammaglobulin Levels, and Other Autoantibodies R. I. Lewy MD FACP, E. Ezrailson PhD
Robert Ira Lewy
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ABSTRACT: Abstract Silicone polymers when used in augmentation prosthesis in breast surgery have been associated in the medical literature with various systemic clinical manifestations and abnormal laboratory testing suggestive of an atypical autoimmune disease. The most frequently cited abnormal test result is the antinuclear antibody. The literature regarding thdy then compares the rate of positive antinuclear antibody tests in a case series of 3380 breast implant recipients with historical normal controls, and finds a six-fold increase in relative risk of a positive test. Analysis of the data show that this increased tendency is at least partially a function of duration of implant exposure to a significant degree (p < 0.001), and the same data shows it is not patient age related. Possible explanations of this phenomenon are discussed, including animal studies suggesting that silicone serves as an adjuvant, and therefore might have an effect on immune tolerance in the subject population.

Article: Laboratory findings reveal potential harm of breast implants
R I Lewy
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ABSTRACT: The article Le by Drs Rohrrich and Clark in the September 1993 Texas Medicine (pp 52-58) is most timely in view of the recent announcement of an agreement in principle between implant manufacturers and plaintiffs attornies regarding possible injuries alleged in many lawsuits.To me,the de facto admission of guilt by Dow ...doesn't mesh well with the thrust of the article that .... Still more disturbing are our own findings ...in a series of 230 Implant patients,abnormal,isotopic bone scans were found were found in 47%, often with wrist uptake. Furthermore when Braun MRIs were done, again 47% showed areas of demyelination or vasculitis("UBOs" at age 44 average. Serological testing showed smooth muscle, myelin basic protein, antinuclear and parietal cell antibodies in 66%, 55%, 23% and 25%. I have intentionally not mentioned any patient symptomatology which are systemic and rheumatoid. We can expect contradictory reports ... Until the specialists who see late complications ca gain the ears of the surgeons....
Full-text · Article · Jan 1993 · Texas medicine

Article: Norplant.
R I Lewy
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ABSTRACT: To the Editor: Not surprisingly, the article by Polaneczky et al.1 and the editorial by Hatcher and Trussell indicate a lower rate of discontinuation for Norplant as compared with oral contraceptives. Although it is reassuring to know that there were comparable rates of sexually transmitted diseases in the two groups (since Norplant users may stop using condoms) and that follow-up was better and satisfaction greater in the Norplant group, the mean follow-up for both groups was only 15 months. This is fine for the group using oral contraceptives, but a woefully short time for investigators to draw conclusions about the safety of Norplant users with an expected five-year course. Fifty-five percent of the users studied by Polaneczky et al. reported irregular bleeding,1 and in another study implant removal was associated with substantial pain (24 percent) or with repeated visits, lengthy (>1 hour) procedures, or both (19 percent).2 Most studies of Norplant have had short follow-up periods, as in the above study.2 Longer studies showed higher rates of discontinuation for medical reasons.3 Lipid disturbances have also been reported.4 In one study, only 58.6 percent of subjects continued using the implant after five years; hypertension necessitating the removal of Norplant developed in three, and only one third of the original group opted for reinsertion.5 Furthermore, the long-term teratogenic effects on fetuses born while the mother used Norplant have not been thoroughly explored. Robert Ira Lewy, M.D Baylor College of Medicine, Houston, TX 77030
Full-text · Article · Apr 1995 · New England Journal of Medicine

Article: Role of thromboxanes in vasotonic versus vaso-occlusive angina
R I Lewy
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ABSTRACT: We used a validated radioimmunoassay to examine plasma thromboxane B2 (TxB2) levels in 6 consecutive vasotonic angina (VA) patients, 14 patients with fixed, occlusive coronary artery (VO) disease and 9 healthy volunteers. In the latter groups, basal TxB2 release was absent. However, all 6 VA patients showed basal release. In one, sustained levels of up to 12 pmol/ml over 2 months of clinical instability were found. Daily aspirin rendered TxB2 undetectable with clinical improvement. In a second patient, angina coincided with up to 14 pmol/ml of TxB2 in peripheral blood, and myocardial infarction produced still further increases. The 14 VO patients were then studied by rapid atrial pacing to detect TxB2 release coinciding with pacing-induced angina and myocardial lactate production. All demonstrated significant occlusive disease (2.5 critical lesions per patient). Blood was taken simultaneously from coronary sinus (CS) and brachial artery (BA) catheters for lactate and TxB2 analysis before, immediately after and 10 min after pacing-induced ischemia. Lactate extraction fell from 29.3 +/- 3.7 per cent to -21.1 +/- 12.8 per cent to -74.3 +/- 20.3 per cent during pacing (all p less than 0.01) but was normal in 10 min (25.1 +/- 3.55). CS TxB2 rose from 18 per cent to 204 per cent of control during pacing but was absent after 10 min. BA TxB2 rose from 40 per cent to 132 per cent of control during and after pacing, but was absent after 10 min (p less than 0.05). In VA, TxB2 is uniquely, continuously present in peripheral blood and levels rise further during symptomatic intervals and myocardial infarction. In VO, even CS TxB2 is absent at rest, and rises less rapidly than in VA, even during pacing-induced ischemia. Although antiplatelet agent will block all TxB2 release even in VO, their clinical potential seems greatest in VA.
No preview · Article · Mar 1983 · Archives des maladies du coeur et des vaisseaux

Article: Thromboxane release during pacing-induced angina pectoris: Possible vasoconstrictor influence on the coronary vasculature
R I Lewy · L Wiener · P Walinsky · A M Lefer · M J Silver · J B Smith
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ABSTRACT: The authors developed a radioimmunoassay for plasma thromboxane B 2, the metabolite of the coronary vasoconstrictor thromboxane A 2. To see if thromboxane A 2 is produced during myocardial ischemia, they used atrial pacing to study 14 patients with greater than 75% occlusive coronary artery disease proved by arteriography. Paired samples were taken from the coronary sinus (CS) and an artery (A) for lactate and thromboxane B 2 analysis before pacing. During and after pacing at 140 beats/min, sampling was repeated. Before, during, immediately after and 10 minutes after pacing, percent myocardial lactate extractions (A-CS/A x 100) were 29.3 ± 3.7%, -21.1 ± 12.8%, -74.3 ± 20.3% and 25.1 ± 3.5%, respectively (all changes p < 0.01). Before pacing, five patients had detectable coronary sinus or arterial thromboxane levels. During pacing, 18% and 40% increases occurred in coronary sinus and arterial blood, respectively (0.8 ± 0.1 to 0.9 ± 0.2 pmol/ml, and 0.5 ± 0.2 to 0.7 ± 0.2 pmol/ml). Immediately after pacing, increases of 204% and 132% occurred in the coronary sinus and arterial blood (p < 0.05), respectively (2.3 ± 0.9 pmol/ml and 1.2 ± 0.4 pmol/ml). Ten minutes after pacing, thromboxane B 2 returned to prepacing levels. These data indicate that thromboxane A 2 is produced during pacing-induced myocardial ischemia and could alter regional coronary blood flow.
Full-text · Article · Jul 1980 · Circulation

Article: Effect of Elevated Plasma-Free Fatty Acids on Thromboxane Release in Patients with Coronary Artery Disease
Robert Ira Lewy
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ABSTRACT: Increases in endogenous free fatty acids (FFA) induced by several stimuli are associated with increases in platelet aggregates and platelet factor 4 in man. To determine if thromboxane (TxB) release is also an associated event, we measured plasma FFA and TxB2 levels before and 5 min after bolus injection of 2,500 U of heparin prior to coronary arteriography in 27 patients with angina. Significant increases in FFA occurred in all patients (p less than 0.02) and those with critical lesions (p less than 0.01), while TxB2 levels also rose (p less than 0.02, p less than 0.05, respectively). However, linear regression showed increases in FFA and TxB2 were independent. The observed TxB2 release may be due to lipolysis-induced exposure of vascular collagen or direct inhibition of platelet adenylate cyclase by heparin.
Full-text · Article · Feb 1980 · Haemostasis

Article: Comparison of plasma concentrations of thromboxane B 2 in Prinzmetal's variant angina and classical angina pectoris
R I Lewy · L Wiener · J B Smith · P Walinsky · M J Silver · J Saia
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ABSTRACT: We have reported that thromboxane B 2 is present in plasma of Prinzmetal's angina patients measured by radioimmunoassay but is below detection limits, <0.5pmol/ml, in normals. To determine whether this metabolite of thromboxane A 2 (a coronary vasoconstrictor) is present in the peripheral blood in classical angina pectoris, we studied 14 patients with fixed obstructive coronary artery disease (2.5 lesions per patient) in whom angina was induced by atrial pacing. Thromboxane B 2 at rest was barely detectable (0.53±0.16 pmol/ml), but rose during pacing (0.74±0.18 pmol/ml) and was maximal (p<0.05) 5-10 min after pacing (1.23±0.36 pmol/ml). In eight variant angina patients, resting levels of thromboxane B 2 were not statistically different during spontaneous angina and angina-free intervals (2.83±0.56 and 1.57±0.34 pmol/ml), but the mean 5-10 min after angina was higher than during angina (6.41±1.46 pmol). The means of preanginal, anginal, and postanginal samples were all higher than the corresponding means of the classical angina group, and thromboxane B 2 levels in variant angina patients in the absence of angina, during angina, and 5-10 min after angina were all significantly higher (p<0.025) compared to the classical angina group measured prior to pacing. Unlike the case with variant angina, thromboxane B 2 is indetectable in classical angina pectoris patients at rest. Furthermore, spontaneous angina in variant angina or pacing-induced angina in classical angina pectoris are both followed by increased thromboxane B 2 although the latter responses are smaller. The role of these phenomena in the pathogenesis of coronary artery spasm and ischemia remains to be clarified.
Full-text · Article · Jan 1980 · Clinical Cardiology

Article: Comparison of plasma concentrations of thromboxane B2 in Prinzmetal's variant angina and classical angina pectoris
R. I. Lewy · L. Wiener · J. B. Smith · P. Walinsky · M. J. Silver · J. Saia
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ABSTRACT: We have reported that thromboxane B2 is present in plasma of Prinzmetal's angina patients measured by radioimmunoassay but is below detection limits, <0.5 pmol/ml, in normals. To determine whether this metabolite of thromboxane A2 (a coronary vasoconstrictor) is present in the peripheral blood in classical angina pectoris, we studied 14 patients with fixed obstructive coronary artery disease (2.5 lesions per patient) in whom angina was induced by atrial pacing. Thromboxane B2 at rest was barely detectable (0.537±0.16 pmol/ml), but rose during pacing (0.747±0.18 pmol/ml) and was maximal (p<0.05) 5–10 min after pacing (1.237±0.36 pmol/ml). In eight variant angina patients, resting levels of thromboxane B2 were not statistically different during spontaneous angina and angina-free intervals (2.837±0.56 and 1.577±0.34 pmol/ml), but the mean 5–10 min after angina was higher than during angina (6.41 7±1.46 pmol). The means of preanginal, anginal, and postanginal samples were all higher than the corresponding means of the classical angina group, and thromboxane B2 levels in variant angina patients in the absence of angina, during angina, and 5–10 min after angina were all significantly higher (p<0.025) compared to the classical angina group measured prior to pacing. Unlike the case with variant angina, thromboxane B2 is indetectable in classical angina pectoris patients at rest. Furthermore, spontaneous angina in variant angina or pacing-induced angina in classical angina pectoris are both followed by increased thromboxane B2, although the latter responses are smaller. The role of these phenomena in the pathogenesis of coronary artery spasm and ischemia remains to be clarified.

Article: Leukemia in patients with acquired idiopathic sideroblastic anemia: An evaluation of prognostic indicators
Robert Ira Lewy · Emin Kansu · Thomas Gabuzda
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ABSTRACT: The initial clinical and laboratory data of 25 patients with acquired idiopathic sideroblastic anemia (AISA) were anlayzed. Criteria for accepting the diagnosis were hyperferremia, ringed marrow sideroblasts, ineffective erythropoiesis, and exclusion of associated hematologic disorders. The findings of a mean age at onset of 70 years, increased mean corpuscular volume, relative neutropenia, and occasional splenomegaly at diagnosis corresponded with previous reports. During the followup for a median period of 32 months, 6 patients (25%) transformed to acute myelogenous or myelomonocytic leukemia after widely variable intervals. The initial data base of these patients was compared to that of the remaining 19 patients in order to isolate predictive features. Only a lesser degree of hyperferremia (P < 0.001) made the group going on to leukemia distinctive. The median survival of these patients was 20 months. The median survival of 19 patients not developing leukemia was 72 months for males and 42 months for females . Hemochromatosis was diagnosed in four patients and was a primary or associated cause of death in three. Analysis of the transfusion history suggested that intrinsic iron leading was a major factor in these patients. We conclude that leukemic transformation in AISA is a common, poorly predictable event which required lengthy followup for detection. Hemochromatosis in AISA occurs frequently and shortens the median survival.
Full-text · Article · Aug 1979 · American Journal of Hematology

Article: 19-Hydroxy-prostaglandin E and infertility in human males1
Robert Ira Lewy · Thomas K. Bills · John Dalton · J.Bryan Smith · Melvin J. Silver
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ABSTRACT: We measured the content of 19-hydroxy-prostaglandin E (19-OH-PGE) and prostaglandin E (PGE) in the semen of 10 infertile males by alkaline dehydration, thin layer chromatographic separation and ultraviolet spectrophotometry. 7 fertile males were also studied. In both groups the content of seminal 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) also was measured by thin layer chromatographic separation and highly specific radioimmunoassay. The amounts of 19-OH-PGE and PGE were significantly lower (p < .02, p < .05) in the infertile group than the fertile group. Differences in mean seminal 6-keto-F1 alpha were not significant. The uterine stimulatory actions of 19-OH-PGE demonstrable in the monkey may apply to fertility in man.
Full-text · Article · Jun 1979 · Prostaglandines and Medicine

Article: Detection of thromboxane B2 in peripheral blood of patients with Prinzmetal's Angina
Robert Ira Lewy · J. Bryan Smith · Melvin J. Silver · John Saia · Paul Walinsky · Leslie Wiener
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ABSTRACT: The plasma levels of thromboxane B2 (TxB2) were determined by radioimmunoassay in 6 consecutive patients with Prinzmetal's angina and in 9 healthy volunteers. In the normal group TxB2 was not detectable (= 0.5 pmoles/ml), while in patients with variant angina TxB2 was consistently detected (1.5-140 pmole/ml).
Full-text · Article · May 1979 · Prostaglandines and Medicine