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SUPPRESSED NATURAL KILLER CELL ACTIVITY IN PATIENTS WITH SILICONEIMPLANTS: REVERSAL UPON EXPLANTATION BY:ANDREW W, CAMPBELL, M.D., Clinical assistant professor, University of Texas Health Science Center, MedicalDirector, Center For Immune, Environmental and Toxic Disorders, Houston, Texas.NACHMAN BRAUTBAR, M.D., clinical Professor of Medicine, University of Southern California School of Medicine,Medical Director, Center for International Occupational and Toxicological Medicine, Los Angeles, California.ARISTO VOJDANI, PH.D., Associate Professor of Medicine, Drew University School of Medicine and Science,Department of Medicine and Dermatology, Director, Immunosciences Lab, Inc., Los Angeles, California.PUBLISHED, TOXICOLOGY AND INDUSTRIAL HEALTH 10: 3 MAY - JUNE 1994Address all correspondence to: W. , M.D.14441 Memorial Drive, Suite 6Houston, Texas 77079Reprinted with the permission of W. , M.D.SUPPRESSED NATURAL KILLER CELL ACTIVITY IN PATIENTS WITH SILICONE-REVERSAL UPON EXPLANTATION -ABSTRACTWe have previously shown that natural killer cell activity is significantly suppressed in patients with silicone breast implants.These patients were symptomatic and the suppression of natural killer cell activity was associated with additional significantimmunological abnormalities. (1) Our studies have recently been confirmed by Srnith et al., (2) who described natural killercell activity suppression following exposure to silicone gel. and reversal upon removal of the gel.This study has been designed to evaluate the natural killer cell activities in symptomatic women with silicone breast implantsafter implantation and after the explantation of the implants. Each patient served as its own control. Our findings show amarked significant increase in previously suppressed natural killer cell activity. These findings are compatible with the recentstudies in experimental animals, showing that administration of silicone reduces natural killer cell activity. and that this isreversible upon removal of silicone.Since NK cells are important in the control of tumor cell growth we propose here that patients with reduced NK cell activityare at a higher risk of developing cancer. a notion recently described in experimental animals. (3 & 4) *Nachman Brautbar,M.D. to whom all communications should be addressed at: 2222 Ocean View Avenue, Los Angles. California 90057INTRODUCTIONNK cells are sensitive indicators of activation by biologic response modifiers, and their monitoring has been used to documentalteration in the activity of circulating immune cells, Abnormalities in NK cell activities have also been described inAutoimmune Disorders. Most recently, NK cell activities have been shown to be affected in patients exposed to chemicals,and in patients with silicone breast implants.Since the symptomatology of patients with silicone breast implants has been associated with multiple immunologicalabnormalities, including production of autoantibodies.(',',',') stimulation and suppression of T cells, (1) elevation of circulatoryimmune complexes, (1) and since the reversal of symptomology upon removal of the implants has been associated withreversal of the immunological abnormalities, (5 )it is logical to suggest that immunological marker, such as NK cell activity,will follow these patterns: Suppression as a result of exposure to silicone and reversal to normalization upon removal of thesilicone. Indeed, our studies here support this notion and further support the concept of an immune response to silicone breastimplants.PATIENTS AND METHODSForty women who underwent silicone breast implants and were evaluated for symptoms ranging from joint pain, muscle paincentral nervous system symptomatology, skin rashes and myalgias (3) have been studied. Natural Killer cell activities werestudied prior to the explantation and 3 to 15 months after explantation with an average of 8 months: +/- 1.2 S. E.ANALYSIS OF NATURAL KILLER CELL ACTIVITIES Separation of Human PBL Mononuclear cells from patients and controls were separated from the fresh whole blood byFicoll-hypaque density gradient centrifugation (Litton Bionetics, Rockville, MD). The lymphocyte band at the interface wascollected and cells pelleted by centrifugation, washed twice in RPMI- 1640 and suspended in complete medium, consisting ofRPMI-1640 supplemented with 10)% human AB serum, 2mM glutamine, 25mM Hepes (pH 7.2), 50 units penicillin, and 50units streptomycin per mi.NK Cell Cytotoxicity Assay A modified (51)CR-release assay, as described previously, was employed. Briefly, 1X10(4)(51)Cr-labeled K562 target cells (New England Nuclear Corporation, Boston, MA) in 0. I mil CM were added per well inmicroliter plates. Effector cells were pipetted into quadruplicate wells to give effector:target cell ratios of 100: 1, 50: 1 and 25:1. These cells were allowed to interact at 3 7degC for 4 hr in an atmosphere of 5% C02/95% air. (51)Cr-release was determined by centrifuging the plates at 1000 x g for 5 min and harvesting 0.1 ml of the culturesupernatant for counting gamma counter. Total release was determined by adding 100 ul of 1.0% Triton X-100 andspontaneous release by adding labeled target cells alone in CM.The percent "Cr-release was determined by the experimental (R(e)), spontaneous (R(s)). and total (R(t)) release by thefollowing formula:"Cr-release = (R(e)) - (R(s))------- x 100%(R(t))- (R(s))Lytic units (LU) were calculated from effector titration curves, and (1)LU was defined as the number of effector cellsrequired to achieve 20% lysis. LU/ 10(6) is the number of LU in 10(6) effector cells. For assay reproductability,recommended criteria were employed, Statistical analysis of significance utilized the paired + test and the difference of themeans of the of the 2 groups studied.RESULTSTable I shows the individual values for natural killer cell activities prior to explantation and after explantation.There was a marked and significant increase in natural killer cell activity after explantation. Natural killer cell activity was27.00ñ3.0 (S.E.) Prior to explantation and 36.89+- 3,7 (S.E.) after explantation. The average age of implants was 9.5 yearsñ 0.96. P value for the difference of the means between NK cell I and NK cell III was P<0.032.DISCUSSIONPrevious studies reported from our laboratory have shown a significant and marked reduction of natural killer cell activities inpatients with silicone breast implants. (1) This reduction was attributed to direct effect by silicone through activation of cellularor humoral mechanisms secondary to an immune response to adjuvant effects of silicone.The following functions have been ascribed to natural killer cells:1) control of tumor cell growth2) involvement in the control of microbial infections,3) immunoregulatory properties4) involvement in the development of graft versus host disease,5) contributes to the development of some forms of diabetes, and6) involvement in various gastrointestinal diseases. (7) Natural killer cells mediate a non-major histocompatibility complexwith restricted killing against target cells, which are termed "NK susceptible. " This lytic activity can be observed against avariety of neoplastic and viral-infected cells in non-major histocompatibility complex restricted function. Inhibition of naturalkiller cell activity has been described using prostaglandin A and E glucocorticoids and prolactin as well as luteinizing hormone.Exposure of murine or human natural killer cells to agents such as anti-asialo-GNfl or Prostaglandins induce dose-responsesuppression. Other cellular mechanisms have been described in association with suppression of natural killer cells, includingsuppressor cells, which play a physiological role in regulation of NK cell activity in vivo. Most recently, exposure to orgarficsolvents has been shown to cause suppression of NK cell activity and stimulation of several autoantibodies. (8) Our findingshere show that the suppressed activity of the natural killer cells is reversed and improved markedly upon removal of thesilicone implants, indicating that the direct or indirect effect of the silicone breast implants, which caused suppression ofnatural killer cell activities, has been eliminated by removal of the silicone, the causative agent. This was not correlated withthe length of implantation which ranged anywhere from 0.6 to 16 years with an average of 9.5 +- 0.96 years, nor was thiscorrelated with the length of time period from the explantation.Our studies here are in agreement with the studies reported recently by et al., (2) which reported in rats implanted withsilicone gel a marked reduction, in natural killer cell activity, and reversal of this suppression immediately following removal ofthe implants.Our studies here demonstrate clearly that symptomatic patients with silicone breast implants significantly are associated with amarked reduction of natural killer cell activity, and that this reduction is improved upon removal of the silicone breastimplants. The issue of cancer development in patients with silicone breast implants has not been addressed at the molecularlevel, nor has it been addressed at the clinical level.Recent studies (9) have shown carcinogenicity of silicone in experimental animals. Indeed, these studies were followed by aneditorial calling for epidemiological studies in patients with silicone breast implants to further evaluate the incidence ofhematological malignancy.(10) These investigators did not measure natural killer cell activities in these studies, however,based on our clinical studies here, and on the experimental studies by et al, (2) it is strongly suggested that onemechanism contributing to the carcinogenicity is the reduced activity or inhibition of natural killer cells. The actual mechanismsby which silicone inhibits NK cell activity is not clear. Additional studies at the molecular level are required to furtherunderstand the mechanism of suppression of NK cell activity by silicone.Our studies described here indicate that silicone does inhibit the functions of natural killer cell activities and that this inhibitionis reversible, however, may be associated with reduction of ability to control tumor cells, and in those patients who havechronic reduction of natural killer cell activity, may be associated with carcinogenicy. We propose clinical studies to find theincidence of cancers in patients with silicone breast implants.

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jafras4uak <krcheat@...> wrote:

Has anyone used Dr.

Oh and Dr. Srukant in Seattle (Federal Way) at St.Francis Hospital?

Hi kristin ~

I am one of Dr. Oh's patients. I had lapband surgery on August 2nd so I'm not a

seasoned veteran yet, but I was very happy with Dr. Oh.

If you want to email me off the board with any questions I'd be happy to answer

them.

I'm at audreyhoover at .

Audrey

Dr. Oh Federal Way, WA

banded 08/02/05

295/245/150ish

---------------------------------

FareChase - Search multiple travel sites in one click.

[Guest guest]

Hi Kristi,

If your insurance covers NWWLS, then thank your lucky stars!!! My mom just

self-paid to go there, and the both the surgeons and follow-up care are

excellent.

Three years ago I flew to France rather than go to Dr. Oh. He is a good

surgeon but he is much more pro-bypass, and many of his patients (at the

least the ones I have met) can't stand him after a while.

You are very lucky if you can get insurance to pay for Dr. Montgomery or

Watkins!

Sarina Mc

MIDbanded 11/06/02

by Dr. Frering in Lyon, France

215 / 110 / 115

[Guest guest]

>

> I am from Fairbanks and had my lapband with Dr. Watkins Oct. 5th. The clinic

and Dr's

are wonderful there. I have Welfare andPension Insurance and they did pay. I

really

recommend you talk to Dr. Watkins and his staff. Will be going out in November

for my

first fill.