Sewer workers: occupational risk for hepatitis C--report of two cases and review of literature.

Two sewer workers contracted hepatitis C. The epidemiological literature in which sewer-contaminated water is described as a known vector for outbreaks of hepatitis C, as well as the specific occupational history of the two patients described here, suggest that sewer workers may be at increased risk of contracting hepatitis C.

Ammonia exposure: a common cause for sinusitis. A case report and review of the literature.

Sinuses are a part of the upper respiratory system and sinusitis has been well-defined as an inflammation of the mucous membrane. Sinusitis occurs commonly as a result of allergies, polyps, common cold and environmental pollution. Reports of sinusitis secondary to ammonia exposure, while common clinically from a reporting point of view, have not been described extensively in the literature. We describe here a patient who was exposed to ammonia gas and developed chronic relapsing sinusitis. The mechanism of injury and review of the world literature indicate that although common clinically, chronic sinusitis as a result of ammonia exposure has not been described extensively.

Reactive airway disease in patients with prolonged exposure to industrial solvents.

This study examines the effects of volatile organic compounds (VOCs) at the workplace on pulmonary function tests. Forty-two patients with a history of industrial exposure to organic solvents and pulmonary symptomatology were studied. Lung function tests were determined utilizing screening spirometry lung volumes, diffusion capacity and methacholine stimulation test. While only 10-15% of the symptomatic patients had abnormal screening spirometry, 42% of the patients had significantly abnormal methacholine stimulation tests. These data show that exposure to volatile organic solvents is associated with bronchial hyperreactivity not commonly detected by screening spirometry and requires methacholine stimulation testing in individuals with unexplained symptomatology and history of exposure to industrial solvents. These findings indicate that the incidence of bronchial hyperreactivity is underestimated in patients with (1) verifiable exposure history to volatile organic compounds known to be pulmonary irritants, (2) pulmonary symptomatology with normal screening spirometry.

Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water.

1. In this study we hypothesized that in individuals with certain genetic makeup, MTBE, benzene or their metabolites act as adducts and may induce programmed cell death. 2. Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene-contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene, for a period of 5 to 8 years. For comparison, we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene. 3. Peripheral blood lymphocytes (PBL) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry. 4. When apoptotic lymphocytes from exposed individuals were compared to apoptotic lymphocytes from the control group, statistically-significant differences between each mean group were detected (26.4 +/- 1.8 and 12.1 +/- 1.3, respectively), indicating an increased rate of apoptosis in 80.5% of exposed individuals (P < 0.0001, Mann-Whitney U-Test). MTBE and benzene-induced apoptosis is attributed to a discrete block within the cell cycle progression. Because cell cycle analysis showed that in PBL from chemically-exposed individuals, between 20-50% of cells were accumulated at the S-G2/M boundaries. 5. One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B (NF-kappa B). NF-kappa B was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene. Indeed, addition of inhibitors of NF-kappa B activation pyrrolidine dithiocarbamate (PDTC), to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40%. This reversal of apoptosis almost to the control level by inhibitor of NF-kappa B activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death.

Methyl tertiary-butyl ether antibodies among gasoline service station attendants.

Occupational exposure to petroleum products (gasoline) and elevated blood levels of MTBE have been demonstrated among gasoline station attendants. While MTBE and its metabolites have been considered environmentally inert, immunologically these materials could be reactive. This study was conducted to assess the immunological reactivity of humans to MTBE. Blood samples from 24 gasoline station attendants and 12 healthy controls were examined for levels of IgG, IgM, IgA, and IgE against MTBE by ELISA. In the gasoline-exposed group 7 out of 24 exhibited optical densities or antibody levels of 3-15-fold (OD 0.6-2.68) of the levels detected in controls (OD < 0.2). The detected antibodies both against MTBE-BSA or MTBE-HSA were of IgG and IgM but not IgA or IgE isotypes. These antibodies at much lower levels (OD of 0.45) were detected in only 1 of the 12 healthy control groups. The specificity of these antibodies was evidenced by absorption of MTBE antibodies in different sera using the same haptenic group bound to a different carrier. These results indicate that immune reactions to MTBE do occur through hapten carrier reactions which, in some individuals, end with specific IgG and IgM production.

Magnesium depletion impairs myocardial carbohydrate and lipid metabolism and cardiac bioenergetics and raises myocardial calcium content in-vivo: relationship to etiology of cardiac diseases.

This study examines the effects of Mg depletion on myocardial bioenergetic, carbohydrate, lipid and phospholipid metabolism. Rats were studied after long-term (12 week) selective dietary restriction of Mg (20% normal dietary intake). Myocardial biopsy samples were examined for glucose 6-phosphate and glycogen to evaluate carbohydrate pathways and for glycerol phosphate and mitochondrial fatty acid oxidation and phospholipid contents to evaluate lipid and phospholipid turnover. Dietary Mg deficiency resulted in falls in myocardial glycogen, glucose-6-phosphate, glycerol phosphate, as well as the contents of phosphatidylcholine (PC), phosphatidylethanolamine (PE), diphosphatidyl glycerol (DPG), phosphatidyl inositol (PI) and total phospholipid phosphorus. These observations demonstrate impaired phospholipid metabolism, probably at the biosynthetic level. The mitochondrial oxidation of long-chain fatty acids was also impaired after Mg depletion. Mg depletion (serum Mg fell 60%) also resulted in significant falls in myocardial [ATP], phosphocreatine (PCr), and Mg with a concomitant rise in myocardial Ca content. These observations are consistent with the tenet that prolonged low [Mg2+]zero can result in marked reduction in oxygen and substrate delivery to the cardiac myocytes, with concomitant changes in membrane phospholipids (potentially resulting in a pro-oxidant state) probably as a result of coronary vasoconstriction.

Silicone breast implants and autoimmunity: causation, association, or myth?

In vivo and in vitro studies, case reports and population studies show that: (1) silicone is immunogenic; (2) silicone is biodegradable and transported via the reticuloendothelial system to distant locations; (3) silicone breast implants "leak" and in turn silicone migrates outside the breast tissue; (4) case reports and population studies document an autoimmune reaction and immunological dysfunction in patients with silicone breast implants; (5) these immunological abnormalities and symptoms are reversible upon removal of the breast implants (in 50-70% of cases). The criteria to establish medical causation are defined, and based on those criteria it is concluded that silicone breast implants cause immunological disease.

Norplant: systemic immunological complications--case report.

The Norplant* system is composed of a set of six Silastic* (silicone polydimethysiloxane) capsules measuring 34 mm by 2.4 mm, each containing 36 mg of levonorgestrel and sealed at either end with a medical grade silicone elastomer adhesive. Levonorgestrel is a synthetic progestin, widely used in combination oral contraceptives and in single-agent "mini-pills". In a procedure completed in less than 15 minutes by an experienced physician, the six capsules are surgically implanted subdermally, most commonly on the inside of the left upper arm. The levonorgestrel diffuses through the Silastic material into the blood stream and is carried to the target organs. Ovulation is suppressed in the majority of the cycles during the first years of use, and cervical mucus is thickened, inhibiting sperm penetration. During use, the effective delivery of levonorgestrel is about 30 mcg/day from day 500 to day 2300. Recently, we have seen patients with complications from Norplant, and we describe here a patient who presented with systemic complications resulting from both the endocrinological aspects of Norplant and the immunological aspects of the Silastic implants. To our knowledge this is the first case report in the western medical literature describing systemic immunological complications as a result of a failed Norplant device.

Antibody to silicone and native macromolecules in women with silicone breast implants.

Silicone implants have been associated with the development of multiple organ system abnormalities, including rheumatic disorders, nervous system, pulmonary dysfunction associated with autoantibodies and abnormalities of cellular immunity. In this regards a number of case reports and series of articles have been described. We hypothesized that an immune reaction to silicone breast implants would include the host reactivity against silicone and the macromolecules within the microenvironment of the implant, and these autoantibodies may react with other tissue antigens far from the site of the implant. To test this hypothesis 520 Symptomatic women with Silicone Implants which have developed Silicone related Immunological disorders and have typically complained of breast pain, Myalgia-Arthralgia, fatigue, or generalized pain, were examined by their physician. Blood samples were obtained and examined for the presence of Silicone antibodies, Myelin Basic Protein and human serum albumin antibodies. These samples were then compared to 520 matched controls without implants. At least at the level of two standard deviation silicone specific antibodies, IgG, IgA IgM, IgE and IgG+IgA+IgM antibodies were detected above the mean of normal controls. When these antibodies were classified based on the specialty of the examining physician, the % of patients with Silicone Antibodies were varied; general practice 51.6, Rheumatology 58.7, and Plastic Surgery 83.3, which may relate to the severeness of the disease. Being that a large % of patients demonstrated very high levels of Myelin Basic Protein Antibodies, possible cross reactive antibodies were sought. However, absorption of highly positive sera for Silicone Antibodies with MBP did not change the levels of Silicone Antibodies. On the other hand, Silicone-HSA was able to reduce the antibody values significantly. This reduction in antibody levels by Silicone is the best indication for the specificity of these antibodies. Moreover when data for silicone antibodies and MBP antibodies was analyzed in patients some with high and others with medium or low levels of silicone antibodies, MBP antibodies did not correspond to the silicone antibody levels. Similarly human serum albumin antibodies which was significantly higher in patients with silicone implants did not correlate with levels of silicone antibodies. These results indicate that immune reaction to silicone and different tissue antigens do occur and they are initiated through different mechanisms. And since predominant antibody class against silicone, MBP and HSA was IgM, clonal activation of IgM is possible which certainly warrants further investigation.

Suppressed natural killer cell activity in patients with silicone breast implants: reversal upon explantation.

We have previously shown that natural killer (NK) 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 significant immunological abnormalities (Vojdani et al., 1992a). Our studies have recently been confirmed by Smith et al. (1994), who described natural killer cell activity suppression following exposure to silicone gel, and reversal upon removal of the gel. This study has been designed to evaluate natural killer cell activities in symptomatic women with silicone breast implants and again after explantation of the implants. Each patient served as her own control. Our findings show a marked significant increase in previously suppressed natural killer cell activity in 50% of the patients. In the other 50%, no change or suppressed NK activity was observed. These findings are compatible with recent studies in experimental animals, which show that administration of silicone reduces natural killer cell activity, and that this is reversible upon removal of the silicone. Since NK cells are important in the control of tumor cell growth, we propose here that patients with reduced NK cell activity are at a higher risk of developing cancer, a concept recently described in experimental animals (Potter et al., 1994; Salhon et al., 1994).

Effect of relatively long-term hypomagnesemia on the chondro-osseous features of the rat vertebrae.

Cartilage and bone in the lumbar vertebrae of magnesium-deficient (LoMg) rats were studied after 4 and 8 weeks of Mg restriction. LoMg animals receiving 0.03% Mg intake had significantly reduced serum Mg levels compared to controls (receiving 0.2% Mg) at both 4 weeks [0.66 +/- 0.06 mg% mean +/- SE (n = 10)] and 8 weeks [0.74 +/- 0.02 mg% (n = 3)] of study. Mean width of the vertebral growth plate was significantly decreased in LoMg animals at 4 weeks [54.7 +/- 3.5 microns (n = 9) vs. control 68.0 +/- 3.0 microns (n = 6)] and 8 weeks [39.5 +/- 2.8 microns (n = 3) vs. control 57.5 +/- 3.6 microns (n = 3)]. The mean number of cells/cartilage column in the growth plate was also less at 4 weeks [5.8 +/- 0.18 (n = 5) vs. control 7.2 +/- 0.19 (n = 5)] and 8 weeks [4.9 +/- 0.19 (n = 3) vs. control 6.2 +/- 0.08 (n = 3)]. A significant proportion of LoMg animals possessed decreased pericolumnar diastase-PAS reactivity at 4 and 8 weeks of study; this indicates a decrease in cartilage glycoprotein content during Mg deficiency. Quantitative histomorphometric analysis determined that vertebral trabecular bone possessed significantly decreased percentage of osteoid surface (2.49 +/- 0.54 vs. control 6.98 +/- 2.8) and significantly decreased percentage of osteoid area (0.18 +/- 0.05 vs. control 0.82 +/- 0.38) after 4 weeks of Mg deficiency. These findings document significant alterations in both bone and cartilage histologic features following relatively long-term Mg deficiency.

Immune functional impairment in patients with clinical abnormalities and silicone breast implants.

Silicone, previously thought to be a biologically inert and harmless material, has now been reported to elicit antibody response and to be responsible for adjuvant disease in humans. The present study was designed to evaluate the immune function of forty individuals who had undergone silicone breast augmentation for a period of longer than ten years and who were compared with 40 sex and age-matched controls. The following immunological functions were studied: lymphocyte subset analysis, lymphocyte mitogenic response, NK cytotoxic activity and markers for autoimmunity such as ANA, rheumatoid factor immune complexes such as smooth muscle, myelin, and thyroid, and tissue antibodies. Results of lymphocyte subpopulation analysis showed significantly elevated T helper/suppressor ratio in 60% and significantly decreased T helper/suppressor ratio in 7.5% of the silicone implant group, while the control group showed increased helper/suppressor ratio only in 10% of tested individuals and no significant decrease in the T helper/suppressor ratio. There was 20% inhibition in T cell mitogenic responses in the silicone implant group, which is significant when compared to the controls. When NK cytotoxic activity was compared between the two groups, significant inhibition in the ability of lymphocytes to kill tumor target cells was observed in the silicone implant group. This inability of target cell lysis was attributed to the demonstrated lack of granularity of NK cells from the silicone implant group. There was significant increase in: immune complexes, anti-nuclear antibodies, anti-thyroid antibodies, anti-striated muscle cell antibody, and anti-myelin basic protein antibodies. These immunological abnormalities in individuals who underwent silicone breast augmentation indicate a mechanism of tissue injury to these patients, causing autoimmune diseases or syndromes. Since autoimmunity in some other conditions is associated with abnormalities in the HLA serotyping system, and since some collagen vascular diseases have been associated with a higher incidence of the HLA serotyping system, it is recommended that HLA studies be included in future investigations of immune-mediated abnormalities associated with silicone breast augmentation. Our findings here show definite abnormalities of the T helper/suppressor ratio, increased autoimmunity, as well as increased production of immune complexes. Silicone implants have been used in cosmetic and reconstructive surgery more than 30 years (Brown et al., 1960). The gel used in the implant is produced from silicone, which is then related with methyl chloride and polymerized to form stable polydimethylsiloxane (Brown, et al., 1960). There have been a number of reports describing the occurrence of connective tissue disease in patients after the implantation of silicone.(ABSTRACT TRUNCATED AT 400 WORDS)

Immune alteration associated with exposure to toxic chemicals.

Immunological abnormalities including lymphocyte subset, lymphocyte immune functional assays, chemical antibodies, and different markers for autoimmune response were examined in individuals exposed to a variety of chemicals in computer manufacturing plants. A comparison of 289 individuals exposed to chemicals to 120 controls revealed that exposed individuals had a significantly higher percentage with either increased or decreased T helper/T suppressor ratios. In addition, the individuals with abnormal T4/T8 ratios demonstrated significant elevation in chemical-hapten antibodies. Therefore, 87 exposed subjects with abnormal T4/T8 ratios were selected for further evaluation by lymphocyte phenotypic expression and T cell, B cell, NK activity, and autoimmune markers, and were compared to 60 controls. The comparison of exposed individuals with controls indicated elevation of T cell (CD3), B cell (CD19), and activated T cell (CD10, CD15, CD26, CD38), suppressed T cell and B cell function decreased or increased NK cell cytotoxic activity. Autoimmunity due to chemical exposure was evidenced by elevation of TA1 phenotype frequencies and presence of rheumatoid factor, immune complexes, ANA, and anti myelin basic protein antibodies. We conclude that chemical exposure may induce immune abnormalities including immune suppression and autoimmunity.