References
This is a list of references, mostly from the MedLine database.

REFERENCE #1

Title: Polymorphonuclear phagocytosis and killing workers exposed to inorganic mercury.

Perlingeiro RC; Queiroz ML

Department of Pharmacology and Hemocentre, State University of Campinas, Faculty of Medical Sciences, UNICAMP, SP, Brazil.

Int J Immunopharmacol, 1994 Dec, 16:12, 1011-7

The ability of neutrophils to phagocytose and kill Candida species as well as the splenic phagocytic function were investigated in workers from a mercury-producing plant. In the neutrophil phagocytosis study, two species of Candida were used since in individuals with myeloperoxidase deficiency neutrophils are unable to kill Candida albicans, while Candida pseudotropicalis can be effectively lysed. Phagocytosis of both antigens and splenic phagocytic function were normal in all the workers studied. However, following ingestion of the organisms there was considerable reduction in the ability of neutrophils from exposed workers to kill both species of Candida, and this was not explained by a mild impairment of phagocytosis. After improvement in the hygiene conditions in the factory, a new evaluation was performed, 6 months later, in the same workers and urinary mercury concentrations were determined monthly in each worker. Despite a significant reduction in urinary mercury concentrations, a greater impairment in the ability of neutrophils to kill C. albicans was observed. The killing of C. pseudotropicalis presented no further impairment when compared to the previous evaluation. These results suggest that impairment of the lytic activity of neutrophils from workers with urinary mercury concentrations within the safe level for exposed population is due, at least in part, to some interference with myeloperoxidase activity. In addition, the mercury-NADPH complex, once formed, could limit the utilization of reduced pyridine nucleotides by NADPH-dependent enzymes such as NADPH oxidase, thereby inhibiting the PMN respiratory burst.

REFERENCE #2

Title : Effects of mercury on human polymorphonuclear leukocyte function in vitro.

Author: Contrino J; Marucha P; Ribaudo R; Ference R; Bigazzi PE; Kreutzer DL

Address: Department of Pathology, University of Connecticut Health Center, Farmington 06032.

Source: Am J Pathol, 1988 Jul, 132:1, 110-8

Abstract: A variety of heavy metals are recognized as environmental pollutants, and although a significant body of literature exists on the acute toxicity of these metals in various tissues, little is known about the effects of metals such as mercury on host defense. Therefore, the effect of mercuric chloride (HgCl2) on human polymorphonuclear leukocytes (PMN) function in vitro was evaluated. The acute toxicity of HgCl2 for human PMN was calculated initially using vital dye exclusion (trypan blue), and lactate dehydrogenase (LDH) release. Concentrations of HgCl2 less than or equal to 10(-6) M did not induce significant LDH release, or uptake of trypan blue. Additionally, HgCl2 at less than or equal to 10(-7) M produced no ultrastructural alterations in the PMN. The effects of HgCl2 on human PMN functions involved in host defense were evaluated next. HgCl2 consistently suppressed human PMN adherence, polarization, chemotaxis, and erythrophagocytosis at concentrations between 10(-6) and 10(-17) M. Because of the established role of oxygen metabolites in host defense, the effects of HgCl2 on human PMN chemiluminescence and H2O2 production were evaluated next. These studies demonstrated that low concentrations of HgCl2 (ie, 10(-9)-10(-15) M) significantly enhanced chemiluminescence, as well as stimulated H2O2 production by the PMN. These studies clearly demonstrate the ability of extremely low levels of HgCl2 not only to suppress various PMN functions involved in host defense, but also to stimulate oxygen metabolism. In vivo, these HgCl2 effects would not only compromise host defense but also promote tissue injury via the local production of oxygen metabolites.

REFERENCE #3

Title: Chronic intestinal candidiasis as a possible etiological factor in the chronic fatigue syndrome.

Author: Cater RE 2nd

Source: Med Hypotheses, 44(6):507-15 1995 Jun

Abstract: The chronic candidiasis syndrome, also known as the Candida-related complex, putatively caused by the overgrowth of Candida albicans in the gastrointestinal tract and secondarily in the genital organs, is briefly described. Patients with this disorder have many of the same symptoms as those with the chronic fatigue syndrome, except for the recurrent flu-like symptoms of the latter disorder. The positive response of a large number of patients with the chronic fatigue syndrome (CFS) to an oral antifungal agent and a diet for intestinal candidiasis has been described by another clinician. There is evidence that Candida albicans infection of the mucous membranes depresses T cell and natural killer (NK) cell function. Similar abnormalities of immune function are found in the CFS. The function of cytotoxic T cells, T helper cells, and NK cells is important in preventing reactivation of infections from Epstein-Barr virus, cytomegalovirus, and other herpesviruses. Reactivation of one or more of these viruses could lead to the expression of the flu-like symptoms in the CFS. Yet the immune dysfunction found in this disorder has been considered the primary underlying causal factor. It is proposed that chronic intestinal candidiasis may be an agent which leads to immune depression in many CFS patients and therefore that it could be a causal factor in CFS.

Language: Eng

Unique Identifier: 96038377

MESH Headings: Antifungal Agents TU ; Candida albicans GD/IP ; Candidiasis DT/IM/*PP ; Fatigue Syndrome, Chronic DT/*ET/MI ; Human ; Intestinal Diseases DT/IM/*MI/PP ; Models, Biological ; Virus Activation

Publication Type: JOURNAL ARTICLE

ISSN: 0306-9877

Country of Publication: ENGLAND

CAS Registry Number: 0 (Antifungal Agents)

REFERENCE #4

Title: Hypersensitivity pneumonitis related to a covered and heated swimming pool environment.

Author: Moreno-Ancillo A; Vicente J; Gomez L; Mart´in Barroso JA; Barranco P; Caba~nas R; L´opez-Serrano MC

Address: Section of Allergology, La Paz General University Hospital, Madrid, Spain.

Source: Int Arch Allergy Immunol, 114(2):205-6 1997 Oct

Abstract: Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis is a lung disease caused by a large group of inhaled antigens of various sources. The most common HP occurring in the farm environment is classically caused by exposure to various thermophilic actinomycetes and fungi that can grow in the farm environment. Pullularia species and thermophilic actinomycetes have been involved in HP related to humidifier water and saunas. Our case illustrates the value of a site visit in the diagnosis of HP. During a visit to the covered and heated swimming-pool where our patient used to swim we could see that favourable conditions to fungal growth existed. To determine the possible aetiological agents of a suspected HP, cultures from several parts of the swimming-pool were taken. These cultures showed an intense growth of thermophilic actinomycetes, Neurospora and Aspergillus species. Precipitating antibodies against Neurospora species and Mycropolyspora faeni were detected. A case of HP related to a covered and heated swimming-pool environment is reported. Thermophilic actinomycetes and Neurospora species may be the causing agents.

Language: Eng

Unique Identifier: 97478321

MESH Headings: Actinomycetales IP ; Adult ; Alveolitis, Extrinsic Allergic DI/*ET ; Antibodies, Fungal BL ;: Case Report ; Environmental Microbiology ; Fungi IM/IP ; Heating ; Human ; Male ; Precipitin: Tests ; Swimming Pools *

Publication Type: JOURNAL ARTICLE

ISSN: 1018-2438

Country of Publication: SWITZERLAND

CAS Registry Number: 0 (Antibodies, Fungal)

REFERENCE #5

Title: Altered porphyrin metabolism as a biomarker of mercury exposure and toxicity.

Author: Woods JS

Address: Department of Environmental Health, University of Washington, Seattle, USA.

Source: Can J Physiol Pharmacol, 74(2):210-5 1996 Feb

Abstract: Changes in urinary porphyrin excretion patterns (porphyrin profiles) have been described in response to a variety of drugs and chemicals. The present studies were conducted to define the specific changes in the urinary porphyrin profile associated with prolonged exposure to mercury and mercury compounds. In rats, exposure for a prolonged period to mercury as methyl mercury hydroxide was associated with urinary porphyrin changes, which were uniquely characterized by highly elevated levels of 4- and 5-carboxyl porphyrins and by the expression of an atypical porphyrin ("precoproporphyrin") not found in urine of unexposed animals. These distinct changes in urinary porphyrin concentrations were observed as early as 1-2 weeks after initiation of mercury exposure, and increased in a dose- and time-related fashion with the concentration of mercury in the kidney, a principal target organ of mercury compounds. Following cessation of mercury exposure, urinary porphyrin concentrations reverted to normal levels, consistent with renal mercury clearance. In human studies, a comparable change in the urinary porphyrin profile was observed among subjects with occupational exposure to mercury as mercury vapor sufficient to elicit urinary mercury levels greater than 20 micrograms/L. Urinary porphyrin profiles were also shown to correlate significantly with mercury body burden and with specific neurobehavioral deficits associated with low level mercury exposure. These findings support the utility of urinary porphyrin profiles as a useful biomarker of mercury exposure and potential health effects in human subjects.

Language: Eng

Unique Identifier: 96303184

MESH Headings: Adult ; Animal ; Biological Markers UR ; Central Nervous System Diseases CI/UR ; Chelating Agents PD ; Comparative Study ; Dentistry ; Environmental Monitoring ; Human ; Male ; Mercury *AE/*TO/UR ; Methylmercury Compounds TO ; Occupational Exposure *AE ; Porphyrins *UR ; Rats ; Support, U.S. Gov't, P.H.S. ; United States ; Unithiol PD

REFERENCE #6

Thursday October 15 5:56 PM EDT

Chronic fatigue syndrome common in US

NEW YORK, Oct 15 (Reuters) -- Chronic fatigue syndrome is a serious public health concern, affecting about 500,000 Americans, according to a new survey by researchers at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.

The study shows that the disorder occurs in both sexes and all racial and ethnic groups, but is most common in Caucasian women. The rate of chronic fatigue syndrome is ``25 times the rate of AIDS among women... and is considerably higher than female lung cancer... breast cancer... and hypertension,'' said Dr. William C. Reeves, lead author of the study and director of the Viral Exanthems and Herpesvirus Branch of the CDC's National Center for Infectious Disease.

Symptoms of chronic fatigue syndrome (CFS) include debilitating fatigue, memory and concentration difficulties, sore throat, tender lymph nodes, muscle and joint pain, recurrent headaches, sleep disorders, and fatigue lasting more than 24 hours after exertion. Symptoms must persist for 6 months and there must be no other medical explanation for the symptoms in order for physicians to diagnose CFS.

The cause of the syndrome has yet to be determined. While some believe the ailment has a physical basis, others speculate that psychological problems may trigger the disorder.

To determine the prevalence of CFS, Reeves and his colleagues at the CDC conducted a telephone poll involving residents of over 34,000 households in Sedgwick County, Kansas. Respondents were asked to answer a series of detailed questions about their personal medical histories.

Based on the survey results, the authors estimate that about 183 of every 100,000 adult US citizens has a constellation of symptoms fitting the definition of CFS.

The CFS incidence among women is 303/100,000, the researchers report. They found that disease rates were highest of all among white women, at 458/100,000.

Reeves believes that these rates are comparatively high in relation to the incidence of other diseases in the population. For example, he noted that ``three times more women have CFS than HIV infection.''

``This study indicates that CFS affects women and men of all racial and ethnic groups, as well as adolescents,''Reeves said. ''However, white women have the greatest risk for disease and this must be taken into account in planning allocation of health resources and searching for risk factors.''

There are currently no effective treatments for CFS, although one drug, Ampligen, is under review by the US Food and Drug Administration.

For more information about the illness, the advocacy group Chronic Fatigue and Immune Dysfunction Syndrome Association of America can be accessed at www.cfids.org.

REFERENCE #7

Title: Whole-body imaging of the distribution of mercury released from dental fillings into monkey tissues [see comments]

Author: Hahn LJ; Kloiber R; Leininger RW; Vimy MJ; Lorscheider FL

Address: Department of Radiology, University of Calgary, Faculty of Medicine, Alberta, Canada.

Source: FASEB J, 4(14):3256-60 1990 Nov

Abstract: The fate of mercury (Hg) released from dental "silver amalgam tooth fillings into human mouth air is uncertain. A previous report about sheep revealed uptake routes and distribution of amalgam Hg among body tissues. The present investigation demonstrates the bodily distribution of amalgam Hg in a monkey whose dentition, diet, feeding regimen, and chewing pattern closely resemble those of humans. When amalgam fillings, which normally contain 50% Hg, are made with a tracer of radioactive 203Hg and then placed into monkey teeth, the isotope appears in high concentration in various organs and tissues within 4 wk. Whole-body images of the monkey revealed that the highest levels of Hg were located in the kidney, gastrointestinal tract, and jaw. The dental profession's advocacy of silver amalgam as a stable tooth restorative material is not supported by these findings.

Language: Eng

Unique Identifier: 91032709

MESH Headings: Animal ; Comparative Study ; Dental Amalgam * ; Diagnostic Imaging ; Gastrointestinal System ME ; Jaw ME ; Kidney ME ; Macaca fascicularis ; Male ; Mercury *PK ; Mercury Radioisotopes ; Support, Non-U.S. Gov't ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon

Publication Type: JOURNAL ARTICLE

ISSN: 0892-6638

Country of Publication: UNITED STATES

CAS Registry Number: 0 (Mercury Radioisotopes); 7439-97-6 (Mercury); 8049-85-2 (Dental Amalgam)

REFERENCE #8

Re: Dopamine beta hydroxylase and poisons ( lead, mercury, manganese etc. )

Title: Biochemical markers of neurotoxicity. A review of mechanistic studies and applications.

Author ": Manzo L; Artigas F; Martínez E; Mutti A; Bergamaschi E; Nicotera P; Tonini M; Candura SM; Ray DE; Costa LG

Address: Toxicology Unit, University of Pavia, Italy.

Source: Hum Exp Toxicol, 1996 Mar, 15 Suppl 1:, S20-35

Abstract: Neurotoxicology presents major challenges to the development of biological markers in accordance to conventional research strategies. Because of the inaccessibility of the nervous system, one of the proposed alternatives is the study of biochemical signals in peripheral tissues which can easily and ethically be obtained in humans, and which could represent surrogate indicators of equivalent parameters in the nervous tissue. Considerable scientific support to this approach is provided by the results of recent investigations in major areas of pharmacology and psychobiology. Studies examining parameters of neurotransmission and second messenger systems in peripheral blood cells, and variations in the peripheral body fluid content of endogenous substances reflecting nervous tissue dysfunction or damage are presented in this paper as examples of efforts toward rational development and validation of novel indicators of nervous system toxicity. Cholinergic muscarinic receptors and calcium signalling in peripheral blood lymphocytes, myelin basic protein in cerebrospinal fluid, and blood polyamines are discussed as potential surrogate indicators based on the results of in vitro or in vivo animal studies of neurotoxic metals (mercury, triethyltin), pesticides (disulfoton), drugs of abuse (d-fenfluramine) and model epileptogenic compounds (kainic acid). Data from investigations examining serum prolactin, type B monoamine oxidase (MAO-B) and dopamine beta-hydroxylase (DBH) in workers occupationally exposed to manganese, lead or styrene are also presented. Although research in this field is still at its very early stage, current evidence suggests that (i) certain neurochemical markers may be valuably used in animal studies as a complement to conventional laboratory tests to augment their sensitivity or predictivity; (ii) a mechanistic research approach is required to establish which markers offer the greatest promise for application in human biomonitoring.

REFERENCE #9

To see how similar Gulf War Syndrome is to Chronic Fatigue, click here to view a comparison of symptoms in approximately 650 Desert Storm veterans suffering from Desert Storm Illness with symptoms of CFIDS. References:
1) Shafran S. The chronic fatigue syndrome. Am J Med. 1991;90:730-739. and
2) Bell DS. Chronic fatigue syndrome update. Postgrad Med. 1994;96:73-81.

REFERENCE #10

Title: Use of modafinil in the treatment of narcolepsy: a long term follow-up study.

Author: Besset A; Chetrit M; Carlander B; Billiard M

Address: Service de neurologie B, h^opital Gui-de-Chauliac, Montpellier, France.

Source: Neurophysiol Clin, 26(1):60-6 1996

Abstract: One hundred and forty patients (104 male and 36 female) aged 42.26 +/- 19.19 (range = 8 to 79.5 years) with narcolepsy-cataplexy were given modafinil (200 to 400 mg) at the Montpellier sleep disorders center from 1984 onwards. The follow-up focused on the reduction of excessive daytime somnolence (EDS), side effects and duration of treatment. In order to determine if any clinical aspect of narcolepsy could be involved in modafinil discontinuation, patients were divided into two groups according to continued or interrupted treatment. When modafinil effect on EDS was evaluated according to a scale varying from 0 (no effect) to 3 (excellent effect), 64.1% of the subjects, scored good or excellent. The mean duration of treatment was 22.05 months +/- 24.9, ranging from 1 to 114 months. Dependency signs were never observed.
Unique Identifier: 96242696

Publication Type: CLINICAL TRIAL; JOURNAL ARTICLE
ISSN: 0987-7053
Country of Publication: NETHERLANDS
CAS Registry Number: 0 (Benzhydryl Compounds); 0 (Central Nervous System Stimulants); 68693-11-8 (modafinil)

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