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From the Townsend Letter
October 2006

 

Recent Progress in Clinical Applications
and Research in Fibromyalgia

by Robert W. Bradford, Professor of Medicine, D. Sc. NMD, and Henry W. Allen, Director of Clinical Biochemistry, BRI


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FUNGUS IN DISEASES OTHER THAN FIBROMYALGIA

Fungus in Cancer
Of 20 cancer patients who were given Amphotericin B therapy, 40% died of fungal infection and 20% from underlying disease with fungal infection. Even though the diagnosis was made and antifungal therapy begun before death in 75% of the cases, invasive fungal infection had a 60% overall mortality in these patients.

A new treatment for fibromyalgia, proven highly successful in the Ingles Integrative Hospital Mexico, is the use of an Alkanylated Sulfur Compound administered intravenously. All patients treated have responded dramatically after one or more treatment protocols.59 See Chart 11.

Candida lusitaniae fungemia was detected in 12 cancer patients at the M.D. Anderson Cancer Center (Houston, Texas) from 1988 to 1999. Four of these patients had a solid tumor, while the remaining eight were diagnosed with leukemia. The mortality rate associated with C. lusitaniae infection was 25%.87

In a surveillance study of candidiasis in cancer patients, conducted by the Invasive Fungal Infection Group of the European Organization for Research and Treatment of Cancer, 249 cases were studied. Candida albicans was isolated in 70% of the 90 cases involving patients with solid tumors and in 36% of those diagnosed with leukemia. Candida glabrata was associated with the highest mortality rate (odds ratio, 2.66:1).88

In another study of patients having solid tumors of the respiratory tract, colonization by fungi and/or yeasts was frequently found.89

Scedosporium prolificans infection was analyzed in 18 patients from whom the fungus was isolated during the period 1990 to 1999. Six of these patients had confirmed disseminated infection; four patients had leukemia; and one patient had breast cancer.90
At the Sloan-Kettering Cancer Center, New York, 22 isolates of Candida dubliniensis were recovered from 16 patients with solid-organ or hematologic (leukemic) malignancies, including those having AIDS. Two patients with cancer had invasive infections.91

The clinical charts of cancer patients with documented fungal infections in a children's hospital in Italy from 1980 to 1990 were reviewed. Of 37 patients, ranging in age from three months to 18 years, 21 patients were treated for leukemia while 17 had solid tumors. In 40% of the cases, the fungal infection developed as primary infection, not preceded by any other infectious episode. Fungemias without evident organ localization accounted for 40% of the cases with a mortality rate of 20%. The other 22 cases (60%), nine of whom (41%) died, were classified as invasive mycoses. Mortality was highest among patients with fungal infection (72%), compared to those with only Candida yeast infections (28%) Note: Yeast is fungus.92

Aspergillus terreus developed in a patient with acute lymphoblastic leukemia following chemotherapy. A. terreus is one of the invasive Aspergillus species.93

Systemic infections related to fluconazole-resistant fungus (yeast) are increasingly observed in immunocompromised patients receiving fluconazole as an antifungal treatment. A single case of invasive candidiasis was caused by Candida ciferrii in a patient with acute myeloid leukemia. Until now, C. ciferrii has not been known to cause invasive fungal infections in humans.94

Fusarium species are fungi that attack most grains, including corn, wheat, rice, barley, and others in the field before harvest. A single case of disseminated fungal infection caused by Fusarium was reported in an immunosuppressed patient suffering from acute lymphobastic leukemia. This report and a review of recent literature suggests that Fusarium species are emerging fungal pathogens in immunosuppressed patients.95

In a second report, Fusarium moniliforme was isolated from blood culture of a six-month-old infant who had infantile leukemia and whose family raised livestock.96

Fungus in Arthritis
The following are case reports of patients suffering from some form of arthritis and fungal infection. The first case is concerned with arthritis due to Candida glabrata in two different joints at different times in the same patient. The first episode of arthritis was in the right ankle and lasted more than a year before the patient agreed to the proposed treatment. The intravenous therapy with antibiotics failed, but was followed by weekly intra-articular administration of amphotericin B for more than 20 weeks, combined with oral itraconazole. Several weeks later, the patient developed arthritis in the left knee while still being treated by itraconazole. Intravenous amphotericin B therapy begun immediately was successful.97

Cryptococcus neoformans infection generally is rare, particularly in the hand. Another report describes the case of a 50-year-old patient with C. neoformans infection in his hand. 98

A case of arthritis from coccidioidomycosis in a 62-year-old man is described. The diagnosis was made by fine-needle aspiration and confirmed by positive cultures and antigen testing. Coccidioidomycosis can infect bones and joints, especially the knee which was the site of infection in this case. 99

In another case, a patient developed osteoarthritis of an ankle, due to infection by Neocosmospora vasinfecta (Ascomycete group of fungi) caused by accidental multiple trauma to his legs while in Africa. Parenteral antifungal therapy failed, and amputation was required.100

A case of arthritis of the right wrist caused by Aspergillus fumigatus without evidence of a generalized infection is described, following chemotherapy for acute lymphoblastic leukemia. The diagnosis was made by surgical biopsy. Oral itraconazole was given, and the arthritis improved.101 Another report describes a patient with polyarthritis (four separate sites) occurring over a period of several years caused by Candida lambica, probably acquired from a contaminated wound. C. lambica has not been previously reported to cause infectious arthritis. Chronic alcoholism was the only apparent risk factor for dissemination.102

Prostaglandin Production by Pathogenic Fungi
The pathogenic fungi Cryptococcus neoformans and Candida albicans produce prostaglandins that have been demonstrated. Prostaglandins isolated from both these fungi and synthetic PGE2 display the same biological activities towards fungal and mammalian cells, implying that the fungi are producing PGE2. One of these activities is the conversion of the yeast (bud) form of the fungus to the hypha (thread) form. This prostaglandin, applied to mammalian cells, down-modulates tumor necrosis factor (TNF) production while also up-regulating interleukin-10 (IL-10) production. PGE2 is shown to be critical for fungal growth and can modulate host immune functions. This discovery reveals a virulence mechanism that has potentially great implications for understanding the mechanisms of chronic fungal infections in humans.103 IL-10 has been found to be associated with the down-regulation of T-cell helper cells.119

Pulmonary Aspergillosis in AIDS Patients
Symptomatic pulmonary aspergillosis rarely has been reported in AIDS patients. This report describes 13 patients with pulmonary aspergillosis detected an average of 25 months after the diagnosis of AIDS, usually following corticosteroid use or the use of broad-spectrum antibiotics. Two major patterns of disease were observed: invasive aspergillosis (ten patients) and obstructing bronchial aspergillosis (three patients).

Dissemination to other organs occurred in at least two patients, and direct invasion of extrapulmonary sites was seen in two others. It was concluded that pulmonary aspergillosis is a possible late complication of AIDS.104

Mucor Cerebral Aneurysm Rupture
A 63-year-old female was admitted to the hospital with disturbed consciousness and high fever. Her past history was that of diabetes mellitus, liver cirrhosis, and nasal sinusitis. Intravenous cefotaxime and ampicillin therapy was immediately begun. The patient began to improve, but on the sixth hospital day, she went into a coma and died on the ninth day. An autopsy revealed Mucor at the site of the aneurysm rupture.105

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