Fw: [paracelsus] CHRONIC FATIGUE SYNDROME AMONG PHYSICIANS

[Guest guest]

This is a really interesting article, long, but great to see that it IS being

looked into!!!!!

Take heart guys!

Scheduled to appear in " Medical Crossfire "

>

> Pre-published with permission of Editor

>

> CHRONIC FATIGUE SYNDROME AMONG PHYSICIANS:

> A POTENTIAL RESULT OF OCCUPATIONAL

> EXPOSURE TO STEALTH VIRUSES

>

>

> W. , M.D., Ph.D.

> Center for Complex Infectious Diseases

> Rosemead, CA 91770

>

> Subtitle: CFS In Physicians

>

> Address for Correspondence:

>

> CCID

> 3328 s Avenue

> Rosemead, CA 91770

> Phone:

> Fax:

> E-mail: ccidlab@...

>

>

>

> Abstract

>

> Four physicians with complex chronic disabling illnesses labeled as chronic

> fatigue syndrome (CFS) were shown by culture to be stealth virus infected.

> The clinical histories indicate multi-system stealth virus infection with

> encephalopathy (MSVIE). The exposure of physicians and other health care

> providers to stealth viruses is a potential occupational hazard.

>

> Introduction

>

> Complex arrays of symptoms typify a number of common, chronic, disabling

> illnesses. To varying extents many patients report and/or demonstrate: i)

> Impaired mental capacities, including loss of short term memory,

> difficulties in verbal expression and/or comprehension, attention deficit

> and lethargy; ii) altered personality, including a reduced capacity to

> relate emotionally to others; iii) mood changes, including depression,

> anxiety and anger; iv) sleep disturbance; v) instability of autonomic

> nervous system regulation of blood pressure, pulse rate and/or bowel

> functions; vi)headaches and; vii) generalized body aches and pains. The

> medical community is split between those who view these symptoms as an

> indication of an underlying organic disease process, and those who consider

> the symptoms merely as an extension of the normal stresses and strains of

> everyday living (1,2). Clinicians who advocate organic disease have used

> various diagnostic terms such as chronic fatigue syndrome (CFS),

> fibromyalgia, depression, Gulf war syndrome, irritable bowel syndrome,

> attention deficit, multiple chemical sensitivity, etc.; without clear-cut

> distinguishing clinical or laboratory criteria. The use of imprecise

> clinical labels has helped bolster those who believe that none of the

> illnesses constitute serious medicine.

> Public Health authorities have also been slow in pursuing a possible

> infectious etiology of CFS and related conditions. Reports of community

> outbreaks of CFS-like illnesses have typically been discredited as

> emotional over-reactions of those affected, fueled by over-zealous,

> incompetent physicians (3). With little support from established medicine,

> patients have generally had to fend for themselves in explaining their

> illness to family, friends and disability insurance carriers.

>

> For several years, I have been culturing atypical cytopathic viruses from

> CFS patients (4-6). I coined the term " stealth " because the viruses were

> apparently unseen by the cellular immune defenses responsible for

> triggering an anti-viral inflammatory response. I postulated that

> stealth-adaptation involved the deletion of critical viral genes that coded

> the major antigens targeted by T lymphocytes (4). DNA sequencing data

> obtained on an African green monkey simian cytomegalovirus (SCMV)-derived

> stealth virus support this hypothesis (7).

>

> During the course of studies on stealth-adapted viruses, numerous

> physicians have requested personal testing because of their own symptoms.

> Four particularly severe cases have been selected to help underscore the

> apparent occupational infectivity of stealth viruses.

>

> Methods

>

> Stealth Virus Cultures: Mononuclear cells were isolated from blood

> collected in acid-citrate-dextrose (ACD), yellow-topped tubes, using

> ficoll-paque (Pharmacia, NJ). The cells were added to MRC-5 fibroblasts and

> to rhesus monkey kidney cells (BioWhittaker, MD). The inoculated cultures

> were observed for the development over one to several days, of rounded

> vacuolated cells that form syncytia (4). The cytopathic effect (CPE) was

> enhanced by regularly replacing the medium (X-Vivo-15, BioWhittaker, MD).

> Confirmation of the CPE can, if required, be generally obtained by positive

> immunostaining of the culture with broadly reactive polyclonal antisera

> raised against various human herpesviruses. Immunostaining will generally

> also occur with the patient's own plasma and with many normal human sera

> (4). The CPE is morphologically distinguishable from that typically caused

> by human cytomegolovirus, human herpesvirus-6, adenovirus and

> enteroviruses. Additional distinctions from these conventional viruses can

> be made by using highly specific monoclonal typing antibodies, and by

> sequencing of polymerase chain reaction (PCR) products generated using

> various primer sets under low stringency conditions (4,6).

>

> Case Histories

>

> Case 1: An internist, who is now age 44, was well until 1987. At that time

> a nurse accidentally struck her in the hand with the needle of a syringe

> containing blood collected from an elderly patient. The patient had

> developed a transient acute encephalitis-like illness shortly after

> receiving a blood transfusion and subsequently became demented requiring

> nursing home care. The physician began developing symptoms within several

> days of the needle stick. These included vomiting, stiff neck, vertigo,

> headache, left eye pain, photosensitivity, somnolence and periodic fever to

> 100oC. CT and MRI scans were read as normal. The acute symptoms peaked at

> approximately two weeks and gradually improved. By two months, the patient

> had regained her usual alertness and, in spite of continuing vertigo,

> photophobia and headaches, she returned to work. Gradually over the ensuing

> year, she became progressively more clumsy and even occasionally fell onto

> patients being examined. She had difficulty reading because of down-beating

> nystagmus. A repeat MRI was again negative. Routine viral cultures on a

> cerebrospinal fluid (CSF) sample were negative. Detailed auditory and

> vestibular testing were consistent with endolymphatic hydrops with

> perilymphatic fistula, worse on the left side, and benign paroxysmal

> positional nystagmus, worse on the right side. The physician was unable to

> continue working. Her overall clinical condition has further deteriorated

> over the last ten years. Daily attacks of vertigo, ataxia, headaches,

> photophobia; and week-long attacks of severe fatigue; have prevented her

> from resuming any type of work. Her short term memory also became impaired.

> She has experienced frequent upper respiratory tract infections, which,

> based on positive serologies, have been labeled as Legionnaire's disease,

> Mycoplasma pneumoniae and Chlamydia pneumoniae. Among her many illnesses,

> she has had recurrent bouts of nausea, abdominal pain and diarrhea; one

> episode being attributed to C. difficile infection. Her thyroid had

> periodically become swollen and painful, with signs of de Quervain's

> thyroiditis with thyrotoxicosis associated with thyroid stimulating

> immunoglobulin. Resolution has required from 6 months to 2 years of

> prednisone therapy. She has had attacks of pancreatitis, interstitial

> cystitis, and is allergic to many foods and medications. The C5-C6 cervical

> disc has herniated, as has the L4-L5 lumbar disc. She has a reduced blood

> volume with orthostatic hypotension.

>

> Additional laboratory testing has included positive PCR for chlanydia and

> for mycoplasma, and positive serology for Borna virus. Her blood has shown

> cryoglobulins and increased fibrinogen split products with signs of

> platelet activation. Both CD4 and CD8 T lymphocyte levels have been

> reduced. Blood 2-5A' synthetase, RNase-L, alpha interferon and

> interleukin-10 levels were raised. Urinary and stool porphyins were

> elevated. Her urine also showed excess mercapturic acid, D-glucaric acid,

> B-alanine, and hydroxyproline. A stealth virus culture was strongly

> positive

>

> Brain imaging showed a 4mm herniation of the cerebellar tonsils, mild

> cerebral atrophy and discernable subcortical encephalomalacia. Reduced

> perfusion and metabolic activities involving the frontal, temporal and

> parietal lobes, were shown using SPECT and PET scans, respectively.

>

> Several years ago, the patient acquired a pet dog. The dog has had a

> remarkable medical history, including partial complex seizures, elevated

> liver enzymes, hypothyroidism, and recurrent prostate, urinary,

> gastrointestinal and eye infections. The dog also tested positive for

> stealth virus.

>

> Case 2: At 43 years of age, a previously healthy ophthalmologist

> experienced acute flu-like symptoms, which included sore throat, swollen

> cervical lymph nodes, night sweats, muscle aches and fatigue. The symptoms

> were gradually resolving when he began to develop burning parenthesia

> involving different regions of his body. These were accompanied by marked

> muscle weakness. Palpable nerves were tender. He had to discontinue work

> for two months. When he returned, he was still bothered by paresthesia,

> weakness, insomnia and fatigue. A further exacerbation occurred eight

> months later with several days of confusion and disorientation, followed by

> apparent reduction in short-term memory, attention span, and verbal

> expression and comprehension. Muscle fasciculation was also noted. He again

> discontinued work and has remained disabled for the last 11 years. During

> this time he has periodically developed superficial, mucus exudative

> lesions that involve areas within the nostrils and on the lips. Cognitive

> impairments were documented on neuropsychological testing. Hypoperfusion

> was seen on SPECT scan and hypometabolism was seen on PET scan. Abnormal

> routine laboratory testing has included slightly elevated liver function

> tests. Special tests have shown marked elevations in alpha interferon and

> in interleukin 1. Material collected from the exudative lesions has shown

> herpesviral like-particles on electron microscopy. Viruses were also seen

> in a semen preparation and in an ultracentrifuge pellet from an aceellular

> CSF sample. Multiple stealth virus cultures from blood, CSF, lip lesion,

> and semen, have been consistently positive on multiple occasions between

> 1992 and 1998.

>

> Case 3: In 1983, a 38-year old medical oncologist was exposed to

> hematemesis and bloody diarrhea from an elderly patient with persistent

> thrombocytopenia, splenomegaly and progressive cirrhotic liver disease. The

> patient showed elevated liver enzymes, but remarkably normal bilirubin

> until shortly before her death. Among other investigations, the elderly

> patient was negative for hepatitis A and B by serology, and strongly

> positive for anti-EBV viral capsid antigen (VCA). Within two months of this

> patient's death, the attending physician began to experience irritable

> bowel symptoms with abdominal discomfort and episodes of diarrhea. He also

> tested strongly positive for EBV VCA, (titer 1:5,000). His symptoms

> gradually extended to include diffuse myalgia and anthralgia, severe and

> progressive lethargy, and reduced exercise tolerance. Additionally, the

> physician began to experience headaches accompanied by blurring of vision

> and occasional diplopia, night sweats, periodic palpitations and insomnia.

> He became intolerant of bright light, which would trigger headaches, and

> was also intolerant of cold night air that would trigger muscle aches and

> anthralgia. He also had intermittent bouts of pharyngitis. The illness

> continued to progress with increasing generalized muscle weakness, chest

> pains, shortness of breath, mild ataxia and tremor. He was seen by numerous

> specialists whose aggregate diagnoses included the following: i) Labile

> hypertension progressing to fixed hypertension associated with left

> ventricular hypertrophy and EKG signs of viral cardiomyopathy. ii)

> Hepato-splenomegaly with fluctuating elevated liver enzymes and steatosis

> on liver biopsy, now progressing to cirrhosis. iii) Progressive cerebral

> atrophy with hypoperfusion and hypometabolism, manifesting as personality

> disorder, impaired memory, depression and early dementia. He has difficulty

> following conversations and is easily confused. iv) Endolymphatic hydrops.

> v) Prolonged episodes of moderate thrombocytopenia with ecchymosis,

> telangiectasia and splinter hemorrhages. Plasmacytosis was seen on bone

> marrow biopsy with ohgoclonal rearrangements within both B and T

> lymphocytes. Megaloblastic anemia, refractory to folic acid and vitamin B12

> therapy. vi) Multiple chemical sensitivity and multiple food allergies,

> which induce nausea and headaches. vii) Localized psoriasis and; viii)

> Recent onset of type II diabetes. He has been on disability since 1984.

>

> Abnormal laboratory tests include elevated levels of alpha interferon,

> interleukin 1, tumor necrosis factor and C reactive protein. He has

> auto-antibodies to nuclear, nucleolar and cytoplasmic antigens. 1gA and 1gG

> levels are below normal, as are qualitative and quantitative NK cell

> assays. CD4/CD8 T lymphocyte ratio is elevated. Plasma amino acid levels

> are reduced, whereas plasma ammonia is increased. Stealth virus cultures

> have been repeatedly positive since 1991.

>

> Case 4: A 55 year old financially successful physician was alerted to a

> possible illness when he noticed difficulties switching his concentration

> from counting a patient's pulse to watching the clock. He also began to

> forget telephone numbers. He had to carefully position himself before

> getting up from a stool so as not to stagger and appear drunk. He stopped

> practicing medicine when he found himself waiting for another motorist to

> come to a traffic light so as to remind him on which color light he could

> proceed. Neurological examinations were conducted, but no abnormalities

> were found. His colleagues reassured him that it was nothing other than

> stress. He became despondent and overweight. His marriage failed and his

> adult children sided with their mother in the disposition of various

> assets. For the next 10 years, the physician lived alone, unable to drive

> at night because of disorientation; unable to socialize because of verbal

> and cognitive problems; and unable to obtain relief in spite of literary

> having a pharmacy within his apartment. A formal neurological examination

> was arranged in 1994, to help document his disability for a Public health

> report. It was essentially unremarkable except for a 4/5 mild bilateral

> weakness in hand gripping. The examining neurologist admitted that he was

> considering schizophrenia when the patient began referring to " multiple

> little men in my brain not listening to each other. " The disabled physician

> was provided a trip to Hawaii but only on four occasions throughout a whole

> month did he leave his hotel room. His travelling companion commented on

> his relentless suffering and inability to take delight from any of the

> days' happenings. When not sleeping, he would struggle with expressing his

> ideas and would invariably return to the theme of his illness. Upon his

> return to California, he answered a mail-order bride advertisement from the

> Philippines, where he now resides. Blood and an otherwise normal CSF sample

> were strikingly positive in stealth viral cultures.

>

> Discussion

>

>

> In spite of the obvious differences, complexities and severity of the

> illnesses experienced by these four physicians, they are all currently

> diagnosed as having CFS. In current medical practice, this term embraces a

> broad range of illnesses without defined boundaries at either the mild or

> severe extremes. It lumps seriously ill patients, such as those described

> in this paper, with the so called " worried well " who are accused of over

> utilizing medical services (8). For sick patients, the CFS label is not

> infrequently applied to individuals with variably recurring multi-system

> illnesses with an overlay of neuropsychiatric symptomatology. A CFS

> diagnosis will often limit the medical quest to determine the actual causes

> of the many and varied symptoms experienced by the patient. Being

> physicians, the patients described in this paper, have had access to more

> extensive laboratory and ancillary testing than do most CFS patients. In

> particular, they sought and tested positive for stealth viral infections.

>

> Stealth viruses refer to a molecularly heterogeneous grouping of atypically

> structured viruses that induce a vacuolating cytopathic effect (CPE) in

> culture, yet seemingly are unable to evoke an anti-viral inflammatory

> response in vivo (4-7). Sequence studies on an African green monkey simian

> cytomegalovirus-derived stealth virus are consistent with the deletion of

> genes coding for the major targets for anti-CMV cytotoxic T lymphocytes

> (CTL) mediated immunity (6). More impressively, portions of this virus have

> gained many additional sequences of both cellular (9) and bacterial origins

> (10). The SCMV and captured cellular and bacterial sequences have undergo

> considerable mutations, yielding a diverse range of molecular and antigenic

> components. Stealth adaptation can presumably occur with other cytopathic

> viruses of human and animal origin. The lack of an accompanying

> inflammatory reaction and poor growth in routine viral cultures have helped

> these viruses go unnoticed by clinical investigators.

>

> The molecular and antigenic diversity of stealth viruses can help explain

> the sometimes baffling results of PCR and serological based assays obtained

> in CFS patients. In Case 1, for example, positive results were obtained in

> tests for Borna virus, Legionella, chlamydia and mycoplasma. Although it is

> conceivable that the patient had all of these infections, it is more likely

> that the results reflect molecular and antigenic cross-reactivity. The

> presence of stealth viruses, especially their capacity to assimilate genes

> of bacterial origins, poses a caveat on the interpretation of many

> currently used PCR and serological based tests.

>

> While the encephalopathic manifestations tend to dominate the clinical

> features of most CFS patients, as is amply revealed in the case histories,

> many other organ systems are affected. The detection of various

> abnormalities often reflects the extent to which laboratory and ancillary

> diagnostic services are employed. The sensitivity and specificity for CFS

> of many of the various tests are not established. Given the vagueness of

> the clinical diagnosis, it would not be surprising if major discrepancies

> occurred. The diversity of laboratory results is, however, quite consistent

> with an overall diagnosis of multi-system stealth virus infection with

> encephalopathy (MSVIE). This term can embrace the widespread illnesses,

> including signs of autoimmunity, allergy and metabolic failures, that were

> especially apparent in cases 1 and 3.

>

> The four physicians have experienced many of the problems faced by CFS

> patients. The social toil has included loss of income with considerable

> medical expenses incurred in the performance of laboratory tests and

> ancillary investigations. Two of the patients were divorced largely due to

> personality changes and loss of empathy with their spouses. One physician

> lived apart from his wife for several years in fear of transmitting his

> infection. Electron microscopy and stealth virus testing of semen was a

> hopeful gesture that they might still be able to conceive a healthy child.

> The diagnosis of CFS was used in the denial of the first physician's appeal

> for Worker's Compensation, even though her initial illness clearly followed

> a needle stick injury. Another physician felt pressured to reach a

> settlement with his long term disability carrier who had decided to

> terminate his benefits.

>

> One of the physicians visited NIH investigators, and met with CDC officials

> trying to alert them to his illness without success. Patient 4 was formally

> reported to a County Health Department in 1994, again with no response. The

> reluctance of Public Health authorities to deal with chronic disabling

> illnesses may be partially explained by an inadequacy of conventional

> epidemiological tools when applied to complex and varied infectious

> diseases. The sequence data on the prototype stealth virus may also bear on

> Public Health concerns regarding the wisdom of having used African green

> monkeys to produce live poliovirus vaccine.

>

> Although only four cases are presented, many more physicians have sought

> stealth virus testing. Several other physicians have begun anti-viral

> therapy with ganciclovir with self-reported benefit. Courageous clinicians

> have continued to treat CFS patients, but with a greater respect for the

> potential contagiousness of the illnesses they are encountering.

>

> References

>

> 1.. Goldstein JA. Chronic Fatigue Syndromes: The Limbic Hypothesis.

> New York. Haworth; 1993

> 2.. Barsky AJ, Borus JF. Functional somatic syndromes. Ann Int Med.

> 1999;130:910-21

> 3.. Shefer A, Dobbins JG, Fukuda K, et al. Fatiguing illness among

> employees in three large state office buildings, California, 1993: was

> there an outbreak? J Psychiatr Res 1997;31:31-43

> 4.. WJ, Zeng LC, Ahmed K, Roy M. Cytomegalovirus-related

> sequences in an atypical cytopathic virus repeatedly isolated from a

> patient with the chronic fatigue syndrome. Am J Path. 1994;145:441-452.

> 5.. WJ. Severe stealth virus encephalopathy following

> chronic fatigue syndrome-like illness: Clinical and histopathological

> features. Pathobiology 1996;64:1-8.

> 6.. WJ. Stealth adaptation of an African green monkey simian

> cytomegalovirus. Exp Mol Path. 1999;66:3-7.

> 7.. WJ. Detection of RNA sequences in cultures of a stealth

> virus isolated from the cerebrospinal fluid of a health care worker with

> chronic fatigue syndrome. Pathobiology 1997;65:57-60.

> 8.. Bowers L. Community psychiatric nurse caseloads and the

> 'worried well': misspent time vital work? J Adv Nurs. 1997 26:930-6.

> 9.. WJ. Cellular sequences in stealth viruses. Pathobiology

> 1998;66:53-58.

> 10.. 10. WJ. Bacteria related sequences in a simian

> cytomegalovirus-derived stealth virus

>

>

>

~*Meredith*~