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M.E. (and ICD-CFS) Articles, Research and Books 
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Research topics: General Articles and Research Overviews, Immune System Research, Viral Research, Cardiac Research, Exercise Research, Muscle Research, Metabolic Research, Neurological and Cognitive Research, Genetic Research, Neuroendocrine Research, and Miscellaneous Research.
Article topics: The Definitions of M.E., On 'fatigue', CBT, GET and the unscientific 'behavioural' paradigm of M.E., On 'stress', M.E. Outbreaks, On the Name Myalgic Encephalomyelitis, M.E. and Other Illnesses, Children with M.E., The Severity of M.E., M.E. Fatalities, Activism Articles, Articles sorted by Author, Articles sorted by Country and Historical, Political and Medical Overviews.
Topic on this page: Enteroviral and Post Polio Syndrome Research, HHV6 Research, Stealth Virus Research, General Viral Research and Relevant Books - page 2 of 5
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Enteroviral and Post-polio Research - continued
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Chronic enterovirus infection in patients with postviral fatigue syndrome. Yousef GE, Bell EJ, Mann GF, Murugesan V, Smith DG, McCartney RA, Mowbray JF. Lancet. 1988. Department of Pathology, St Mary's Hospital Medical School, London.
76 patients with the postviral fatigue syndrome (PVFS) and 30 matched controls were investigated. Virus isolation was attempted from concentrated faecal samples by direct culture and after acid dissociation of virus from antibody. Positive cultures of enteroviruses were obtained from 17 (22%) patients and 2 (7%) controls. An enterovirus-group-specific monoclonal antibody, 5-D8/1, directed against the VP1 polypeptide, was used to detect enteroviral antigen in the circulation, either free or complexed with antibody. VP1 antigen was detected in the serum of 44 (51%) of a further group of 87 PVFS patients. The number of patients positive for VP1 antigen was greater (42/44) when IgM complexes were detectable than when they were not (2/23). 1 year later, the 17 patients of the first group of 76 with positive cultures were again studied. The same virus was again isolated from 5 (29%), 13 (76%) had detectable IgM responses to enteroviruses, and 9 (53%) were positive for VP1 antigen in the serum. These results show that chronic infection with enteroviruses occurs in many PVFS patients and that detection of enterovirus antigen in the serum is a sensitive and satisfactory method for investigating infection in these patients.
Myalgic Encephalomyelitis - a persistent enteroviral infection? Dowsett E, Ramsay AM, McCartney RA and Bell EJ. Postgraduate Medical Journal 1990; 66: 526-530.
Abstract: Myalgic encephalomyelitis is a common disability but frequently misinterpreted. Amongst 6,000 patients referred for general microbiological diagnosis between 1975 and 1987, 420 cases were recognized. Coxsackie B neutralization tests, in 205 of these, demonstrated significant titres in 103/205 (50%), while of 124 additionally investigated for enteroviral IgM, 38/124 (31%) were positive. This illness is distinguished from a variety of other post-viral states by an unique clinical and epidemiological pattern characteristic of enteroviral infection. Prompt recognition and advice to avoid over-exertion is mandatory. Routine diagnosis, specific therapy and prevention, await further technical advances.
Post viral fatigue syndrome: persistence of enteroviral RNA in skeletal muscle and elevated creatine kinase. Archard LC, Bowles NE, Behan PO, Bell EJ, Doyle D. Journal of the Royal Society of Medicine 1988; 81: 326-9.
Abstract: Enterovirus-specific probes have been prepared by reverse transcription of conserved sequences in purified Coxsackie B2 virus genomic RNA and molecular cloning techniques. These probes were used in quantitative slot blot hybridizations to test for the presence of enterovirus-specific RNA in skeletal muscle biopsy specimens from 96 patients who had suffered from the postviral fatigue syndrome myalgic encephalomyelitis for up to 20 years. Biopsy specimens from 20 patients were positive for the presence of virus-specific RNA with hybridization signals more than three standard deviations greater than the mean of the normal muscle controls. Biopsies from the remaining 76 patients were indistinguishable from the controls. These data show that enterovirus RNA is present in skeletal muscle of some patients with postviral fatigue syndrome up to 20 years after onset of disease and suggest that a persistent virus infection has an aetiological role.
Evidence for persistent enterovirus infection of the central nervous system in patients with previous paralytic poliomyelitis. Muir P, Nicholson F, Sharief MK, Thompson EJ, Cairns NJ, Lantos P, Spencer GT, Kaminski HJ, Banatvala JE. Department of Virology, UMDS St. Thomas' Hospital, London, United Kingdom.
It has been suggested that late onset neurological deterioration after poliomyelitis may be due in some cases to persistent poliovirus infection of the central nervous system. In view of this, we decide to determine whether polioviruses and other enteroviruses can persist in the central nervous system. In a previous study, one of us (M.K.S.) reported serological evidence of persistent poliovirus infection of the central nervous system (CNS) in a proportion of these patients. We have now studied cerebrospinal fluid (CSF) from these patients for the presence of enterovirus RNA sequences using the polymerase chain reaction (PCR). Enteroviral RNA was detected in 3 of 24 patients with a clinical diagnosis of post-polio syndrome, but in none of 36 patients with stable poliomyelitis, and none of 36 patients with other neurological conditions of noninfective origin. All 3 patients in whom viral RNA was detected had high intrathecal levels of poliovirus-specific oligoclonal IgM bands. In a second study we examined formalin-fixed postmortem CNS tissue from 7 patients with a history of paralytic poliomyelitis. Enterovirus RNA was detected in tissue from the spinal cord from 3 patients, but not in the cerebral cortex. We are now conducting a larger prospective, blind study of patients with evidence of late deterioration. Analysis of the first 30 patients studied revealed the presence of enterovirus RNA in CSF of 1 of 4 patients with unexplained late-onset post-polio weakness, 1 of 6 with some evidence of clinical deterioration, but none of 20 without inexplicable signs of post-polio weakness. Enteroviral RNA was also detected in spinal cord from 2 of 3 patients who died from other causes during this study. These studies provide virological evidence that enteroviruses may persist in the CNS of man. Further study is required in order to understand fully the biological and clinical significance of these findings.
[Enterovirus infections in new disguise] [Article in Swedish] Fohlman J, Friman G, Tuvemo T. Infektionskliniken, Akademiska sjukhuset, Uppsala.
Enteroviruses (Coxsackie A and B, echovirus, poliovirus) belong to a group of small RNA-viruses, picomavirus, which are widespread in nature. Enteroviruses cause a number of wellknown diseases and symptoms in humans, from subclinical infections and the common cold to poliomyelitis with paralysis. The development of polio vaccines is the greatest accomplishment within the field of enterovirus research and the background work was awarded the Nobel prize in 1954. New knowledge implies that enteroviruses play a more important part in the morbidity panorama than was previously thought. Chronic (persistent) enteroviruses were formerly unknown. Serologic and molecular biology techniques have now demonstrated that enteroviral genomes, in certain situations, persist after the primary infection (which is often silent). Persistent enteroviral infection or recurrent infections and/or virus-stimulated autoimmunity might contribute to the development of diseases with hitherto unexplained pathogenesis, such as post polio syndrome, dilated cardiomyopathy, juvenile (type 1) diabetes and possibly some cases of chronic fatigue syndrome.
Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy. Bowles NE, Bayston TA, Zhang HY, Doyle D, Lane RJ, Cunningham L, Archard LC. The Journal of Medicine 1993; 24(2-3): 145-60.
Abstract: Molecular hybridization using an enterovirus group specific probe detected virus RNA in muscle biopsy samples from 25 of 96 cases of inflammatory muscle disease and similarly from 41 of 158 cases of postviral fatigue syndrome (PFS). Enterovirus RNA was detected in only two of 152 samples of control muscle. The inflammatory myopathy group comprised patients with polymyositis (PM), juvenile dermatomyositis (JDM) or adult dermatomyositis (DM), and all showed the presence of an inflammatory infiltrate and fiber necrosis on histological examination of a muscle biopsy sample. In contrast, muscle samples from the PFS group were histologically normal except for non-specific changes such as occasional single fiber atrophy. By analogy with enteroviral myocarditis, which can progress to a post-inflammatory disease with persistence of virus in myocardium and disposes to the rapid development of dilated cardiomyopathy, we propose that PFS syndrome may be a sequela of a previous inflammatory viral myopathy.
Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA. Cunningham L, Bowles NE, Lane RJ, Dubowitz V, Archard LC. Journal of General Virology 1990; 71 (6): 1399-402.
Abstract: A subgenomic restriction fragment from cDNA prepared from Coxsackie B2 virus (CVB2) RNA was subcloned into a riboprobe vector allowing the production of enteroviral group-specific RNA probes complementary to either the positive (genomic) or negative (template) strand of enteroviral RNA. These riboprobes were used to follow productive infection of cultured cells by CVB2; as expected, positive strand RNA was synthesized in approximately 100-fold excess over negative strand. RNA was extracted from muscle biopsy samples from patients with chronic fatigue syndrome and probed for the presence of enteroviral RNA. In cases where enteroviral RNA was detected the amounts of positive and negative strands of enteroviral RNA were approximately equal, in contrast to the situation in lytic infection of cultured cells. This suggests that enterovirus persistence in muscle is due to a defect in control of viral RNA synthesis.
Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA. Cunningham L, Bowles NE, Lane RJ, Dubowitz V, Archard LC. Department of Biochemistry, Charing Cross and Westminster Medical School, London, U.K.
A subgenomic restriction fragment from cDNA prepared from Coxsackie B2 virus (CVB2) RNA was subcloned into a riboprobe vector allowing the production of enteroviral group-specific RNA probes complementary to either the positive (genomic) or negative (template) strand of enteroviral RNA. These riboprobes were used to follow productive infection of cultured cells by CVB2; as expected, positive strand RNA was synthesized in approximately 100-fold excess over negative strand. RNA was extracted from muscle biopsy samples from patients with chronic fatigue syndrome and probed for the presence of enteroviral RNA. In cases where enteroviral RNA was detected the amounts of positive and negative strands of enteroviral RNA were approximately equal, in contrast to the situation in lytic infection of cultured cells. This suggests that enterovirus persistence in muscle is due to a defect in control of viral RNA synthesis.
Evidence for enteroviral persistence in humans. Galbraith DN, Nairn C, Clements GB. Regional Virus Laboratory, Ruchill Hospital, Glasgow, UK.
We have sought evidence of enteroviral persistence in humans. Eight individuals with chronic fatigue syndrome (CFS) were positive for enteroviral sequences, detected by PCR in two serum samples taken at least 5 months apart. The nucleotide sequence of the 5' non-translated region (bases 174-423) was determined for each amplicon. Four individuals had virtually identical nucleotide sequences ( > 97%) in both samples. The sequence pairs also each had a unique shared pattern indicating that the virus had persisted. In one individual (HO), it was clear that there had been infection with two different enteroviruses. In the remaining three individuals, the lack of unique shared features suggested that re-infection had occurred, rather than persistence. With the exception of HO, the sequences fell into a subgroup that is related to the Coxsackie B-like viruses.
Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatine kinase. Archard LC, Bowles NE, Behan PO, Bell EJ, Doyle D. Department of Biochemistry, Charing Cross and Westminster Medical School, London.
Enterovirus-specific probes have been prepared by reverse transcription of conserved sequences in purified Coxsackie B2 virus genomic RNA and molecular cloning techniques. These probes were used in quantitative slot blot hybridizations to test for the presence of enterovirus-specific RNA in skeletal muscle biopsy specimens from 96 patients who had suffered from the postviral fatigue syndrome myalgic encephalomyelitis for up to 20 years. Biopsy specimens from 20 patients were positive for the presence of virus-specific RNA with hybridization signals more than three standard deviations greater than the mean of the normal muscle controls. Biopsies from the remaining 76 patients were indistinguishable from the controls. These data show that enterovirus RNA is present in skeletal muscle of some patients with postviral fatigue syndrome up to 20 years after onset of disease and suggest that a persistent virus infection has an aetiological role.
Coxsackie B viruses and myalgic encephalomyelitis. Bell EJ, McCartney RA, Riding MH. Journal of the Royal Society of Medicine 1988; 81: 329-31.
Abstract: Data collected over the past 6 years suggest that Coxsackie B viruses (CBV) play an important role in myalgic encephalomyelitis (ME). Since psychological upset is a feature of this illness, 247 patients, recently admitted to a psychiatric hospital, were tested for neutralizing antibodies to CBV. A total of 12.5% had significantly raised CBV titres compared with 4-5% of 'well' control groups; the percentage positive was greatest (21%) in those aged 30-39 years. During 1985 and 1986 sera from 290 adults with ME were tested using the newly developed CBV IgM ELISA test; 37% were CBV IgM positive compared with 9% of 500 'well' adult controls. Forty-seven children, with ME were similarly tested during this period; 38% were positive, implying recent or active CBV infection. The combined use of this ELISA test and the virus probe techniques now available should further help to elucidate the exact role of CBV in this disabling illness.
How enteroviruses might evade the immune system. Cunningham et al. J Gen Virology, 1990, 71, 1399
Advantages of the “polio-like” description – general awareness of the entity by physicians; information readily available in standard text books and medical journals. Supportive evidence: (a) a virological distinction between the 2 diseases was not available until the development of virus culture in 1948. This resulted in the discovery of some 69 related polio and non-polio enteroviruses. Although the majority of host/virus contacts produce subclinical infections, these agents are extremely versatile with a wide range of overlapping tissue affinities. They are reliably associated with many acute infections of the respiratory and intestinal tracts; with middle ear, neurological, skin, muscle, throat and mucous membrane infections; with epidemics of viral meningitis, Bornholm and Hand Foot and Mouth disease and with chronic sequelae affecting the brain, heart muscle, the pancreas and other endocrine glands. (b) Serological studies in Iceland, following the introduction of oral polio vaccine in 1958, indicated that a 1948 epidemic of Iceland Disease (ME) in the north of the island effectively blocked a 1957 epidemic of polio type I in the south from spreading north. At the same time the response to polio type I oral vaccine was standard in the south but aberrant in patients who suffered from the 1948 epidemic in the north. This indicated a close relationship between the agents of both diseases with competition for receptor sites in the bowel and persistence of the 1948 epidemic agent over 7 years.
Elevated Plasma Prolactin and EEG Slow Wave Power in Post-Polio Fatigue: Implications for a Dopamine Deficiency Underlying Post-Viral Fatigue Syndromes Richard L Bruno, Susan Creange, Jerald R Zimmerman and Nancy M Frick HarvestCtr@AOL.COM Journal of Chronic Fatigue Syndrome 1998 vol.4 no.2 page 61-75
To test the hypothesis that plasma prolactin and electroencephalographic (EEG) slow wave activity are correlated with fatigue, 33 polio survivors without medical or psychologic comorbidities were studied. Subjects were administered the Post-Polio Fatigue Questionnaire (PFQ) and had resting measurement of both plasma prolactin and bilateral temporal-occipital power across the EEG frequency spectrum. Typical daily fatigue severity on the PFQ was significantly correlated with daily difficulty with attention, staying awake and motivation, but not with measures of acute polio severity or the number of limbs affected by late-onset Post-Polio Sequelae symptoms. Prolactin was significantly correlated with daily fatigue severity on the PFQ (r = .39; p <0.5). EEG power was equal between the two hemispheres across all frequency bands. However, EEG slow wave power in the right hemispheres was significantly correlated with daily fatigue severity and prolactin level (r = .37; p <.05). Using multiple linear regression, age at acute polio, frequency of difficulty with attention on the PFQ, prolactin and right hemisphere slow wave power predicted 72% of the variance of the daily fatigue severity rating (r = .85; p < .0001). These data suggest that increased prolactin secretion and EEG slowing are related to the severity of post-polio fatigue, findings similar to those in patients with acute paralytic and non-paralytic poliomyelitis and with chronic fatigue syndrome. A primary role is suggested for a dopamine deficiency (versus serotonergic receptor supersensitivity) underlying impaired cortical activation and the symptoms associated with putative post-viral fatigue syndromes.
Chronic fatigue syndrome--aetiological aspects Dickinson CJ Wolfson Institute , St. Bartholomew's & Royal London School of Medicine & Dentistry, London, UK. Eur J Clin Invest 1997 Apr;27(4):257-67 (ISSN: 0014-2972)
"Regional blood flow studies by single photon-emission computerized tomography (SPECT) have been more consistent. They have revealed blood flow reductions in many regions, especially in the hind brain. Similar lesions have been reported after poliomyelitis and in multiple sclerosis--in both of which conditions chronic fatigue is characteristically present. In the well-known post-polio fatigue syndrome, lesions predominate in the RAS of the brain stem. If similar underlying lesions in the RAS can eventually be identified in CFS, the therapeutic target for CFS would be better defined than it is at present. A number of logical approaches to treatment can already be envisaged".
Thu, 15 Feb 2001 "Dr. Richard L. Bruno" CFSENG@AOL.COM
I have received some questions as a result of my recent post to Co-Cure on CFS vs PPS and OPV which I thought might be of interest to the Co-Cure readers. Question: "What, specifically, was it from Sabin's 1947 data that suggests that some of the people with ME/CFS may be survivors of nonparalytic polio? Are there research reports available online?" Answer: They are not available on line. I went through the Sabin Archive in Cincinnati. Take a look at the non-paralytic polio papers and the "Parallels" between polio and CFS paper at: http://members.aol.com/harvestctr/pps/lib2.html Question: "And what about those people who developed the disease as teenagers in the 1990s (and who weren't around in the 1950s)? If any of them have NPP, would they have contracted it from the older patients, or from vaccines, or from some other source?" Answer: They would not have had polio at all. If a virus caused their CFS, it would have been from some other source. Our best guess as a cause is another enterovirus very similar to the poliovirus, e.g., Coxsackie B4, that can cause brain and spinal cord lesions identical to those caused by the poliovirus. Polio only means gray in Latin, referring to damage to unmyelinated neurons. Poliovirus causes "polio," but so do other viruses, e.g., Enterovirus 71 causing "polio" in Brazil. Question: "Is there a way to test for NPP in today's patients?" Answer: You can do an EMG, where needles are inserted into muscles, to look for "silent" denervation. But EMG can give false negatives even in polio survivors. We have found MRI and hormonal correlates of PPS fatigue but they are identical to the findings s in CFS! Question: "Would vaccine programs in place since the 1950s have given everyone so many antibodies to polio that such testing would be futile?" Answer: Probably. By if one had a "natural" poliovirus infection their antibody titre might be higher than if they only had the vaccine. Hope this helps! Dick Bruno
Poliovirus induces an early impairment of mitochondrial function by inhibiting succinate dehydrogenase activity.Koundouris A, Kass GE, Johnson CR, Boxall A, Sanders PG, Carter MJ School of Biological Sciences, University of Surrey, Guildford, Surrey, United Kingdom. PMID: 10814509, UI: 20275463
Poliovirus infection of COS-1 and T47D cells caused a rapid decrease in total cell respiration, and this was attributed to an inhibition of mitochondrial respiration. The stimulation of mitochondrial respiration by pyruvate plus malate or succinate was impaired in saponin-permeabilised cells. However, this inhibition could be overcome by the addition of N,N,N',N'-tetramethyl-1, 4-phenylenediamine and ascorbate. The activity of succinate dehydrogenase was impaired in parallel with the inhibition of mitochondrial respiration during poliovirus infection. This shows that mitochondrial function is profoundly altered during poliovirus infection and that this occurs primarily through inhibition of electron flow at complex II of the mitochondrial respiratory chain. Copyright 2000 Academic Press.
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Viral Research - continued
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Page 3: Enteroviral and Post-polio Research (continued)
Page 4: HHV6 Research
Page 5: Stealth Virus Research, General Virus Research and Relevant Books
Page 1: Enteroviral and Post-polio Research
Page 2: Enteroviral and Post-polio Research (continued)
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