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Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and Human Herpes Virus-6 Coinfections in the Blood of Patients With Autistic Spectrum Disorders Garth L. Nicolson,1* Robert Gan,1 Nancy L. Nicolson,1 and Joerg Haier1,2 1The Institute for Molecular Medicine, Huntington Beach, California 2Department of Surgery, University Hospital, Munster, Germany We examined the blood of 48 patients from central and southern California diagnosed with autistic spectrum disorders (ASD) by using forensic polymerase chain reaction and found that a large subset (28/48 or 58.3%) of patients showed evidence of Mycoplasma spp. infections compared with two of 45 (4.7%) age-matched control subjects (odds ratio = 13.8, P < 0.001). Because ASD patients have a high prevalence of one or more Mycoplasma spp. and sometimes show evidence of infections with Chlamydia pneumoniae, we examined ASD patients for other infections. Also, the presence of one or more systemic infections may predispose ASD patients to other infections, so we examined the preva lence of C. pneumoniae (4/48 or 8.3% positive, odds ratio = 5.6, P < 0.01) and human herpes virus-6 (HHV- 6, 14/48 or 29.2%, odds ratio = 4.5, P < 0.01) coinfections in ASD patients. We found that Mycoplasma-positive and -negative ASD patients had similar percentages of C. pneumoniae and HHV-6 infections, suggesting that such infections occur independently in ASD patients. Control subjects also had low rates of C. pneumoniae (1/48 or 2.1%) and HHV-6 (4/48 or 8.3%) infections, and there were no coinfections in control subjects. The results indicate that a large sub- set of ASD patients shows evidence of bacterial and/or viral infections (odds ratio 1⁄4 16.5, P < 0.001). The significance of these infections in ASD is discussed in terms of appropriate treatment. Autism was first identified in 1943 (Kanner, 1943), and autism patients generally suffer from an inability to communicate properly, form relationships with others, and respond appropriately to their environments. Autism patients often display repetitive actions and develop troublesome fixations with specific objects, and they are often sensitive to certain sounds, tastes, and smells. Autism patients do not all share the same signs and symp- toms but tend to share certain social, communication, motor, and sensory problems that affect their behavior in predictable ways (Berney, 2000). Autism and related dis- orders have been recently placed into a multidisorder category called autistic spectrum disorders (ASD), which includes autism, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), and other disorders (Keen and Ward, 2004). The criteria for diagnosis of ASD are, in general terms, the presence of a triad of impairments in social interaction, communication, and imagination (Wing et al., 2002). These signs and symptoms are thought to be due to abnormalities in brain function or structure and are thought to have a genetic basis (Folstein and Rosen-Sheidley, 2001; Veenstra-Vanderweele et al., 2003). The incidence of ASD is currently estimated at 1 in 1,000 children, and in genetically predisposed families the disorder is *100 times higher in incidence than in the general population (Folstein and Rosen-Sheidley, 2002). The concordance rate in monozygotic twins is 70–90%, whereas in dizygotic twins the rate is close to 0%, suggesting a strong genetic component (Veenstra- Vanderweele et al., 2003). In some patients, there are also a number of other less specific chronic signs and symptoms. Among these are fatigue, headaches, gastrointestinal and vision prob- lems, and occasional intermittent low-grade fevers and other signs and symptoms that are generally excluded in the diagnosis of ASD. These suggest that a subset of ASD patients may suffer from bacterial or viral infections (Takahashi et al., 2001). There are several reasons for this, including the nonrandom or clustered appearance of ASD, sometimes in immediate family members or par- ticular regions, the presence of certain signs and symptoms associated with infection, the cyclic course of the illness, and in some cases its response to antimicrobial therapies. Although no single underlying cause has been established for ASD, there is growing awareness that ASD can have an infectious nature that may be a cofactor for the illness or appear as an opportunistic infection(s) that can aggravate patient morbidity (Takahashi et al., 2001; Yamashita et al., 2003; Libbey et al., 2005). Identifying systemic infections, such as those produced by Myco- plasma species (Huang et al., 1998; Nijs et al., 2002; Nicolson et al., 2003a,b, 2005a), Chlamydia pneumoniae (Chia and Chia, 1999; Nicolson et al., 2003a,b), and human herpes virus-6 (HHV-6; Braun et al., 1997; Campadelli-Fiume et al., 1999; Nicolson et al., 2003a,b), is likely to be important in determining the treatment strategies for many ASD patients. These infections can penetrate the CNS and are associated with other neurological diseases (Nicolson et al., 2002). In addition, heavy metal, chemical, and environmental exposures also appear to be important in ASD (Eppright et al., 1996; Colborn, 2004; Davidson et al., 2004). Here we examined ASD patients to determine whether a subset of patients shows evidence of infection with Mycoplasma spp., C. pneumoniae, or HHV-6. Because these infections can cause neurological signs and symptoms (Baseman and Tully, 1997; Nasralla et al., 1999, 2000; Nicolson et al., 2003a), they may be important in ASD. Previously we found that children of Mycoplasma- positive Gulf War veterans were over 18 times more likely to come down with Mycoplasma fermentans than the general population (Nicolson et al., 2003c), and ASD diagnoses were found in their children. In addition, examination of a group of autism patients from civilian families revealed that there was a high incidence of mycoplasmal infections, including M. fermentans, M. pneumo- niae, and M. hominis (Nicolson et al., 2005b). Because mycoplasmal infections can often be found as coinfections with C. pneumoniae or HHV-6 (Nicolson et al., 2003a,b, 2005a), we examined ASD patients to see whether they had evidence of coinfections of Mycoplasma spp., C. pneumoniae, and HHV-6. MATERIALS AND METHODS Patients All ASD patients (N 1⁄4 48) were randomly recruited from families in contact with patient support groups and were referred from central and southern California physicians after diagnosis with ASD according to the International classification of diseases (ICD-10) and the Diagnostic and statistical manual of mental disorders (DSM-IV). All patients were assessed via the Autism Diagnostic Interview-Revised (ADI-R; Lord et al., 1997) and Childhood Autism Rating Scale (CARS; Van Bourgondien et al., 1992; Pilowsky et al., 1998). All of the patients in the study were ASD patients; most (45/48) had a diagnosis of autism, and six of 48 were diagnosed with ADD (three of which were also diagnosed with autism) and nine autism patients with Asperger’s syndrome. Patients also underwent a medical history, a sign/symptom illness survey was taken, and they had routine laboratory tests. Additionally, all parents were questioned about medication use during the 3 months prior to the study, and patients had to be free of antibiotic treatment for 2 months prior to blood collection. Control subjects were from families randomly recruited for unrelated studies (N 1⁄4 45); they had to be free of any disease or behavioral disorder, and they had not undergone antibiotic treatment for 3 months prior to blood collection. Blood Collection Blood was collected in EDTA-containing tubes and im- mediately brought to ice-bath temperature as described previously (Nijs et al., 2002; Nicolson et al., 2003a–c, 2005a). Samples were shipped with wet ice by overnight air courier to the Institute for Molecular Medicine for analysis. All blood samples were blinded. Whole blood (50 ll) was used for prep- aration of DNA using Chelex (Bio-Rad, Hercules, CA), as follows. Blood cells were lysed with nano-pure water (1.3 ml) at room temperature for 30 min. After centrifugation at 13,000g for 2 min, the supernatants were discarded. Chelex solution (200 ll) was added, and the samples were incubated at 568C and at 1008C for 15 min each. Aliquots from the centrifuged samples were used immediately for polymerase chain reaction (PCR) or flash frozen and stored at –708C until use. Multiple aliquots were used for experiments on all patient samples. Detection of Mycoplasma by Forensic PCR Amplification of the target gene sequences (Nicolson et al., 2003a,b, 2005a) was performed in a total volume of 50 ll PCR buffer (10 mM Tris-HCl, 50 mM KCl, pH 9) containing 0.1% Triton X-100; 200 lm each of dATP, dTTP, dGTP, and dCTP; 100 pmol of each primer; and 0.5– 1 lg of chromosomal DNA. Purified mycoplasmal DNA (0.5–1 ng of DNA) was used as a positive control for amplification. The efficiency of the PCR process was monitored by amplification of b-actin mRNA. Additional primer sets were used to confirm the species specificity of the reaction (Nic- AQ1 olson et al., 2003a–c, 2005a). The amplification was carried out for 40 cycles with denaturing at 948C and annealing at 608C (genus-specific primers and M. penetrans) or 558C (M. pneumoniae, M. hominis, M. fermentans). Extension temperature was 728C in all cases. Finally, product extension was performed at 728C for 10 min. Negative and positive controls were present in each experiment. The amplified samples were run on a 1% agarose gel containing ethidium bromide in TAE buffer (0.04 M Tris-acetate, 0.001 M EDTA, pH 8.0). After denaturing and neutralization, Southern blotting was performed. The DNA was amplified for 30 cycles using standard cycle parameters and the product evaluated by agarose gel electrophoresis. The efficiency of the PCR process was monitored by amplification of b-actin mRNA. The presence of amplification inhibitors was evaluated by spiking negative samples. C. pneumoniae-specific sequence of the PCR product was confirmed by Southern blot and dot-blot hybridization with a 21-mer internal probe: 50 -CGTTGAGTCAACGACTTAAGG-30 30 -end-labelled with digoxigenin-UTP or 32P-labeled probe. HHV-6 Detection by Forensic PCR PCR detection of HHV-6A was performed as described above, except that the conditions and primers differ, and plasma was used for polynucleotide isolation to detect active infections or cell-released virus (Nicolson et al., 2003a,b). PCRs were carried out using the following HHV-6A-specific primers: 50-GCGTTTTCAGTGTGTAGTTCGGCAG-30 (up- stream) and 50-TGGCCGCATTTCGTACAGATACGGA- GG-30 (downstream). The nucleotides were amplified for 30 cycles with standard cycle parameters, and the product was evaluated by agarose gel electrophoresis. The efficiency of the PCR process was monitored by amplification of b-actin mRNA. The presence of amplification inhibitors was evaluated by spiking negative samples. HHV-6A-specific oligonucleotides in the PCR product were identified by Southern blot and dot-blot hybridization using a 21-mer internal probe: 50- Type Culture Collection (Manasses, VA). The primers produced the expected amplification product size in all test species, which was confirmed by hybridization using the appropriate 32P-labeled internal probe (Nasralla et al., 1999). Amounts as low as a few femtograms of purified DNA were detectable for all species with the specific internal probes. There was no cross-reactivity between the internal probes of one species and the PCR product from another species (Nasralla et al., 2000; Nicolson et al., 2003a–c). The techni- ques used have been validated in various studies (see, e.g., Berg et al., 1996; Bernet et al., 1995). Statistical Analysis Subjects’ demographic characteristics were assessed via descriptive statistics and Student’s t-tests (independent-samples test, t-test for equality of means, two-tailed). The 95% confidence interval was chosen for minimal significance. Odds ratios were calculated by using logistic regression (logit method) in Statistica 5.5 (Statsoft, Tulsa, OK). In some cases, Pearson v2 test was performed to compare prevalence data between patients and control subjects. RESULTS Patients and Control Subjects ASD patients and control subjects were approxi- mately similar in age (control subjects mean age 1⁄4 8.4; ASD patients mean age 1⁄4 7.9). ASD patients differed significantly according to sex distribution (P < 0.05); 75% of the patients were male, whereas 25% of the patients were female. Similarly, 62.2% of control subjects were male, whereas 37.8% were female. Patients were from central and southern California and resided in approximately equally in rural and urban environments (Table I). T1 Bacterial and Viral Infections in ASD Patients By using PCR, we examined ASD patients’ blood for the presence of bacterial and viral infections. Evi- dence for Mycoplasma spp. infections was found in 28 of 48 or 58.3% of ASD patients and two of 45 or 4.7% age-matched control subjects (odds ratio 1⁄4 13.8, P < 0.001). C. pneumoniae infections were found in four of 48 or 8.3% of ASD patients and in one of 45 or 2.1% of control subjects (odds ratio 1⁄4 5.6, P < 0.01). We also examined the incidence of HHV-6 infections in ASD patients and found that 14 of 48 or 29.2% of ASD patients were positive compared with four of 45 or 8.8% age-matched control subjects (odds ratio 1⁄4 4.5, P < 0.01). We did not find any multiple coinfections in control subjects . The rate of positive results in control subjects was similar to that in previous studies (Nasralla et al., 2000; Nicolson et al., 2003a–c, 2005). The differences between infections in ASD patients and control subjects were highly significant (odds ratio 1⁄4 16.5, P < 0.001). Significant differences were not found in the prevalence of infections between urban and rural patients, between male and female patients, or between autism and other ASD diagnoses. Multiple Coinfections in ASD Patients We studied multiple infections in patients by examining whether patients who were positive (or nega- tive) for one type of infection also tested positive for other infections. Eight of fourteen patients with HHV-6 positive results (57.1%) were also positive for mycoplas- mal infections. C. pneumoniae infections were observed in two of four mycoplasma-positive ASD patients and two of four mycoplasma-negative patients. Therefore, we did not find a preference for particular multiple infections in patient subsets. Multiple mycoplasmal infections were found in 12 of 48 or 25% of ASD patients; only M. fermentans plus other species were found. We exam ined 45 control subjects who did not show clinical signs and symptoms and found that only two were positive for a single mycoplasma species (Mycoplasma pneumoniae. Differences between ASD patients and control subjects were highly significant. DISCUSSION Previously we found that chronic infections in Gulf War veterans diagnosed with Gulf War illness could also be found in symptomatic family members, including their children (Nicolson et al., 2003c). In the families chosen for this study, chronic illnesses were not reported until after the veteran in the family returned from the Gulf War. Interestingly, though not reported, common diagnoses of illness in the children of Gulf War veterans with mycoplasmal infections included ASD-like illnesses, among others, and we found the same infection, primar ily M. fermentans, in both the sick adults and the children in these families. The data suggested that the M. fermentans was likely passed from the veterans to their children (Nicolson et al., 2003c). Although preliminary and not carefully analyzed or studied further, this result suggested that infections might be present in ASD patients. Therefore, we examined a small group of patients (28 patients with autism-like disorders, age range 3–12 years) in cen- tral California for evidence of mycoplasmal infections, and we found that slightly over one-half were positive for one of four species of Mycoplasma (Nicolson et al., 2005b). In contrast to the children in military families among whom primarily one species of Mycoplasma was found (usually M. fermentans), most ASD patients in central California were found to have single or multiple mycoplasmal infections involving M. pneumoniae, M. fermentans, M. hominis, or M. genitalium. We found simi- lar results in the present study, but, in addition to infec- tions with Mycoplasma spp., we also examined two other commonly found infections in chronically ill patients, C. pneumoniae and HHV-6 (Nicolson et al., 2003a,b). The results suggested that infections are a common feature in ASD. Consistent with this hypothesis is the finding that autism occurs at greater prevalence during periods of more frequent hospitalizations for bronchitis or pneumonia (Tanoue et al., 1988), and maternal viral infections during the second trimester of pregnancy are associated with increased risk of autism in the offspring (Ciaranello and Ciaranello, 1995; Wilkerson et al., 2002). Infections are thought to play important roles in a variety of neurodevelopmental diseases, including ASD (Horning et al., 1999; Nicolson et al., 2002; Libbey et al., 2005). Such infections could be involved in the etiology of the disease, or more likely they could cause comorbid states (Nicolson et al., 2003a,b, 2005). We found a higher prevalence of Mycoplasma spp. (odds ratio 1⁄4 13.8), C. pneumoniae (odds ratio 1⁄4 5.6), and HHV-6 (odds ratio 1⁄4 4.5) among children diagnosed with ASD compared with age-matched control subjects. The PCR techniques used in the present study have been validated in other studies (Nicolson et al., 2003a–c, 2005). There are some similarities between the environmental exposures of Gulf War veterans and children with ASD. Both groups were given multiple vaccines prior to their illnesses, and heavy metals and chemicals have been found in both groups (Eppright et al., 1996; Boyd, 2004; Buttram, 2004; Davidson et al., 2004; Geier and Geier, 2004), but these findings are not universal (Jackson and Garrod, 1978). There are reports of clinical improvement with treatment for these environmental exposures (for review see Kidd, 2002). There were limitations in the present preliminary study, including sample size. Although all of the patients in the study were ASD patients, most (39/48) had a diagnosis of autism, and six of 48 were diagnosed with Asperger’s syndrome, wherease six of 48 were diagnosed with ADD (three of whom were also diagnosed with autism). Removal of the two sets of six patients from the analysis or analysis of the data by sex did not change the results or conclusions. Other factors, such as geogra- phy, family socioeconomic status, vaccination records, and family educational levels were not analyzed. There were also limitations in the diagnostic tests performed on patients. Future studies should include additional tests on the patients’ intellectual capacities with regard to abstract- ing and generalization as well as verbal and nonverbal communications. The infections found in ASD patients in the present and previous studies (Takahashi et al., 2001; AQ2 Yamashita et al., 2003; Libbey et al., 2003; Nicolson et al., 2003c, 2005) could have originated from vaccines or from opportunistic infections in immune-suppressed children. Bacterial contamination has been found in commercial vaccines, and in one study 6% of commercial vaccines were contaminated with mycoplasmas (Thornton, 1986). Thus the appearance of infections in children diagnosed with ASD may eventually be linked to the multiple vaccines received during childhood either as a source or from opportunistic infections in immune;suppressed recipients of multiple vaccines. Although the etiology of ASD is currently unknown and is thought to involve both genetic and environmental factors (Lipkin and Hornig, 2003; Libbey et al., 2005), the infections found in ASD patients should be considered along with other factors in the management of these disorders (Kidd, 2002). 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Nicolson GL, Gan R, Haier J. 2003a. Multiple co-infections (Mycoplasma, Chlamydia, human herpesvirus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. Acta Pathol Microbiol Immunol Scand 111:557–566. AQ2 Nicolson GL, Nasralla M, Gan R, Haier J, De Meirleir K. 2003b. Evidence for bacterial (Mycoplasma, Chlamydia) and viral (HHV-6) coin- fections in chronic fatigue syndrome patients. J Chronic Fatigue Syndr 11:7–20. Nicolson GL, Nasralla M, Nicolson NL, Haier J. 2003c. High prevalence of mycoplasmal infections in symptomatic (chronic fatigue syndrome) family members of mycoplasma-positive gulf war illness patients. J Chronic Fatigue Syndr 11:21–36. Nicolson GL, Gan R, Haier J. 2005a. Evidence for Brucella spp. and Mycoplasma spp. coinfections in blood of chronic fatigue syndrome patients. J Chronic Fatigue Syndr 12:5–17. Nicolson GL, Nicolson GL, Gan R, Haier J. 2005b. 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Genetics of childhood disorders. XLVI. Autism, part 5, genetics of autism. J Am Acad Child Adolesc Psychiatry 42:116–118. Wilkerson DS, Volpe AG, Dean RS, Titus JB. 2002. Perinatal complica- tions as predictors of infantile autism. Int J Neurosci 112:1085–1098. Wing L, Leekam SR, Libby SJ, Gould SJ, et al. 2002. The diagnostic interview for social and communication disorders: background, inter- rater reliability and clinical use. J Child Psychol Psychiatry 43:307–325. Yamashita Y, Fujimoto C, Nakajima E, Isagai T, Matsuishi T. 2003. Pos- sible association between congenital cytomegalovirus infection and autistic disorder. J Autism Dev Disord 33:355–459. *Correspondence to: Prof. Garth L. Nicolson, Office of the President, The Institute for Molecular Medicine, 16371 Gothard Street H, Huntington Beach, California 92647. E-mail: gnicolson@immed.org Received 24 January 2006; Revised 13 November 2006; Accepted 22 November 2006 Published online 00 Month 2007 in Wiley InterScience (www. interscience.wiley.com).
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Clinical Testing Suggestions For chronic illnesses (CFS, FMS, RA, Lupus, neurodegenerative diseases, among other illnesses) that could have an infectious component, The Institute for Molecular Medicine suggests the following lab tests (codes are CPT codes or test description/ordering codes): 1. Mycoplasma Test Panel (CPT: 87581)—Mycoplasma species tested by PCR. This is a Mycoplasma test on the 3 most common species of Mycoplasma (M. pneumoniae, M. ferementans, M. hominis). Individual tests species tests can also be ordered (M. pneumoniae, M. ferementans or M. hominis). Justification: Almost 60% of CFS/FMS and 50% of Rheumatoid Arthritis (RA) and 50% other autoimmune patients have one or more intracellular, systemic mycoplasmal infections similar to those found in a variety of chronic illnesses [Nicolson et al. Mycoplasmal infections in chronic illnesses: Fibromyalgia and Chronic Fatigue Syndromes, Gulf War Illness, HIV-AIDS and Rheumatoid Arthritis. Medical Sentinel 1999; 5: 172-176]. Ultrasensitive and ultraspecific mycoplasma tests can only be done by a small number of labs. Recommended Labs: Unevx Laboratories, 1664 N. Virginia St., Reno, NV 89557, Tel: 775-682-8280, Fax: 775-682-8290 (Test Description Code: MYCP) Spiro Stat Technologies, 1004 Garfield Dr., Bld 340, Lubbock, TX 79416; Tel: 806-885-2929, Fax: 806- 885-2933, Specimen Requirements: Contact laboratory for a specimen kit. For Unevx, the blood is collected in a Lavender Top EDTA tube, mixed and shipped (same day) in an insulated container overnight air courier to arrive within 24 hours. For Spiro Stat, the blood is collected in 2 Purple Top EDTA tubes. 2. Chlamydia pneumoniae Test (CPT: 87486)—Chlamydia pneumoniae tested by PCR. Justification: Many CFS, FMS, MS, RA and other patients have this systemic infection along with viral infection(s). We were among the few labs that developed the molecular tests that are now done for this type of infection. Recommended Lab: Unevx Laboratories, 1664 N. Virginia St., Reno, NV 89557, Tel: 775-682-8280, Fax: 775-682-8290 (Test Description Code: CHLP) Specimen Requirements: Contact laboratory for a specimen kit. The blood is collected in (1) Lavender Top EDTA tube and (1) Red Top Serum Separator Tube (separated), and shipped (same day) in an insulated container overnight air courier to arrive within 24 hours. 3. Lyme Borrelia burgdorferi Test (CPT: 86617)—Borrelia burgdorferi (Lyme Disease) by Western Blot analysis. Justification: Many CFS, FMS and RA patients have this systemic infection (diagnosed as Lyme Disease) along with other co-infection(s) (Nicolson et al. Chronic Fatigue Syndrome patients subsequently diagnosed with Lyme Disease Borrelia burgdorferi: evidence for Mycoplasma species co-infections. J Chronic Fatigue Syndr 2008; 14(4):5-17. Recommended Lab: IGeneX Laboratories of Palo Alto, CA (http://www.igenex.com/). Specimen Requirements: Contact laboratory for a specimen kit. Collect in Red Top Tube, separate, and send in clear tube. Store in Refrigerator until shipment. Ship within one day of collection at Room Temperature. 4. HHV-6 Test (CPT: 87532)—Human herpes virus 6 (HHV-6) test by PCR. Justification: Many CFS and some FMS patients have this systemic viral infection, and it should be tested for in any autoimmune illness (Nicolson et al. Multiple co-infections (Mycoplasma, Chlamydia, Human Herpesvirus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. Acta Pathol Microbiol Immunol Scand 2003; 111: 557-566). Recommended Lab: Unevx Laboratories, 1664 N. Virginia St., Reno, NV 89557, Tel: 775-682-8280, Fax: 775-682-8290 (Test Description Code: HHVP) Specimen Requirements: Contact laboratory for a specimen kit. The blood is collected in (1) Lavender Top EDTA tube and (1) Red Top Serum Separator Tube (separated), and shipped (same day) in an insulated container overnight in any autoimmune illness (Nicolson et al. Multiple co-infections (Mycoplasma, Chlamydia, Human Herpesvirus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. Acta Pathol Microbiol Immunol Scand 2003; 111: 557-566). Recommended Lab: Unevx Laboratories, 1664 N. Virginia St., Reno, NV 89557, Tel: 775-682-8280, Fax: 775-682-8290 (Test Description Code: HHVP) Specimen Requirements: Contact laboratory for a specimen kit. The blood is collected in (1) Lavender Top EDTA tube and (1) Red Top Serum Separator Tube (separated), and shipped (same day) in an insulated container overnight air courier to arrive within 24 hours. 5. CMV Test 07034 (CPT: 87496)—Cytomegalovirus (CMV) test by nested PCR. Justification: Many CFS and FMS patients have this systemic viral infection, and it should be tested for in any autoimmune illness. Recommended Lab: Unevx Laboratories, 1664 N. Virginia St., Reno, NV 89557, Tel: 775-682-8280, Fax: 775-682-8290 (Test Description Code: HHVP) Specimen Requirements: Contact laboratory for a specimen kit. The blood is collected in (1) Lavender Top EDTA tube and (1) Red Top Serum Separator Tube (separated), and shipped (same day) in an insulated container overnight air courier to arrive within 24 hours. Tests must be ordered by a physician, and tests must be pre-paid or pre-approved by an insurance carrier (private insurance or Medicare, Medicaid or Medical). The Institute for Molecular Medicine website is www.immed.org. On this site you will find publications and documents on CFS/ME, FMS, autoimmune diseases and other chronic illnesses. Prof. Garth Nicolson President & Chief Scientific Officer, The Institute for Molecular Medicine (www.immed.org)
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20 mars 2012 2 20 /03 /mars /2012 07:18
Le texte qui a été publié à l’automne dernier, dans les Archives of Toxicology, est véritablement apologique. Si l’on en croit CT Chapasis et al., de l’Université de Patras, le zinc (et en l’occurrence sa carence) serait la clé de l’apparition et du développement d’innombrables affections. L’oligo élément jouerait un rôle critique dans des processus aussi divers que l’homéostasie, les défenses immunitaires, le stress oxydatif, l’apoptose ou le vieillissement cellulaire ; un manque compliquerait ou accélérerait l’évolution de plusieurs pathologies chroniques, dont athérosclérose, néoplasies diverses, affections auto immunes, affections dégénératives liées à l’âge, maladie de Wilson etc. Et les Grecs de rappeler enfin qu’il a déjà été rapporté que la prescription de zinc améliorerait plusieurs des conditions pathologiques énumérées ci-dessus… Laissons aux auteurs la responsabilité de leurs assertions et penchons nous sur une nouvelle publication encore plus récente. Il s’agissait, cette fois, d’évaluer l’intérêt du zinc dans la prise en charge de la pneumonie sévère de l’enfant. Pour ce faire, les auteurs ont réalisé une étude en double aveugle, individualisant deux bras à partir de 352 enfants de 6 à 59 mois souffrant d’une pneumonie sévère, le premier recevant 12 mg/ J (âge de moins d’un an) ou 20 mg/J (âge > 12 mois) de zinc en complément d’une antibiothérapie adaptée et les seconds le placebo. Il est apparu, dans ces conditions, que si la normalisation des signes respiratoires, de la fièvre et de la saturation en oxygène restaient comparables dans les deux groupes, tel n’était pas le cas de la mortalité, qui passait de 7/176 (4,0 %) dans le groupe zinc à 21/176 (11,9 %) dans le second [Risque relatif 0,33, intervalle de confiance à 95 % : 0,15-0,76]. Des résultats encore plus remarquables si on individualisait les enfants VIH+, la mortalité chutant de 7/27 dans le groupe placebo à 0/28 dans le groupe complémenté. Au total, le zinc ne raccourcissait pas l’évolution de l’infection, mais il en améliorait très clairement le pronostic… Le zinc, (nouvel) élément majeur de la prise en charge de nombreux patients en médecine interne ou en infectiologie ? Sans doute, mais peut-être aussi dans des conditions particulières de carence puisque la seconde étude a été réalisée à l’hôpital Mulago, Université de Makerere, Ouganda, un pays ou les carences sont loin d’être exceptionnelles. Ce qui semble certain aujourd’hui, c’est qu’à l’instar d’autres composés comme la vitamine D, le zinc joue un rôle essentiel dans les processus de défense immunitaire et qu’une insuffisance pourrait être véritablement dévastatrice. Un concept à garder en mémoire quand les patients paraissent (trop) démunis. Dr Jack Breuil Srinivasan MG et coll. Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial. BMC Medicine, 2012 ; 10 :14 17/03/2012
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19 mars 2012 1 19 /03 /mars /2012 17:13

Eude publiée dans le Journal of Agricultural and Food Chemistry, qui montre que manger quelques baies (fraises, myrtilles, cassis) par jour "peut contribuer à endiguer le déclin des capacités cognitives et autres symptômes du vieillissement, grâce à leur forte teneur en antioxydants, qui protègent les cellules des effets néfastes des radicaux libres".

 

Le quotidien régional explique que les chercheurs ont "épluché la littérature scientifique sur l'impact des baies au niveau cellulaire, et sur les fonctions cognitives chez les humains et les animaux".

 

L'étude s'appuie, de plus, sur des travaux antérieurs ayant montré que les baies permettaient de "nettoyer le cerveau" des protéines toxiques.

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19 mars 2012 1 19 /03 /mars /2012 16:35

« des facteurs génétiques influencent la réponse immunitaire aux vaccins contre la maladie d'Alzheimer, l'une des pistes thérapeutiques les plus prometteuses contre cette pathologie ». 

Travaux chez la souris du Pr Pierre Aucouturier et de son équipe du Laboratoire Système Immunitaire et Maladies Conformationnelles (Inserm/UPMC) de l'Hôpital Saint-Antoine, publiés dans The Journal of Immunology.

« ces travaux montrent, qu'en plus des molécules du Complexe Majeur d'Histocompatibilité (CMH), qui présentent l'antigène vaccinal aux cellules immunitaires, des facteurs génétiques, contrôlant certaines cellules immunitaires, influencent la qualité de la réponse à la vaccination ».


« Ces résultats pourraient permettre de prévenir des réactions neuro-inflammatoires, obstacle majeur à l'utilisation du vaccin chez l'homme »

 

L’essentiel de la psycho, février 2012

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19 mars 2012 1 19 /03 /mars /2012 16:30

Selon une étude américaine, « manger en excès favoriserait les troubles cognitifs, notamment les pertes de mémoire. 

Ainsi, les gros mangeurs  (plus de 2.100 calories par jour) doublent le risque de voir leur mémoire décliner. 

Ils sont plus exposés à souffrir de déficience cognitive légère, un stade intermédiaire entre une perte de mémoire normale due à l'âge et l'apparition de la maladie d'Alzheimer. 

En revanche, les personnes âgées qui maintiennent une alimentation pauvre en calories à un âge avancé ont plus de chance de prévenir le risque de développer la maladie d'Alzheimer ».

« les chercheurs ont analysé les habitudes alimentaires et la consommation d'alcool de seniors âgés de 70 à 89 ans (non atteints de la maladie d'Alzheimer), puis les ont soumis à des tests de mémoire. 

Les participants ont été partagés en trois catégories : les gros mangeurs (2.100 à 6.000 kcal/jour), les appétits moyens (1.500 à 2.100) et les petits appétits (600 à 1.500). Résultat, le risque était deux fois plus élevé chez les plus gourmands ».

« pour prévenir la perte de mémoire liée à l'âge, l'idéal est de réduire le nombre de calories, de faire 4 repas par jour, de manger équilibré (poisson, œufs, laitages, céréales, fruits, légumes...). Mais aussi de pratiquer une activité physique régulière ».

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19 mars 2012 1 19 /03 /mars /2012 11:46

« près de 30 ans après sa découverte par Stanley Prusiner, le prion continue d'intriguer les scientifiques. 

Cette protéine, dont la nocivité dépend non pas de sa composition chimique mais de sa forme, est une véritable anomalie dans l'arsenal des composants de la vie ».


Yves Christen, de la Fondation Ipsen, qui vient d'organiser à Paris un colloque sur le sujet, remarque ainsi que « dans leur conformation normale, les prions participent aux fonctions normales des neurones. Mais dans certaines circonstances, ils adoptent une configuration en feuillets. Ils forment alors des agrégats pathogènes ».


« ce Janus biologique possède une autre capacité longtemps interdite par le dogme en vigueur : il transmet sa toxicité aux protéines voisines par le biais d'un mécanisme de mimétisme mal connu ».


« Chez l'animal comme chez l'homme, la responsabilité de ces curieux objets a été démontrée pour plusieurs encéphalopathies mortelles : maladie de la vache folle (ESB), tremblante du mouton (« scrapie »), Kuru et maladie de Creutzfeldt-Jakob. 

Avec le temps, les prions anormaux s'agglomèrent. Ils forment des amas asphyxiant les neurones et donnant au cerveau un aspect spongiforme ».


« à l'université de Lund, en Suède, Patrik Brundin travaille sur la maladie de Parkinson, soupçonnée elle aussi de faire partie de la grande famille des pathologies «prionlike»

C'est une protéine courante (alpha-synucléine) s'accumulant dans les cellules nerveuses qui semble responsable de cette évolution. […] Ron Kopito, de l'université de Stanford, s'intéresse lui aussi à ce concept très en vogue chez les neurologues. 

Selon lui, l'agrégation de molécules est un phénomène courant dans la nature et pourrait expliquer de très nombreux troubles cognitifs ».
« toute cette effervescence réjouit Stanley Prusiner » et interroge ce dernier. 

Le prix Nobel de médecine 1997 déclare ainsi que « le prion est une protéine quasi vivante. Mais ce n'est pas non plus une évolution monstrueuse de la nature. C'est une molécule très courante ».


A la question « La recherche dans ce domaine est-elle suffisante ? », le chercheur répond : « Pas du tout et c'est proprement scandaleux. Aux Etats-Unis, cela ne représente que 4% des financements fédéraux, contre près de 20% qui vont au cancer. C'est d'autant plus injuste que toutes les maladies mentales comme Alzheimer sont en augmentation rapide dans tous les pays à cause du vieillissement des populations ».


Stanley Prusiner ajoute, à propos de la malade d’Alzheimer : « Aucun des médicaments sur le marché n'est efficace. Leur rapport bénéfice-risque est très défavorable. 

Il faudrait les retirer de la vente. Le problème, c'est que le pipeline de l'industrie pharmaceutique dans le domaine des maladies neurodégénératives est pratiquement vide. […] J'aimerais me tromper, mais je ne crois pas à une pilule miracle pour soigner la maladie d'Alzheimer. 

Il faudra sûrement se tourner vers une association de plusieurs molécules ».

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19 mars 2012 1 19 /03 /mars /2012 11:38

 « depuis plus de 10 ans, des enquêtes partout dans le monde font état d’une baisse du nombre de spermatozoïdes chez les hommes en âge de procréer. 

Plusieurs hypothèses, notamment liées à l’environnement, aux pesticides, aux produits chimiques ont été évoquées pour expliquer une telle évolution ».

« une enquête américaine publiée dans Human Reproduction indique en tout cas qu’une alimentation trop riche en graisses animales affecterait la qualité du sperme. 

En revanche, la consommation d’omégas-3 serait associée à une meilleure qualité ».

 

Ce travail, « conduit entre décembre 2006 et août 2010 par le Pr Jill Attaman (Harvard Medical School, Boston), concerne 99 hommes interrogés par questionnaire sur leurs habitudes alimentaires. Le sperme de 23 d’entre eux a par ailleurs été analysé ».

« c’est en faisant une corrélation entre la qualité des spermatozoïdes (nombre, mobilité, vitalité, formes anormales…) et le mode d’alimentation qu’ils ont pu découvrir l’impact négatif de certaines graisses. Les hommes mangeant le plus de graisses saturées avaient un nombre total de spermatozoïdes de 35% inférieur par rapport à ceux qui en mangeaient le moins, ainsi qu’une concentration spermatique inférieure de 38% ».

« la relation entre alimentation grasse et qualité du sperme serait donc due à la consommation de graisses saturées (charcuterie, chips, viennoiseries, certaines viandes, beurre, huile de palme…) connues pour représenter aussi un facteur de risque de maladies cardio-vasculaires ».

« s’il s’agit de la plus importante étude évaluant l’influence du régime sur la fertilité, les effectifs examinés sont assez faibles ; ces résultats intéressants nécessitent d’être reproduits à une plus grande échelle ».

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17 mars 2012 6 17 /03 /mars /2012 09:29
Sciences et Avenir relève qu’« une étude récente montre que la présence de la bactérie H. pylori est associée à des niveaux élevés d’un biomarqueur important de la glycémie et du diabète ». Le magazine évoque ainsi une étude publiée dans le Journal of Infectious Diseases, expliquant que « des chercheurs de l’Université de New-York ont constaté que la présence de la bactérie H. pylori est associée à des niveaux élevés d'hémoglobine glycosylée (HbA1c), un biomarqueur important de la glycémie et du diabète. Cette association était plus forte chez les personnes obèses présentant un indice de masse corporelle au-dessus de la normale ». Sciences et Avenir note que les auteurs « ont émis l'hypothèse que H. pylori peut affecter les niveaux de deux hormones secrétées par l’estomac qui aident à réguler la glycémie. Ils suggèrent que l'éradication de la bactérie par des antibiotiques chez certaines personnes âgées obèses pourrait être bénéfique même si elles sont encore asymptomatiques au niveau du diabète ». Le magazine ajoute que « si [ces] résultats sont confirmés, «ils pourraient avoir d'importantes implications cliniques et de santé publique» estime Dani Cohen, de l’université de Tel Aviv qui a commenté l’article ».
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17 mars 2012 6 17 /03 /mars /2012 08:25
Pierre Bienvault note dans La Croix que « le rapport de la HAS sur l’autisme suscite de nombreuses critiques dans le monde de la psychiatrie. De nombreux professionnels affirment qu’ils sont prêts à évaluer leurs pratiques, mettant en avant un travail de recherche lancé en 2008 avec l’Inserm sur 82 enfants atteints ». Le journaliste relève ainsi que « nombre de psychiatres ont été très agacés par la «provocation» du Pr Jean-Luc Harousseau, le président du collège de la HAS, invitant les psychiatres à «se remettre en cause» et à évaluer leurs prises en charge ». Le Pr Bernard Golse, chef du service de pédopsychiatrie de l’hôpital Necker à Paris, déclare ainsi : « Nous n’avons pas attendu la HAS pour le faire ». Le Dr Jean-Michel Thurin, responsable du groupe « Recherches » à la Fédération française de psychiatrie, revient sur cette étude de 2008 et indique que les résultats « montrent une évolution positive de 50% en moyenne sur les différents critères de l’évaluation ». Pierre Bienvault ajoute que « de nombreux psychiatres estiment que le rapport de la HAS a été dicté par des «impératifs politiques» et le souci de ne «pas déplaire» aux associations de parents ». Le Pr Gérard Schmit (CHU de Reims) déclare que « de très nombreux pédopsychiatres, très dévoués, sont meurtris par ces recommandations bien peu scientifiques. […] Peut-être que certains psychiatres estiment toujours qu’il y a un lien entre le fonctionnement mental des parents et l’autisme de leur enfant. Mais je peux vous assurer que cette idée a été abandonnée depuis longtemps par la grande majorité d’entre nous. C’est un procès en sorcellerie que l’on nous fait ».
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