Belastungen mit chlororganischen Schadstoffen und Metallen bei Patienten mit Multipler Sklerose

Bei der Multiplen Sklerose (MS, Encephalomyelitis disseminata) handelt es sich um eine chronische, multilokuläre demyelinisierende Erkrankung des Zentralen Nervensystems, deren Ursachen bisher nicht exakt geklärt werden konnten. Die im ZNS disseminiert auftretenden Entzündungs- und Entmarkungsherde sind Ursache der sehr unterschiedlich verlaufenden klinischen Symptomatik u.a. mit multifokalen sensiblen Ausfällen, Paresen, Hirnnervenbefall, zerebellären Störungen, Blasenstörungen sowie neuropsychologischen Defiziten (z.B. hirnorganisches Psychosyndrom). Bei einer Prävalenz von etwa 50-100/100.000 und einer Inzidenz von 4-6/100.000 in Deutschland beträgt das Verhältnis von Frauen zu Männern etwa 2:1. Ätiologisch werden u.a. T-Zell-vermittelte Autoimmunmechanismen, Virusinfektionen, genetische Dispositionen und der Einfluß verschiedener Umweltfaktoren diskutiert. Es stellt sich auch die Frage nach erhöhten Belastungen mit chlororganischen Schadstoffen und Metallen

PTPRC (CD45) is not associated with multiple sclerosis in a large cohort of German patients

BACKGROUND: Since contradictory results have been reported, we reanalysed the 77C→G transition in exon 4 of the protein-tyrosine phosphatase receptor-type C (PTPRC also known as CD45) in a large cohort of German MS patients and controls. Different isoforms of the protein are expressed, depending on alternative splicing of exons 4 (CD45RA), 5 (CD45RB) and 6 (CD45RC) (CD45RO, exons 4–6 spliced out). The 77C→G transition does not change the amino acid sequence, but it is probably part of a motif necessary for splicing leading to the isoform CD45RA. The expression of CD45RA is increased in 77C/G heterozygous individuals. The aim of the study was to clarify the importance of the PTPRC 77C→G transition in our German cohort of MS patients. METHODS: PCR products of exon 4 were digested using endonuclease MspI. The resulting restriction fragments of the wildtype C allele are 198 and 62 bp in length. In the G allele an additional restriction site is present yielding fragments of 114 and 84 bp. RESULTS: The G allele was identified in 10 of the 347 controls (1.4%) and in 7 of 454 MS patients (0.8%; Table 1). No homozygous individuals were found either in the control or in the patient group. Genetic association between the PTPRC 77C→G transition and MS susceptibility was excluded in the MS cohort. In addition, subgrouping patients according to differences in the clinical course of MS or according to HLA-DRB1*15 status did not yield significant differences. CONCLUSIONS: The 77C→G transition in exon 4 of the PTPRC gene may contribute to MS susceptibility only in very few families, if at all, but it is not relevant for the majority of MS cases, including virtually all German patients

Belastungen mit chlororganischen Schadstoffen und Metallen bei Patienten mit Multipler Sklerose

Bei der Multiplen Sklerose (MS, Encephalomyelitis disseminata) handelt es sich um eine chronische, multilokuläre demyelinisierende Erkrankung des Zentralen Nervensystems, deren Ursachen bisher nicht exakt geklärt werden konnten. Die im ZNS disseminiert auftretenden Entzündungs- und Entmarkungsherde sind Ursache der sehr unterschiedlich verlaufenden klinischen Symptomatik u.a. mit multifokalen sensiblen Ausfällen, Paresen, Hirnnervenbefall, zerebellären Störungen, Blasenstörungen sowie neuropsychologischen Defiziten (z.B. hirnorganisches Psychosyndrom). Bei einer Prävalenz von etwa 50-100/100.000 und einer Inzidenz von 4-6/100.000 in Deutschland beträgt das Verhältnis von Frauen zu Männern etwa 2:1. Ätiologisch werden u.a. T-Zell-vermittelte Autoimmunmechanismen, Virusinfektionen, genetische Dispositionen und der Einfluß verschiedener Umweltfaktoren diskutiert. Es stellt sich auch die Frage nach erhöhten Belastungen mit chlororganischen Schadstoffen und Metallen

Extrapontine myelinolysis presenting as acute parkinsonism

BACKGROUND: Extrapontine myelinolysis presenting with extra pyramidal features suggestive of parkinsonism may be a challenging clinical syndrome. Clinicians should maintain their vigilance while correcting electrolyte imbalances, especially with associated co-morbidity. CASE PRESENTATION: A 41-year-old woman presented with acute parkinsonism like features while on a holiday. This followed slow correction of hyponatraemia after repeated vomiting. MRI changes were suggestive of Extrapontine myelinolysis(EPM). This case is at variance with four previous cases reported in the medical literature in that the patient made a full clinical recovery and the MR changes resolved with symptomatic support alone. CONCLUSION: Extrapontine myelinolysis could make a complete recovery with symptomatic support alone. During hyponatraemia correction, rapid osmotic shifts of fluid that cause hypernatremia, causes myelinolysis rather than absolute serum sodium level. Even gradual correction of hyponatraemia can produce myelinolysis, especially with pre-existing malnourishment, alcoholism, drug misuse, Addison's disease and immuno-suppression. Pallidial sparing is typical of EPM in MRI scans

Experience of gratitude, awe and beauty in life among patients with multiple sclerosis and psychiatric disorders

Background: Feelings of gratitude and awe facilitate perceptions and cognitions that go beyond the focus of illness and include positive aspects of one's personal and interpersonal reality, even in the face of disease. We intended to measure feelings of gratitude, awe, and experiences of beauty in life among patients with multiple sclerosis and psychiatric disorders, particularly with respect to their engagement in specific spiritual/religious practices and their life satisfaction. Methods: We conducted a cross-sectional survey with standardized questionnaires to measure engagement in various spiritual practices (SpREUK-P) and their relation to experiences of Gratitude, Awe and Beauty in Life and life satisfaction (BMLSS-10). In total, 461 individuals (41 +/- 13 years; 68% women) with multiple sclerosis (46%) and depressive (22%) or other psychiatric disorders (32%) participated. Results: Among participants, 23% never, 43% rarely, 24% often, and 10% frequently experienced Gratitude. In contrast, 41% never, 37% rarely, 17% often, and 6% frequently experienced Awe. Beauty in Life was never experienced by 8% of the sample, and 28% rarely, 46% often, and 18% frequently experienced it. Gratitude (F=9.2; p=.003) and Beauty in Life (F=6.0; p=.015) were experienced significantly more often by women than men. However, the experience of Awe did not differ between women and men (F=2.2; n.s.). In contrast to our hypothesis, Gratitude/Awe cannot explain any relevant variance in patients' life satisfaction (R-2=.04). Regression analyses (R-2=.42) revealed that Gratitude/Awe can be predicted best by a person's engagement in religious practices, followed by other forms of spiritual practices and life satisfaction. Female gender was a weak predictor and underlying disease showed no effect. Conclusions: Gratitude/Awe could be regarded as a life orientation towards noticing and appreciating the positive in life - despite the symptoms of disease. Positive spirituality/religiosity seems to be a source of gratitude and appreciation in life, whereas patients with neither spiritual nor religious sentiments (R-S-) seem to have a lower awareness for these feelings

Diagnostik arbeitsbedingter Erkrankungen und arbeitsmedizinisch-diagnostische Tabellen

Eine ganze Reihe von beruflichen Belastungen und ungünstigen Arbeitsbedingungen kann zu zahlreichen berufsbedingten Erkrankungen und Beschwerden führen, von denen nur ein kleiner Teil als Berufskrankheit oder Arbeitsunfall anerkannt wird. Der größere, versicherungsrechtlich nicht anerkannte Teil gilt als "arbeitsbedingte Erkrankung" im engeren Sinne. Es sind Erkrankungen und Beschwerden, die beruflich verursacht, teilweise beruflich verursacht oder in ihrer Dynamik beeinflusst werden. Neue Technologien und andere Arbeitsanforderungen führen zu einem geänderten Spektrum und zur Zunahme der arbeitsbedingten Erkrankungen und Beschwerden. Während einzelne Berufskrankheiten aufgrund der Präventionsmaßnahmen seltener geworden sind, verbergen sich viele arbeitsbedingte Erkrankungen im allgemeinen Krankheitsspektrum der Bevölkerung und sind bei der hausärztlichen und klinischen Betreuung zunehmend zu berücksichtigen. Unsere "Diagnostik arbeitsbedingter Erkrankungen und arbeitsmedizinisch-diagnostische Tabellen" gehen einerseits von allgemeinen und speziellen Krankheitsbildern aus und geben eine Übersicht über die möglichen Ursachen. Andererseits werden bestimmte Gefährdungen und die möglichen Beschwerden und Erkrankungen aufgeführt. Bei ausgewählten Erkrankungen werden Hinweise zur spezifischen Diagnostik und Differentialdiagnostik gegeben. Die Darstellungen orientieren sich daher auch am allgemeinen Krankheitsspektrum und sind nicht nur auf die anerkannten Berufskrankheiten eingeengt. Unsere Ausführungen und Tabellen, die in Kooperation mit den jeweiligen Fachvertretern der Medizinischen Fakultät in Homburg erarbeitet wurden, umfassen arbeitsbedingte Atemwegs- und Lungenkrankheiten, Herz- und Kreislaufkrankheiten, Karzinome, Leberkrankheiten, neurologische Krankheiten, Nieren- und Harnwegserkrankungen, ophthalmologische Krankheiten, orthopädisch-chirurgische Erkrankungen der Bewegungsorgane, sensibilisierende Arbeitsstoffe, Virus- und Infektionskrankheiten und verschiedene aktuelle Kurzinformationen. Aufgrund unserer besonderen poliklinischen Tätigkeit haben wir über Jahrzehnte Informationen über arbeitsbedingte Erkrankungen gesammelt und im Jahr 2000 in einer ersten Form zusammen gestellt und im Internet veröffentlicht. Die jetzige Fassung 2007 gehört längst zur Pflichtlektüre für unsere Studierenden und für die Facharztweiterbildung. Die Aktualisierung und Ergänzung ist laufend vorgesehen

An extended association screen in multiple sclerosis using 202 microsatellite markers targeting apoptosis-related genes does not reveal new predisposing factors

Apoptosis, the programmed death of cells, plays a distinct role in the etiopathogenesis of Multiple sclerosis (MS), a common disease of the central nervous system with complex genetic background. Yet, it is not clear whether the impact of apoptosis is due to altered apoptotic behaviour caused by variations of apoptosis-related genes. Instead, apoptosis in MS may also represent a secondary response to cellular stress during acute inflammation in the central nervous system. Here, we screened 202 apoptosis-related genes for association by genotyping 202 microsatellite markers in initially 160 MS patients and 160 controls, both divided in 4 sets of pooled DNA samples, respectively. When applying Bonferroni correction, no significant differences in allele frequencies were detected between MS patients and controls. Nevertheless, we chose 7 markers for retyping in individual DNA samples, thereby eliminating 6 markers from the list of candidates. The remaining candidate, the ERBB3 gene microsatellite, was genotyped in additional 245 MS patients and controls. No association of the ERBB3 marker with the disease was detected in these additional cohorts. In consequence, we did not find further evidence for apoptosis-related genes as predisposition factors in MS

Cannabinoids, cannabis and cannabis-based medicine for pain management: a systematic review of randomised controlled trials

ABSTRACT: Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised efficacy and adverse events (AEs) of these types of drugs for treating pain using randomised controlled trials: in people of any age, with any type of pain, and for any treatment duration. Primary outcomes were 30% and 50% reduction in pain intensity, and AEs. We assessed risk of bias of included studies, and the overall quality of evidence using GRADE. Studies of &lt;7 and &gt;7 days treatment duration were analysed separately. We included 36 studies (7217 participants) delivering cannabinoids (8 studies), cannabis (6 studies), and CBM (22 studies); all had high and/or uncertain risk of bias. Evidence of benefit was found for cannabis &lt;7 days (risk difference 0.33, 95% confidence interval 0.20-0.46; 2 trials, 231 patients, very low-quality evidence) and nabiximols &gt;7 days (risk difference 0.06, 95% confidence interval 0.01-0.12; 6 trials, 1484 patients, very low-quality evidence). No other beneficial effects were found for other types of cannabinoids, cannabis, or CBM in our primary analyses; 81% of subgroup analyses were negative. Cannabis, nabiximols, and delta-9-tetrahydrocannabinol had more AEs than control. Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain.</p

BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis

BG-12, an immunomodulatory agent, reduces frequency of new gadolinium-enhancing (Gd+) lesions in relapsing multiple sclerosis (MS). This study reports the effect of 240 mg BG-12 orally three times daily (tid) for 24 weeks on the evolution of new Gd+ lesions to T1-hypointense lesions. Brain magnetic resonance imaging (MRI) scans from patients in placebo and 240 mg BG-12 tid arms of a phase 2b study were examined retrospectively. Included patients had at least one new Gd+ lesion from weeks 4 to 12. Week 24 scans were analyzed for number and proportion of new Gd+ lesions that evolved to T1-hypointense lesions. Eighteen patients receiving BG-12 and 38 patients receiving placebo were included in the analysis. The analysis tracked 147 new Gd+ lesions in patients from the BG-12 group and 221 Gd+ lesions in patients from the placebo group. The percentage of Gd+ lesions that evolved to T1-hypointense lesions was 34% lower with BG-12 treatment versus placebo (29%, BG-12; 44%, placebo; odds ratio 0.51; 95% confidence interval 0.43, 0.61; p > 0.0001). In addition to reducing frequency of new Gd+ lesions, BG-12 significantly reduced probability of their evolution to T1-hypointense lesions in patients with MS compared with placebo