Penicillamine Neurotoxicity: An Hypothesis

Penicillamine, dimethyl cysteine, thiovaline, remains the drug of choice for the treatment of patience with Wilson disease. It is also of value in the treatment of cysteinuria and rheumatoid arthritis, it has also been suggested that it has value in the management of other rare diseases. It also has multiple toxicities. The majority of these can be explained as chemical toxicity, for instance its weak antipyridoxine action and its ability to interfere with lysyloxidea resulting in skin lesions. More important are its ability to induce immune reactions such as SLE, immune complex nephritis, the Ehlers Danlos syndrome and Goodpasture's syndrome. However the sudden increase in neurological signs which may occur in a small number of patients remains unexplained. The theory is proposed that this is due to lethal synthesis. In susceptible patients the–SH radical is liberated from penicillamine and will inhibit–SH dependent enzymes in the Krebs cycle leading to death in neurones. Other toxic metabolites may also be produced such as methyl mercaptan and ethyl mercaptan either of which could produce a similar metabolic block

How do I sound to me? Perceived changes in communication in Parkinson's disease

Objective: To examine self and carer perceived changes in communication associated with Parkinson's disease and relate these to speech intelligibility, gender, age and other disease measures. Design: Cross-sectional survey of a hospital- and community-based sample of 176 people with Parkinson's disease and their carers using a questionnaire based on semantic differential techniques. Participants: One hundred and four people with Parkinson's disease with no history of communication difficulties prior to onset of their Parkinson's disease and 45 primary carers who returned completed questionnaires. Main outcome measures: Differences in ratings for `before' the onset of Parkinson's disease versus present status. Results: There was a strong perception of negative impact on communication between `before' and `now', irrespective of age and gender and largely independent of disease severity and duration, intelligibility and cognitive status. Activities of daily living (assessed by Unified Parkinson's Disease Rating Scale (UPDRS) II) and depression rating scale scores had the strongest association with change (adjusted R 2 0.27). There was a significant correlation between the rank order of perceived change in features examined in people with Parkinson's disease versus their carers, though in general carers rated change as having less impact. Conclusions: Parkinson's disease exercises a strong influence on communication even before apparent alterations to intelligibility or motor status

New aspects of sulfur biogeochemistry during ore deposition from δ34S of elemental sulfur and organic sulfur from the Here's Your Chance Pb/Zn/Ag deposit

Sulfur isotope studies of base metal sulfide deposits have mostly focussed on sulfide minerals, but elemental sulfur and organic sulfur are also potentially significant components of the sulfur cycle during ore deposition. The δ34S of elemental sulfur and organic sulfur isolated from the Paleoproterozoic Here's Your Chance (HYC) Pb/Zn/Ag deposit (McArthur Basin, northern Australia) were measured to be between + 5 and + 8‰, approximately 6 to 7‰ heavier than the median values of first-generation HYC sulfides. Elemental sulfur and organic sulfur are thought to have been formed contemporaneously with the first generation of metal sulfides. The δ34S of organic sulfur showed an increasing trend along the path of the mineralising fluid, as sulfate was progressively 34S-enriched due to Rayleigh distillation. The δ34S data support a model in which bacterial sulfate reduction produced dissolved sulfide with δ34S of 0 to + 5‰. The subsequent oxidation of sulfide produced reactive sulfur species such as polysulfide ions, which were then incorporated into organic matter

Implementing medical revalidation in the United Kingdom: Findings about organisational changes and impacts from a survey of Responsible Officers.

Objective To describe the implementation of medical revalidation in healthcare organisations in the United Kingdom and to examine reported changes and impacts on the quality of care. Design A cross-sectional online survey gathering both quantitative and qualitative data about structures and processes for medical revalidation and wider quality management in the organisations which employ or contract with doctors (termed 'designated bodies') from the senior doctor in each organisation with statutory responsibility for medical revalidation (termed the 'Responsible Officer'). Setting United Kingdom Participants Responsible Officers in designated bodies in the United Kingdom. Five hundred and ninety-five survey invitations were sent and 374 completed surveys were returned (63%). Main outcome measures The role of Responsible Officers, the development of organisational mechanisms for quality assurance or improvement, decision-making on revalidation recommendations, impact of revalidation and mechanisms for quality assurance or improvement on clinical practice and suggested improvements to revalidation arrangements. Results Responsible Officers report that revalidation has had some impacts on the way medical performance is assured and improved, particularly strengthening appraisal and oversight of quality within organisations and having some impact on clinical practice. They suggest changes to make revalidation less 'one size fits all' and more responsive to individual, organisational and professional contexts. Conclusions Revalidation appears primarily to have improved systems for quality improvement and the management of poor performance to date. There is more to be done to ensure it produces wider benefits, particularly in relation to doctors who already perform well

Linear modeling of possible mechanisms for parkinson tremor generation

The power of Parkinson tremor is expressed in terms of possibly changed frequency response functions between relevant variables in the neuromuscular system. The derivation starts out from a linear loopless equivalent model of mechanisms for general tremor generation. Hypothetical changes in this model from the substrate of the disease are indicated, and possible ones are inferred from literature about experiments on patients. The result indicates that in these patients tremor appears to have been generated in loops, which did not include the brain area which in surgery usually is inactivated. For some patients in the literature, these loops could involve muscle length receptors, the static sensitivity of which may have been enlarged by pathological brain activity

Ocjena radne sposobnosti pacijenta s Wilsonovom bolesti - prikaz bolesnika

Wilson’s disease (WD) is a rare, progressive autosomal recessive disorder characterised by impaired transport and excessive accumulation of copper in the liver, brain, and other tissues. The disease is diagnosed based on clinical manifestations and screening tests results. Work ability assessment of patients with WD is based on the analysis of liver, kidney, neurological, and cognitive impairments, and takes into account patient’s level of education. This article presents a case with a 48-year-old male patient, who was admitted for work ability assessment due to polymorphic symptoms. The patient had been working as a salesman for 28 years. A detailed interview and examination by occupational health and other medical specialists revealed that the patient had been suffering from Wilson’s disease from the age of 13, and had now developed hepatic manifestations (compensated liver cirrhosis with portal hypertension), neurological manifestations (dystonia, dysarthria, muscle weakness, vertigo), and psychiatric manifestations (depression, insomnia, cognitive impairment) of the disease, including problems partially caused by long-lasting treatment with copper chelating agents (neurological and haematological manifestations). There were no ocular manifestations of Wilson’s disease (Kayser-Fleischer rings or sunflower cataract). The patient was assessed as having drastically diminished general work ability, dominantly due to neurological and psychiatric impairments caused by Wilson’s disease.Wilsonova je bolest rijetka, progresivna autosomno recesivna bolest karakterizirana poremećajem transporta bakra i posljedičnim prekomjernim nakupljanjem bakra u jetri, mozgu i drugim tkivima i organima. Dijagnoza bolesti postavlja se na osnovi kliničkih manifestacija bolesti i nalaza laboratorijskih ispitivanja. Ocjena radne sposobnosti pacijenata s Wilsonovom bolesti zasniva se na analizi postojanja oštećenja i stupnja oštećenja hepatičkih, neuroloških, bubrežnih i kognitivnih funkcija, kao i na analizi stupnja obrazovanja pacijenata. Prikazan je slučaj D. M., 48-godišnjeg pacijenta, koji je primljen zbog polimorfnih tegoba na bolničko ispitivanje radi ocjene radne sposobnosti. Pacijent je radio kao prodavač posljednjih 28 godina. Nakon detaljne anamneze i pregleda koje su obavili specijalisti medicine rada i drugi specijalisti utvrđeno je da pacijent boluje od Wilsonove bolesti od 13. godine života i da u ovom trenutku ima izražene hepatične manifestacije (kompenzirana ciroza jetre s portalnom hipertenzijom), neurološke manifestacije (distonija, dizartrija, mišićna slabost, vrtoglavica) i psihijatrijske manifestacije (depresija, nesanica, kognitivno oštećenje) Wilsonove bolesti, kao i da su prisutne tegobe djelomično uzrokovane dugotrajnom upotrebom kelatne terapije (neurološki i hematološki poremećaji). Nisu uočene karakteristične očne promjene Wilsonove bolesti (Kayser-Fleischerov prsten, katarakta u obliku suncokreta). Ocjenom radne sposobnosti utvrđeno je da pacijent ima drastično smanjenu radnu sposobnost pretežno zbog neuroloških i psihičkih poremećaja u sklopu Wilsonove bolesti