Propofol beyond use dating
The discovery of MPTP‐induced parkinsonism lends further weight to this theory.59 A rural environment has been associated with an increased risk of developing Parkinson’s disease, suggesting that agents such as herbicides or pesticides may have an aetiological role, although this is limited to approximately 10% of patients with Parkinson’s disease.115 Cigarette smoking has been shown consistently to reduce the risk of developing Parkinson’s disease,3979 although this may be restricted to those with a relatively young age at onset of the disease.127 This effect has been attributed to inhibition of monoamine oxidase type B by products of tobacco combustion.Evidence linking dietary factors to Parkinson’s disease is inconclusive, although one study has shown a lower vitamin E intake in patients with Parkinson’s disease compared with controls.108Overall, most cases of Parkinson’s disease are likely to result from a combination of genetic and environmental factors and these differ between individuals.The syndrome of (clinical conditions which resemble idiopathic Parkinson’s disease) may have a number of different causes such as arteriosclerosis, diffuse central nervous system degenerative disease, repeated head trauma, tumour, metabolic defects such as Wilson’s disease, heavy metal, or carbon monoxide poisoning.Drug‐induced parkinsonism results from dopamine receptor block by drugs such as phenothiazines, butyrophenones, and metoclopramide.The lowest reported incidence is among Asians and African blacks and the highest is amongst whites.The disease was first formally described during the Industrial Revolution, suggesting that exogenous toxins may have a causative role, but descriptions of conditions resembling Parkinson’s disease are found in literature dating back thousands of years BC.
In Parkinson’s disease, the substantia nigra shows marked depletion of cells (‐acetyltranferase 2, in the pathogenesis of Parkinson’s disease have been inconclusive.5107Parkinson’s disease was first described during the industrial revolution suggesting that environmental toxins may play a role in its pathogenesis.
The observation of parkinsonian symptoms in heroin addicts who accidentally used 1‐methyl‐4‐phenyl‐1,2,5,6‐tetrahydropyridine (MPTP), a pethidine analogue, has led to the development of a useful animal model for the syndrome.59 An epidemic of encephalitis lethargica in the 1920s was responsible for an outbreak of early onset parkinsonism with associated severe rigidity and respiratory complications.
Although the aetiology of Parkinson’s disease is unknown, it has long been hypothesized that neurodegeneration is induced by genetic, environmental, or infectious disorders.
Genetic mutations may predispose patients to develop Parkinson’s disease if combined with other gene mutations or environmental factors.71 Parkinson’s disease is characterized by the progressive death of selected, but heterogeneous, populations of neurones, including those dopaminergic neurones of the pars compacta of the substantia nigra.
The precise mechanisms responsible for cell death are largely unknown and may be due to mitochondrial dysfunction, oxidative stress, the actions of excitotoxins with excess nitric oxide formation, deficient neurotrophic support, or immune mechanisms.57 Although still controversial, the final common pathway appears to be the induction of apoptosis in nigral dopaminergic neurones.1353Mitochondrial dysfunction and oxidative metabolism are major components of many current theories in Parkinson’s disease.
This highlights the difficulty of diagnosis and emphasizes that many elderly hospital patients may have undiagnosed Parkinson’s disease.