Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first disease due to disturbances in a cell organelle was discovered in 1959-62, and its basis was loose-coupling of oxidative phosphorylation in the skeletal muscle mitochondria accompanied by severe alterations of their structure (Luft's disease). During the 1980s, functional disturbances and structural alterations in the mitochondria were observed in more than 100 disease entities, mainly in parts of the central nervous system and skeletal muscles. A second breakthrough in this area was the discovery in 1963-64 that mitochondria had their own DNA, mtDNA. Following the observation in 1988 of mutations of mtDNA in mitochondrial diseases, such mutations--mainly deletions and point mutations--were observed in almost all mitochondrial diseases. A remarkable extension of the area is the notion that "normal" ageing is accompanied by decreased oxidative phosphorylation and the appearance of mtDNA mutations. During the last two years, such changes have been demonstrated in diseased states in tissues and organs, which are especially reliant on oxygen supply: in the central nervous system (Parkinson's disease, some types of epilepsy and seizures, Huntington's disease, possibly also in Alzheimer's disease); in heart muscle (cardiomyopathies) and in skeletal muscle. Type 2 diabetes or NIDDM engages two tissues most reliant on oxygen consumption, the pancreatic islets (insulin secretion) and skeletal muscle (insulin sensitivity). Both these functions are genetically determined, the latter to a high degree also controlled by "environmental" factors. The evident age factor in the development of NIDDM could be on a par with the "normal" ageing process.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Physiopathology of mitochondria. From Luft's disease to aging and diabetes]. 836 14

In October 1983, an Australian committee report on medical research involving human fetal tissue was adopted, and the transplantation of human fetal tissue into already-born patients was discussed. The propagation of fetal cells in tissue culture was carried out, but only after the death of the fetus and with the prior consent of the pregnant woman. In 1984, the French National Ethics Committee discussed the use of tissues from embryos and dead fetuses for therapeutic, scientific, and diagnostic purposes. The Council of Europe's Parliamentary Assembly adopted a recommendation in 1986 which also formulated rules for therapeutic use of tissue from dead externalized human fetuses. In the United States, research in the early 1970s investigated transplanting human tissue to alleviate Parkinson's disease and diabetes. In the wake of the debate on abortion, Congress established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral research, which investigated research involving the living fetus. The Department of Health put a moratorium on therapeutic transplants of tissue from aborted fetuses. Various issues were studied; the concepts of morality vs. immorality in Catholic medical ethics, the definition of fetus and person, fetal viability, and various definitions of fetal death (cessation of heart beat, interruption of blood circulation). The use of human fetal tissue and transplantation is governed by the Uniform Anatomical Gift Act of 1988 allowing donation provided parental consensus is reached. The ethical dilemma is whether tissues from 1.6 million abortions in the US should be discarded or used in clinical research or therapy. Justification, authorization of use, sufficiency of maternal consent, and donors benefiting from the use of fetal tissue are also examined. There is not enough information about the usefulness of human fetal tissue in contributing to high-technology medicine, yet the ethical objections are insufficient to continue a moratorium.
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PMID:The ethical use of fetal tissue for transplantation and research. 837 53

Positional cloning strategies for identification of disease genes include genetic linkage analysis in disease families and identification of individuals in whom the disease is associated with a specific chromosomal anomaly. Once a genomic region likely to contain the disease gene has been identified, overlapping genomic clones are isolated and the candidate gene sought. Somatic gene therapy entails introduction of the cloned gene into somatic cells to either replace genetically defective functions or alter pathological disease processes. Transfer of the gene may be accomplished by either DNA- or viral-mediated methods into a variety of tissue targets. Once the success and reliability of ongoing gene therapy trials for various human diseases is established, it may then be considered in the prevention and treatment of chronic, disabling diseases such as Alzheimer's disease, Parkinson's disease, arthritis, and diabetes as well as intervention of immunosenescence, when the relevant genes have been cloned. Ethical considerations for gene therapy for aging are similar to those for gene therapy in general. In addition, the ethics of gene therapy for treating diseases versus intervention of the normal aging process must be considered.
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PMID:Identification of disease genes and somatic gene therapy: an overview and prospects for the aged. 848 9

A retrospective analysis of 812 patients admitted to the Ross Tilley Burn Centre between 1984 and 1992 resulted in 37 cases of burn injuries which were directly related to premorbid disabilities. The majority of these burns (83.8 per cent) occurred in the patient's home, most commonly as scald injuries in the bath tub, the shower, or following hot water spills. Nineteen patients were male, 17 were female. The median age was 58 years. Six patients had spinal cord disorders: four had traumatic cord damage, two had spina bifida. Six patients had seizure disorders. Five of these patients had been taking anti-seizure medications, but all had subtherapeutic blood levels on admission to hospital. Two patients had diabetes mellitus with peripheral neuropathies. Thirteen patients had four miscellaneous neurological disorders, including: tardive dyskinesia (two), CVA (four), Parkinson's disease (two), Alzheimer's disease (two), cerebral palsy (one), multiple sclerosis (one) and blindness (one). Three patients had a diagnosis of syncope. Two patients had emphysema, and four were morbidly obese. The average length of stay (LOS) for the disabled patients was 27.6 days for a median burn size of 10 per cent body surface area (BSA), compared to an average LOS for the general population of 25.7 days for a larger median burn size of 21 per cent BSA. The mortality rate was also much higher in the disabled population (22.2 per cent vs. 6.0 per cent). Most of these burn injuries were preventable. A series of burn prevention guidelines is presented, in an attempt to reduce the incidence of these burn injuries in disabled patients.
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PMID:Burns in the disabled. 850 62

Oxidant stress secondary to dopamine metabolism has been proposed as a pathogenic factor in the development of Parkinson's disease. Biochemical abnormalities extending beyond the central nervous system have been identified in patients with this condition. Previous investigators have found abnormally elevated concentrations of the lipid peroxidation product, malondialdehyde, in the plasma and serum of patients with Parkinson's disease. We attempted to replicate these findings but controlled for other factors that could influence malondialdehyde levels. We detected no significant elevations in mean serum malondialdehyde concentrations in either levodopa-treated or untreated patients with Parkinson's disease, compared to normal controls; similarly, no elevation was found in a group of patients with dementia of Alzheimer's type. On the other hand, a group of subjects with diabetes mellitus but no neurodegenerative disease had significantly elevated mean serum malondialdehyde levels, consistent with previous studies of diabetic patients. Autoxidation is one of the two major routes by which dopamine and dopa metabolism may generate oxygen free radicals. We analyzed the autoxidation product of dopa, 5-S-cysteinyl-dopa, in the plasma of these same groups of patients with neurodegenerative disease and normal controls; no significant differences were identified. Serum concentrations of two other antioxidant substances, alpha-tocopherol and uric acid, were also statistically similar in these groups. In conclusion, analysis of several blood products relevant to oxidant stress, including malondialdehyde, 5-S-cysteinyl-dopa, alpha-tocopherol, and uric acid, failed to distinguish patients with Parkinson's disease or dementia of Alzheimer's type from controls.
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PMID:No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease. 855 7

Familial polyneuropathy mimicking Charcot-Marie-Tooth disease associated with parkinsonism and dementia has been reported in literature. We present with similar peroneal muscular atrophy, rigidity of upper extremities, severe peripheral neuropathy, mental retardation and diabetes mellitus. The patient, a 42-year-old man, developed progressive muscle weakness, mental retardation and difficulty in walking in childhood. Because of his pes cavus, he had three surgical operations. At the age of 20 years, he developed distal muscular atrophy of lower limbs. On neurological examination, all limb muscles were atrophic, especially in lower one third of the thigh. Rigidity was noted in the upper extremities. Deep tendon reflexes were hyperactive in the upper and diminished in the lower extremities. Muscle CT revealed low density areas in all the muscles examined, specially in the gastrocnemius and anterior tibial muscles. Needle EMG showed neurogenic change in the forearm, but not in the lower limbs, because of no voluntary contractions obtained due to severe muscle atrophy. Marked slowing of motor conduction velocity with muscle action potentials of very low amplitude was found in the ulnar nerve. Muscle action potentials were not elicited in the median and peroneal nerves. Sensory action potentials were not elicited from the median, ulnar and sural nerves. These findings were consistent with axonal polyneuropathy. In the sural nerve biopsy, the densities of myelinated fibers were markedly decreased. However, unmyelinated fiber densities were relatively preserved. Onion bulb formation was not found. This patient may be classified into hereditary motor-sensory neuropathy (HMSN) type II based on the clinical findings delayed nerve conduction velocities and axonal degeneration in the sural nerve. He has also diabetes mellitus. CT of the brain revealed nothing particular. He is one of members with familial Parkinson's disease (PD) developed in Sagamihara. Peroneal muscular atrophies are not necessarily associated with PD, though it has been occasionally complicated in various neuro-degenerative diseases including parkinsonism. We are now following the patient to detect the symptom of Parkinson's disease for early treatment.
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PMID:[An unusual case of peroneal muscular atrophy with rigidity, polyneuropathy, mental retardation, and diabetes mellitus developed in familial Parkinson's disease]. 866 30

How much vitamin E is enough? An established use of supplemental vitamin E in humans is in the prevention and therapy of deficiency symptoms. The cause of vitamin E deficiency, characterized by peripheral neuropathy and ataxia, is usually malabsorption-a result of fat malabsorption or genetic abnormalities in lipoprotein metabolism. Genetic abnormalities in the hepatic alpha-tocopherol transfer protein also cause vitamin E deficiency-defects in this protein cause an impairment in plasma vitamin E transport. Impaired delivery of vitamin E to tissues, thereby, results in deficiency symptoms. Also discussed is the use of supplemental vitamin E in chronic diseases such as ischemic heart disease, atherosclerosis, diabetes, cataracts, Parkinson's disease, Alzheimer's disease, and impared immune function, as well as in subjects receiving total parenterol nutrition. In healthy individuals, a daily intake of about 15-30 mg of alpha-tocopherol is recommended to obtain "optimal plasma alpha-tocopherol concentrations" (30 microM or greater).
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PMID:Vitamin E in humans: demand and delivery. 883 30

From October 1995 until April 1996. CABG (coronary artery bypass grafting) was performed under the beating heart without CPB (cardiopulmonary bypass) in nine cases. They consisted of 7 males and 2 females ranging in age from 31 to 79 years old (mean 64.7 years). Single bypass grafting was performed in 6 cases, and double bypass grafting was done in 3 cases, involving 2 re-do cases. With regard to the major associated diseases, two patients had required chronic hemodialysis three time a week, four patients were administered with insulin for diabetes mellitus. There were other three patients with renal dysfunction not requiring hemodialysis, two patients had pulmonary problems, and one patient had Parkinson's disease. Further more two patients were older than 75th years in age. Graft anastomosis to the coronary artery was performed with 7-0 polypropylene. In one case, left thoracotomy was done to approach the heart for the anastomosis to intermediate artery, and in the other eight cases, median sternotomy was done. The grafts used in the nine cases were 4 right internal thoracic arteries, 6 left internal thoracic arteries, one gastroepiploic artery and one saphenous vein, 12 grafts in total. Subtotal gastrectomy for gastric cancer and cholecystectomy for cholecystitis was done in one patient for each. Heterologous blood transfusion was required two cases (22.2%). The postoperative course was very good in all cases. Eleven grafts in postoperative angiographed 8 cases were all patent, although presenting the string sign in one case, and angina pectoris disappeared in all cases. CABG under the beating heart without CPB was considered to be useful for the patients with considerable other diseases from the point of view of safety and ease of postoperative managements. We think that this procedure should be considered particularly for patients on chronic hemodialysis who required CABG.
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PMID:[Coronary artery bypass grafting without cardiopulmonary bypass]. 907 Nov 30

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications. Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e.g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e.g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson's disease treatment-related psychosis]. In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson's disease. Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.
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PMID:Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. 911 22

Drug-induced parkinsonism (DIP) is frequent. The list of drugs able to induce parkinsonism is long and probably incomplete, because new drugs, with previously unknown antidopaminergic activity, are constantly being added. Not all the drugs have the same potency for inducing parkinsonism. We classify these drugs in three groups: (1) drugs with obvious antidopaminergic activity which regularly induce parkinsonism; (2) drugs able to induce parkinsonism in particular individuals and (3) drugs which may aggravate Parkinson's disease treated with levodopa. The reports of isolated cases of parkinsonism induced by widely-used drugs (drugs in group 2) may be the result of either an idiosyncratic side effect or a misdiagnosis of parkinsonism. The antidopaminergic activity of the drugs of this group is weak and not sufficiently demonstrated. Maybe, in these cases, the blockage of other neurotransmitters different from dopamine plays a role in the induction of parkinsonism. Probably, the number of patients with DIP is higher than reported or detected, because many patients suffer from weak symptoms that quickly disappear after drug withdrawal. One of the main points of interest is knowing the list, because all these drugs, specially those of group 1, should be avoided or used with caution in the treatment of some common symptomatic problems in patients with Parkinson's disease, such as depression, arterial hypertension, diabetes mellitus and cardiac disorders. The precautions should extent to other populations especially susceptible to suffer from DIP, such as the elderly or patients with other neurodegenerative disorders, such as Alzheimer's disease.
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PMID:Drugs inducing or aggravating parkinsonism: a review. 913 99


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