Occupational factors and risk of Parkinson's disease: A population-based case-control study.

BACKGROUND: Parkinson's disease (PD) has been associated with various workplace factors, but the evidence is inconsistent. OBJECTIVE: To estimate the risk of PD associated with various jobs and workplace exposures. METHODS: We conducted a population-based, case-control study of 404 incident PD cases and 526 age and sex-matched controls, collecting self-reported work histories including job titles and exposures to various industrial toxicants. Relative risks of PD from these exposures were estimated with odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. RESULTS: Risk was not significantly affected by farming work, by metal work, or by exposure to pesticides, metals, or solvents. CONCLUSIONS: These findings do not provide support for the hypothesis that workplace factors affect the risk of PD.

Dietary fats, cholesterol and iron as risk factors for Parkinson's disease.

BACKGROUND: Epidemiologic findings suggest that dietary components may contribute to the etiology of Parkinson's disease (PD). This population-based case-control study evaluated PD risk and dietary intake of fats, cholesterol and iron. METHODS: Newly diagnosed case (n=420) and age/gender/ethnicity-matched unrelated controls (n=560) were identified between 1992 and 2006 from the Group Health Cooperative health maintenance organization in western Washington State, and the University of Washington Neurology Clinic. In-person interviews elicited data on food frequency habits during most of adult life. Nutritional intakes were calculated and analyzed, with adjustments made for total energy intake (the 'nutrition density' technique). RESULTS: Cholesterol intake in the highest quartile compared with the lowest quartile was associated with a decreased risk of PD in men (odds ratio (OR)=0.53, 95%CI: 0.33, 0.86). The highest versus the lowest quartile of dietary iron increased PD risk in men (OR=1.82, 95%CI: 1.11, 2.99). When the lowest quartile of cholesterol and the highest quartile for iron were compared to the highest quartile of cholesterol and the lowest quartile of iron, no association was seen in women, but for men PD risk was increased (OR=2.70, 95%CI: 1.26, 5.76). Saturated fat intake below the median in combination with iron intake above the median also increased the PD risk (OR=1.50, 95%CI: 1.07, 2.11) in both genders combined. CONCLUSIONS: A low intake of cholesterol, particularly in the presence of high iron, may be associated with an increased risk for PD.

Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk.

Inverse associations of Parkinson's disease (PD) with cigarette smoking, coffee drinking, and nonsteroidal anti-inflammatory drug (NSAID) use have been reported individually, but their joint effects have not been examined. To quantify associations with PD for the individual, two-way and three-way combinations of these factors, a case-control association study with 1,186 PD patients and 928 controls was conducted. The study setting was the NeuroGenetics Research Consortium. Subjects completed a structured questionnaire regarding smoking, coffee, and NSAID consumption. Odds ratios were calculated using unconditional logistic regression. Smoking, coffee, and over the counter NSAID use as individual factors exhibited significantly reduced risks of 20% to 30%. The two-way and three-way combinations were associated with risk reduction of 37% to 49%, and 62%, respectively. Smoking and coffee exhibited significant inverse risk trends with increasing cumulative exposures, suggesting dose-response relations. With respect to the combination of all three exposures, persons who were at the highest exposure strata for smoking and coffee and used NSAIDs had an estimated 87% reduction in risk (OR = 0.13, 95% CI = 0.06-0.29). Whether this finding reflects true biologic protection needs to be investigated.

Diabetes, smoking, and other medical conditions in relation to Parkinson's disease risk.

Associations of Parkinson's disease (PD) with diabetes mellitus (DM) and other medical conditions were investigated in a case-control study of 352 newly diagnosed PD case and 484 control subjects. Men with DM had a significantly lower risk of PD, than men without DM (odds ratio (OR) = 0.52, 95% confidence interval (CI) = 0.28, 0.97), whereas the association in women was weaker (OR = 0.80, 95% CI = 0.35, 1.83). PD risk was reduced among male and female smokers, with and without diabetes. However, among diabetics, the PD risk was especially reduced in non-smoking men (OR = 0.09, 95% CI = 0.02, 0.44). Other medical conditions showed no strong relations with PD.

No associations between Parkinson's disease and polymorphisms of the quinone oxidoreductase (NQO1, NQO2) genes.

Reactive oxygen species derived from dopamine metabolism can induce oxidative stress and thus may contribute to Parkinson's disease (PD) pathogenesis. The quinone oxidoreductases, nicotinamide adenine dinucleotide (phosphate) (NAD[P]H): quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) detoxify quinones and quinonoid compounds. We investigated associations of genetic polymorphisms of NQO1 (C609T) and NQO2 (I/D, 29 base pairs) with PD in a population-based case-control study of 190 idiopathic PD cases and 305 unrelated controls matched on age and sex. No associations were detected for either gene variant or for any allele combinations.

Neurotoxin-induced paralysis: a case of tick paralysis in a 2-year-old child.

BACKGROUND: Tick paralysis is an arthropod-transmitted disease causing potentially lethal progressive ascending weakness. The presenting symptoms of tick paralysis overlap those of acute inflammatory diseases of the peripheral nervous system and spinal cord; thus, the condition is often misdiagnosed, leading to unnecessary treatments and prolonged hospitalization. PATIENT: A 2-year-old girl residing in northern New York and having no history of travel to areas endemic to ticks presented with rapidly progressing ascending paralysis, hyporeflexia, and intact sensory examination. Investigation included blood and serum toxicology screens, cerebrospinal fluid analysis, and brain imaging. With all tests negative, the child's condition was initially mistaken for botulism; however, an engorged tick was later found attached to the head skin. Following tick removal, the patient's weakness promptly improved with no additional interventions. CONCLUSION: Our patient illustrates the importance of thorough skin examination in all cases of acute progressive weakness and the necessity to include tick paralysis in the differential diagnosis of paralysis, even in nonendemic areas.

5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study.

The dopamine transporter gene (SLC6A3) is a candidate gene for Parkinson's disease (PD) on the basis of its critical role in dopaminergic neurotransmission. Previously, we identified 22 SNPs in the 5' region of SLC6A3, which segregate as eight haplotypes that differ in transcriptional activity when transfected in rat dopamine-producing cells. In the present work from a case-control study size of 293 cases and 395 controls, we employed a cladistic approach to examine gene-disease association. First, we found strong evidence of balancing selection in this region, as determined by a Tajima's D statistic of 2.97 (P<0.001). Second, we found that the eight haplotypes fit into two main clades and that diplotypes of these clades were marginally associated with PD. Then, after we classified cases and controls by the number of risk alleles, accounting for the well-known 3' region VNTR polymorphism, we found that having two or more risk alleles resulted in a modest but significant increase in PD risk [odds ratio=1.58; 95% confidence interval (CI): 1.03-2.40]. Finally, we detected a significant interaction between occupational pesticide exposure in men and the number of risk alleles. Among pesticide-exposed subjects, the odds ratio for having two or more risk alleles was 5.66 (95% CI: 1.73-18.53). Thus, allelic variants in SLC6A3, which affect gene expression, are associated with PD in this population and may interact with occupational pesticide exposure to increase PD risk.

Comparison of Amsorb, sodalime, and Baralyme degradation of volatile anesthetics and formation of carbon monoxide and compound a in swine in vivo.

BACKGROUND: Consequences of volatile anesthetic degradation by carbon dioxide absorbents that contain strong base include formation of compound A from sevoflurane, formation of carbon monoxide (CO) and CO toxicity from desflurane, enflurane and isoflurane, delayed inhalation induction, and increased anesthetic costs. Amsorb (Armstrong Ltd., Coleraine, Northern Ireland) is a new absorbent that does not contain strong base and does not form CO or compound A in vitro. This investigation compared Amsorb, Baralyme (Chemetron Medical Division, Allied Healthcare Products, St. Louis, MO), and sodalime effects on CO (from desflurane and isoflurane) and compound A formation, carboxyhemoglobin (COHb) concentrations, and anesthetic degradation in a clinically relevant porcine in vivo model. METHODS: Pigs were anesthetized with desflurane, isoflurane, or sevoflurane, using fresh or partially dehydrated Amsorb, Baralyme, and new and old formulations of sodalime. Anesthetic concentrations in the fresh (preabsorber), inspired (postabsorber), and end-tidal gas were measured, as were inspired CO and compound A concentrations and blood oxyhemoglobin and COHb concentrations. RESULTS: For desflurane and isoflurane, the order of inspired CO and COHb formation was dehydrated Baralyme >> soda-lime > Amsorb. For desflurane and Baralyme, peak CO was 9,700 +/- 5,100 parts per million (ppm), and the increase in COHb was 37 +/- 14%. CO and COHb increases were undetectable with Amsorb. Oxyhemoglobin desaturation occurred with desflurane and Baralyme but not Amsorb or sodalime. The gap between inspired and end-tidal desflurane and isoflurane did not differ between the various dehydrated absorbents. Neither fresh nor dehydrated Amsorb caused compound A formation from sevoflurane. In contrast, Baralyme and sodalime caused 20-40 ppm compound A. The gap between inspired and end-tidal sevoflurane did not differ between fresh absorbents, but was Amsorb < sodalime < Baralyme with dehydrated absorbents. CONCLUSION: Amsorb caused minimal if any CO formation, minimal compound A formation regardless of absorbent hydration, and the least amount of sevoflurane degradation. An absorbent like Amsorb, which does not contain strong base or cause anesthetic degradation and formation of toxic products, may have benefit with respect to patient safety, inhalation induction, and anesthetic consumption (cost).

Chronic cocaine exposure alters carbon dioxide reactivity but does not affect cerebral blood flow autoregulation in anesthetized dogs.

BACKGROUND: Cocaine use is common in trauma victims. Consequently, understanding how cocaine alters normal physiology is important to providing appropriate medical care for these patients. This study was designed to identify how chronic cocaine exposure alters cerebrovascular physiology. METHODS: Ten dogs (seven experimental, three control) were studied. Transcranial Doppler was used to measure CO2 reactivity and autoregulation of cerebral blood flow velocity (CBFvel). Measurements were made in anesthetized animals (0.6% or 1.8% isoflurane in oxygen and intravenous fentanyl) at baseline before cocaine exposure and then at weekly intervals for 4 weeks. During the 4-week study period, cocaine was administered intravenously four times per day. RESULTS: Cocaine did not alter autoregulation of CBFvel in response to changes in mean arterial pressure. However, cocaine markedly impaired CO2 reactivity in three of the seven animals. In this subset of animals, increasing Paco2 decreased CBFvel, which is consistent with vasoconstriction rather than vasodilation. CONCLUSION: Chronic cocaine exposure does not alter autoregulation of CBFvel but does alter CO2 reactivity in a subset of susceptible animals. If confirmed in humans, these findings have implications for traumatic brain injury patients who are chronic cocaine users. Specifically, the findings suggest that hyperventilation could exacerbate intracranial hypertension in a subset of these patients.