An impairment in sniffing contributes to the olfactory impairment in Parkinson's disease

Although the presence of an olfactory impairment in Parkinson's disease (PD) has been recognized for 25 years, its cause remains unclear. Here we suggest a contributing factor to this impairment, namely, that PD impairs active sniffing of odorants. We tested 10 men and 10 women with clinically typical PD, and 20 age- and gender-matched healthy controls, in four olfactory tasks: (i) the University of Pennsylvania smell identification test; (ii and iii) detection threshold tests for the odorants vanillin and propionic acid; and (iv) a two-alternative forced-choice detection paradigm during which sniff parameters (airflow peak rate, mean rate, volume, and duration) were recorded with a pneomatotachograph-coupled spirometer. An additional experiment tested the effect of intentionally increasing sniff vigor on olfactory performance in 20 additional patients. PD patients were significantly impaired in olfactory identification (P < 0.0001) and detection (P < 0.007). As predicted, PD patients were also significantly impaired at sniffing, demonstrating significantly reduced sniff airflow rate (P < 0.01) and volume (P < 0.002). Furthermore, a patient's ability to sniff predicted his or her performance on olfactory tasks, i.e., the more poorly patients sniffed, the worse their performance on olfaction tests (P < 0.009). Finally, increasing sniff vigor improved olfactory performance in those patients whose baseline performance had been poorest (P < 0.05). These findings implicate a sniffing impairment as a component of the olfactory impairment in PD and further depict sniffing as an important component of human olfaction

Solvent exposures and parkinson disease risk in twins

Objective: Several case reports have linked solvent exposure to Parkinson disease (PD), but few studies have assessed associations with specific agents using an analytic epidemiologic design. We tested the hypothesis that exposure to specific solvents is associated with PD risk using a discordant twin pair design. Methods: Ninety‐nine twin pairs discordant for PD ascertained from the National Academy of Sciences/National Research Council World War II Veteran Twins Cohort were interviewed regarding lifetime occupations and hobbies using detailed job task–specific questionnaires. Exposures to 6 specific solvents selected a priori were estimated by expert raters unaware of case status. Results: Ever exposure to trichloroethylene (TCE) was associated with significantly increased risk of PD (odds ratio [OR], 6.1; 95% confidence interval [CI] 1.2–33; p = 0.034), and exposure to perchloroethylene (PERC) and carbon tetrachloride (CCl 4 ) tended toward significance (respectively: OR, 10.5; 95% CI, 0.97–113; p = 0.053; OR, 2.3; 95% CI, 0.9–6.1; p = 0.088). Results were similar for estimates of exposure duration and cumulative lifetime exposure. Interpretation: Exposure to specific solvents may increase risk of PD. TCE is the most common organic contaminant in groundwater, and PERC and CCl 4 are also ubiquitous in the environment. Our findings require replication in other populations with well‐characterized exposures, but the potential public health implications are substantial. ANN NEUROL 2011Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92108/1/22629_ftp.pd

Mitochondria and Energetic Depression in Cell Pathophysiology

Mitochondrial dysfunction is a hallmark of almost all diseases. Acquired or inherited mutations of the mitochondrial genome DNA may give rise to mitochondrial diseases. Another class of disorders, in which mitochondrial impairments are initiated by extramitochondrial factors, includes neurodegenerative diseases and syndromes resulting from typical pathological processes, such as hypoxia/ischemia, inflammation, intoxications, and carcinogenesis. Both classes of diseases lead to cellular energetic depression (CED), which is characterized by decreased cytosolic phosphorylation potential that suppresses the cell’s ability to do work and control the intracellular Ca2+ homeostasis and its redox state. If progressing, CED leads to cell death, whose type is linked to the functional status of the mitochondria. In the case of limited deterioration, when some amounts of ATP can still be generated due to oxidative phosphorylation (OXPHOS), mitochondria launch the apoptotic cell death program by release of cytochrome c. Following pronounced CED, cytoplasmic ATP levels fall below the thresholds required for processing the ATP-dependent apoptotic cascade and the cell dies from necrosis. Both types of death can be grouped together as a mitochondrial cell death (MCD). However, there exist multiple adaptive reactions aimed at protecting cells against CED. In this context, a metabolic shift characterized by suppression of OXPHOS combined with activation of aerobic glycolysis as the main pathway for ATP synthesis (Warburg effect) is of central importance. Whereas this type of adaptation is sufficiently effective to avoid CED and to control the cellular redox state, thereby ensuring the cell survival, it also favors the avoidance of apoptotic cell death. This scenario may underlie uncontrolled cellular proliferation and growth, eventually resulting in carcinogenesis

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Oncology education programs in a community hospital : an interprofessional approach

Includes bibliographical references (pages 29-31)During the past twenty-five years, the role of chemotherapy in the treatment of cancer patients has evolved from one of palliation for the patient with disseminated metastases to one of potentially curative treatment for the patient with early disease. The use of these drugs has now become standard practice. In order to insure that maximum benefit is derived from a given treatment program, it is essential that each member of the health care team be cognizant of both the toxic manifestations and beneficial effects of these complex agents.\ud The purpose of this study was to describe how an interprofessional approach was used in:\ud 1. Identifying the problems which resulted in a significantly increased number of medication errors and an excessive incidence of toxic responses to chemotherapy treatment programs in a community hospital.\ud 2. Developing continuing education programs to correct the problems thus identified.\ud 3. Evaluating the effectiveness of these programs.\ud Behavior-oriented outcome statements were formulated for each of the model programs. Data was collected from patient charts, the professional staff and the patients themselves in a pre and post situation analysis to determine whether the expected outcomes had in fact occurred. Feedback from these sources indicated that the desired behavior changes had occurred.\ud The materials developed as a result of this study were made available to the Hospital Pharmacy to allow them to continue to offer and expand the program

Voluntarily simulated tremor in normal subjects

Based on the hypothesis that rhythmical, tremor-like movements produced by normal subjects might be influenced by similar central oscillatory neuronal networks believed to determine the features of the pathologic tremors of Parkinson's disease (PD) or Essential Tremor (ET) patients, we examined the neurophysiological characteristics of a tremor mimicked by normal volunteers and compare this data with those from PD or ET tremors. Voluntarily simulated tremor (VST) was studied in 47 neurologically intact subjects, resting tremor in 10 patients with PD and postural tremor in 10 patients with ET. Using a tremor analysis system based on a solid state gyroscopic sensor sensitive to angular rate, the following parameters were determined: frequency, amplitude (angular displacement) and regularity (Q coefficient of constancy). We also performed an inertial loading test and a test-retest analysis. Nearly all normal subjects were able to simulate a tremor that was indistinguishable, in frequency and regularity, from that of PD or ET, although the amplitude was significantly higher in normal subjects. As in pathological tremors, the VST frequency was significantly influenced by age, but not by gender, handedness or previous knowledge of tremor. Inertial load did not modify the tremor frequency, suggesting that mechanical factors were minor. We also found a logarithmic inverse relationship between frequency and amplitude of the VST. We concluded that VST shares many similarities with pathological tremors. It is therefore possible that all tremors are somehow influenced by the same central oscillators which may become disinhibited and clinically apparent in pathological conditions such as PD or ET

MPTP-induced parkinsonism: an historical case series

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