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Gradual Decline (gradual + decline)
Selected AbstractsNormal Values of Balance Tests in Women Aged 20,80JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2004Rosemary C. Isles B Phty Objectives: To determine normal values for four commonly used clinical functional balance tests from community-dwelling women aged 20 to 80 and to identify any significant decline due to aging. Design: A cross-sectional study was undertaken to provide normative values for four clinical balance tests across 6 decade cohorts. Setting: The Betty Byrne-Henderson Center for Women and Aging, Royal Womens' Hospital, Brisbane, Australia. Participants: Four hundred fifty-six community-dwelling, independently ambulant women with no obvious neurological or musculoskeletal-related disability, aged 20 to 80, were randomly recruited from a large metropolitan region. Measurements: The clinical balance measures/tests were the Timed Up and Go test, step test, Functional Reach test, and lateral reach test. Multivariate analysis was used to test the effect for age, height, and activity level. Results: Normal data were produced for each test across each decade cohort. Gradual decline in balance performance was confirmed, with significant effect for age demonstrated. Conclusion: New normative data across the adult age decades are available for these clinical tests. Use of clinical balance tests could complement other balance tests and be used to screen women aged 40 to 60 whose performance is outside the normal values for age and to decrease later falls risk. [source] Postglacial topographic evolution of glaciated valleys: a stochastic landscape evolution modelEARTH SURFACE PROCESSES AND LANDFORMS, Issue 11 2005Simon J. Dadson Abstract The retreat of valley glaciers has a dramatic effect on the stability of glaciated valleys and exerts a prolonged influence on the subsequent fluvial sediment transport regime. We have studied the evolution of an idealized glaciated valley during the period following retreat of ice using a numerical model. The model incorporates a stochastic process to represent deep-seated landsliding, non-linear diffusion to represent shallow landsliding and an approximation of the Bagnold relation to represent fluvial sediment transport. It was calibrated using field data from several recent surveys within British Columbia, Canada. We present ensemble model results and compare them with results from a deterministic linear-diffusion model to show that explicit representation of large landslides is necessary to reproduce the morphology and channel network structure of a typical postglacial valley. Our model predicts a rapid rate of fluvial sediment transport following deglaciation with a subsequent gradual decline, similar to that inferred for Holocene time. We also describe how changes in the model parameters affect the estimated magnitude and duration of the paraglacial sediment pulse. Copyright © 2005 John Wiley & Sons, Ltd. [source] Recent evolution of the fishing exploitation in the Thau lagoon, FranceFISHERIES MANAGEMENT & ECOLOGY, Issue 1 2002V. CRESPI Fisheries activity in the Thau marine lagoon (Mediterranean coast of France) has an old tradition and involves different types of gears (set nets, traps and lines) that are used seasonally with varying frequencies in different areas. A survey of fishing activity, main fishing methods and main commercial species composition in the lagoon was carried out to assess the current fishing effort and seasonal yield. Many important changes in fishing effort and in the most important target species occurred during the last 10 years. A gradual decline in eel, Anguilla anguilla (L.), catches followed by an increase of other commercially-exploited species, particularly the gilthead sea-bream, Sparus aurata L., was observed. [source] Effects of ultraviolet radiation on the eggs of landlocked Galaxias maculatus (Galaxiidae, Pisces) in northwestern PatagoniaFRESHWATER BIOLOGY, Issue 3 2000M. Battini Summary 1Ultraviolet radiation (UVR) damages early life stages of several fish species. Galaxias maculatus is a small catadromous fish, with landlocked forms occurring in many lakes within the Nahuel Huapi National Park (Patagonia, Argentina). In this work, the vulnerability of G. maculatus eggs exposed to both natural and artificial UVR was investigated in relation to water transparency. 2Field experiments were performed in two lakes differing in UVR attenuation. Galaxias maculatus eggs were exposed to in situ levels of UVR in quartz tubes incubated at various depths. For laboratory experiments, the eggs were exposed to five levels of artificial UVB radiation. 3Exposure to natural UVR causes various degrees of egg mortality depending on water transparency and incubation depth. In the less transparent lake (Kd320 = 3.08 m -1), almost complete mortality was observed near the surface. At a depth of 43 cm the observed mortality was only 22%, but was still significantly different from the dark control. In the most transparent lake (Kd320 = 0.438 m -1), almost total mortality was observed in tubes incubated at 2.56 m or shallower. A gradual decline in mortality was recorded from that depth to 3.78 m where the values approached those in the dark control treatments. 4A monotonic relationship between mortality and UV exposure could be observed both in field and laboratory experiments. Using the results from field incubations, a LD50 of 2.5 J cm -2 nm -1 was estimated. In a few mountain lakes, this value would be exceeded even if the eggs were laid at the maximum depth of the lake. Thus UVR seems a sufficient cause to explain the absence of G. maculatus populations in some mountain lakes. For most lakes, however, UVR is probably one of several important environmental factors, which together determine the habitat suitability. [source] A prospective baseline study of frail older people before the introduction of an intermediate care serviceHEALTH & SOCIAL CARE IN THE COMMUNITY, Issue 4 2005John Young MB MSC FRCP Abstract This paper describes the first part of a two-stage research project designed to investigate the clinical and service outcomes of a comprehensive intermediate care service. It is a baseline study of patients presenting to two elderly care departments as emergencies with the clinical syndromes of falls, incontinence, confusion or poor mobility before the introduction of a city-wide intermediate care service. The outcome measures were: mortality; disability (Barthel Index, BI); social activities (Nottingham Extended Activities of Daily Living); service use; and carer distress (General Health Questionnaire ,28). These were measured at 3, 6 and 12 months after recruitment. Eight hundred and twenty-three patients were recruited (median age = 84 years; proportion of women = 70%; proportion with cognitive impairment = 45%; median BI score = 15). There was a high mortality rate (36%), evidence for incomplete recovery, a gradual decline in independence over 12 months and a high degree of carer stress. There was little use of rehabilitation services (< 5%), about 25% required readmission to hospital by each assessment point and there was a gradual increase in institutional care admissions. These findings support a needs-based argument for a more comprehensive community service for frail older people. [source] Antibodies Against Hepatitis C Virus,Like Particles and Viral Clearance in Acute and Chronic Hepatitis CHEPATOLOGY, Issue 3 2000Thomas F. Baumert M.D. We recently described the efficient assembly of hepatitis C virus (HCV) structural proteins into HCV-like particles (HCV-LPs) in insect cells. These noninfectious HCV-LPs have similar morphologic and biophysical properties as putative virions isolated from HCV-infected humans and can induce a broadly directed immune response in animal models. The HCV envelope proteins of HCV-LPs are presumably presented in a native, virion-like conformation and may therefore interact with antienvelope antibodies directed against conformational epitopes. In this study, HCV-LPs were used as capture antigens in an enzyme-linked immunosorbent assay (ELISA) to detect and quantify antibodies against HCV structural proteins in patients with acute and chronic hepatitis C. High titers of anti,HCV-LP antibodies were detected in patients chronically infected with HCV genotypes 1 to 6. In contrast to individuals with chronic hepatitis C, patients with acute self-limited hepatitis C displayed only a transient and weak seroreactivity against HCV-LPs. Patients with chronic HCV infection successfully treated with interferon demonstrated a gradual decline of anti,HCV-LP titers during or subsequent to viral clearance. Sustained interferon responders were characterized by significantly higher pretreatment levels of anti,HCV-LP antibodies as compared with nonresponders (P = .0001). In conclusion, HCV infection is associated with limited humoral immunity against the envelope proteins present on the HCV-LPs. An HCV-LP,based ELISA may be a useful diagnostic tool to distinguish acute hepatitis C from chronic HCV infection with exacerbation, and to predict viral clearance in response to interferon. [source] Australian Universities 1939-1999: How Different Now?HIGHER EDUCATION QUARTERLY, Issue 2 2000Bruce Williams Between 1939 and 1999, when the Australian population increased from 7 to 19 million, university enrolments rose from 14,236 to 681,870. Until 1974 the most notable changes were the increases in the size of universities and of departments (which encouraged greater specialization), continued increases in research expenditures, in the percentage of postgraduate students, and a gradual decline in collegiality. In 1974 the Commonwealth Government assumed full responsibility for government grants to universities and abolished fees at just that time when growth rates in the economy fell sharply. Government influence on the universities increased, and there were some departures from the no-fees policy for international and postgraduate course-work masters and diploma students. Then in 1988 the Government decided to abolish the distinction between universities and colleges of advanced education, to create through amalgamations a smaller number of much larger universities and to set a specific mission for each university in the interest of economic growth. The Tertiary Education Commission was abolished and the universities dealt directly with the Minister and his Department. The Universities became distinctly more managerial, less collegial, and the range of courses and degrees was greatly expanded. There are now legitimate doubts about the quality of some degrees. Student fees came back, but in a way that reduced the financial burden on the government without giving the universities greater freedom. The government sponsored collective bargaining for university staff but as universities were not given the capacity to earn much additional income, increases in salaries increased student/staff ratios and induced a decline in morale. [source] Air temperatures at Armagh Observatory, Northern Ireland, from 1796 to 2002INTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 8 2005C. J. Butler Abstract Three independent mean temperature series for Armagh Observatory, covering the period 1796,2002 have been calibrated and corrected for the time of reading and exposure. Agreement between the three series is good in regions of overlap. With a short gap in the Armagh data from 1825 to 1833 filled by data from two stations in Dublin, the resulting series is the longest for the island of Ireland and one of the longest for any single site in the British Isles. Over the past 207 years, we note that temperatures in Armagh, in all seasons, show a gradual overall trend upwards. However, there are seasonal differences: summer and spring temperatures have increased by only half as much as those in autumn and winter. This is partly due to the exceptionally cold winters and autumns experienced prior to 1820. Relative to the overall trend, warm periods occurred in Ireland, as in other parts of Europe, in the mid-19th century, in the mid-20th century and at the end of the 20th century. Relatively cool temperatures prevailed in the early 19th century, in the 1880s and in the 1970s. Thus, if the baseline against which current temperatures are compared were moved from the late 19th century to include the earlier warm period, the apparent warming at the end of the late 20th century would be correspondingly reduced. A gradual decline in the daily temperature range at Armagh since 1844 may have resulted from higher minimum temperatures associated with increased cloudiness. A 7.8 year periodicity is identified in winter and spring mean temperatures at Armagh, which is probably a consequence of the North Atlantic oscillation. Copyright © 2005 Royal Meteorological Society [source] Leaf Decomposition in a Mountain Stream in the Sultanate of OmanINTERNATIONAL REVIEW OF HYDROBIOLOGY, Issue 1 2009Maha Al-Riyami Abstract Decomposition of Juglans regia leaves was studied in fine and coarse mesh bags in a permanent mountain stream in Oman. A rapid initial mass loss, attributed to leaching, was followed by a more gradual decline. Daily exponential decay rates (k) calculated over 32 days were 0.011 (fine mesh litter bags) and 0.014 (coarse mesh litter bags). The difference between bag types was not significant, suggesting limited impact of leaf-shredding invertebrates. Ergosterol levels on leaves from fine mesh bags peaked at 0.3 mg g,1 AFDM after 16 days of stream exposure. During the experimental period, which followed the annual leaf fall, the concentration of aquatic hyphomycete conidia in the stream varied between 82 and 1362 l,1. Based on the morphology of conidia found in the water column or released from leaves, we identified 14 species of aquatic hyphomycetes. Tetracladium apiense was the most common taxon (62.2% of conidia in water column during the field experiment). Three other Tetracladium species contributed another 8%. Plating out leaf particles yielded common epiphytic taxa such as Alternaria sp., Aureobasidium pullulans and Phoma sp. The measured metrics of leaf decay in this desert stream fall within the range of values observed in temperate and tropical streams, with clear evidence for an early leaching phase, and no evidence of a strong impact of leaf shredders. The community of aquatic hyphomycetes appears impoverished. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Persistence of Pulmonary Vein Isolation After Robotic Remote-Navigated Ablation for Atrial Fibrillation and its Relation to Clinical OutcomeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2010STEPHAN WILLEMS M.D. Robotic Remote Ablation for AF. Aims: A robotic navigation system (RNS, HansenÔ) has been developed as an alternative method of performing ablation for atrial fibrillation (AF). Despite the growing application of RNS-guided pulmonary vein isolation (PVI), its consequences and mechanisms of subsequent AF recurrences are unknown. We investigated the acute procedural success and persistence of PVI over time after robotic PVI and its relation to clinical outcome. Methods and Results: Sixty-four patients (60.7 ± 9.8 years, 53 male) with paroxysmal AF underwent robotic circumferential PVI with 3-dimensional left atrial reconstruction (NavXÔ). A voluntary repeat invasive electrophysiological study was performed 3 months after ablation irrespective of clinical course. Robotic PVI was successful in all patients without complication (fluoroscopy time: 23.5 [12,34], procedure time: 180 [150,225] minutes). Fluoroscopy time demonstrated a gradual decline but was significantly reduced after the 30th patient following the introduction of additional navigation software (34 [29,45] vs 12 [9,17] minutes; P < 0.001). A repeat study at 3 months was performed in 63% of patients and revealed electrical conduction recovery in 43% of all PVs. Restudied patients without AF recurrence (n = 28) showed a significantly lower number of recovered PVs (1 (0,2) vs 2 (2,3); P = 0.006) and a longer LA-PV conduction delay than patients with AF recurrences (n = 12). Persistent block of all PVs was associated with freedom from AF in all patients. At 3 months, 67% of patients were free of AF, while reablation of recovered PVs led to an overall freedom from AF in 81% of patients after 1 year. Conclusion: Robotic PVI for PAF is safe, effective, and requires limited fluoroscopy while yielding comparable success rates to conventional ablation approaches with PV reconduction as a common phenomenon associated with AF recurrences. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1079-1084) [source] Time Course of Elevated Ethanol Intake in Adolescent Relative to Adult Rats Under Continuous, Voluntary-Access ConditionsALCOHOLISM, Issue 7 2007Courtney S. Vetter Background: Adolescence is a period of elevated alcohol consumption in humans as well as in animal models. Previous studies in our laboratory have shown that adolescent Sprague,Dawley rats consume approximately 2 times more ethanol on a gram per kilogram basis than adult animals in a 2-bottle choice free-access situation. The purpose of the present study was to examine the time course and pattern of elevated ethanol intake during adolescence and the adolescent-to-adult transition, contrast this intake with ontogenetic patterns of food and water intake, and determine whether adolescent access to ethanol elevates voluntary consumption of ethanol in adulthood. Methods: Adolescent [postnatal day (P)27,28] and adult (P69,70) male Sprague,Dawley rats were singly housed with continuous access to both water and 1 of 3 experimental solutions in ball-bearing,containing sipper tubes: unsweetened ethanol (10% v/v), sweetened ethanol (10% v/v+0.1% w/v saccharin), and saccharin alone (0.1% w/v). Results: Ethanol consumption plateaued at approximately 7.5 g/kg/d during the first 2 weeks of measurement (i.e., P28,39) in early adolescence, before declining sharply at approximately P40 to levels that were only modestly elevated compared with adult-typical consumption patterns that were reached by approximately P70. In contrast, intake of food and total calories showed a more gradual decline into adulthood with no distinguishable plateaus in early adolescence. When adolescent-initiated and adult-initiated animals were tested at the same chronological age in adulthood, animals drank similar amounts regardless of the age at which they were first given voluntary access to ethanol. Conclusions: Taken together, these data suggest that the elevated ethanol intake characteristic of early-to-mid adolescence is not simply a function of adolescent-typical hyperphagia or hyperdipsia, but instead may reflect age-related differences in neural substrates contributing to the rewarding or aversive effects of ethanol, as well as possible modulatory influences of ontogenetic differences in sensitivity to novelty or in ethanol pharmacokinetics. Voluntary home cage consumption of ethanol during adolescence, however, was not found to subsequently elevate ethanol drinking in adulthood. [source] The Sociopolitical Status of U.S. Naturopathy at the Dawn of the 21st CenturyMEDICAL ANTHROPOLOGY QUARTERLY, Issue 3 2001Hans A. Baer Naturopathic medicine in the United States had its inception around the turn of the 20th century. Subsequently, it underwent a process of relatively rapid growth until around the 1930s, followed by a period of gradual decline almost to the point of extinction due to biomedical opposition and the advent of "miracle drugs." Because its therapeutic eclecticism had preadapted it to fit into the holistic health movement that emerged in the 1970s, it was able to undergo a process of organizational rejuvenation during the last two decades of the century. Nevertheless, U.S. naturopathy as a professionalized heterodox medical system faces several dilemmas as it enters the new millennium. These include (1) the fact that it has succeeded in obtaining licensure in only two sections of the country, namely, the Far West and New England; (2) increasing competition from partially professionalized and lay naturopaths, many of whom are graduates of correspondence schools; and (3) the danger of cooptation as many biomedical practitioners adopt natural therapies, [naturopathy, alternative medicine, medical pluralism] [source] The decline of a regional fishing nation: The case of Ghana and West AfricaNATURAL RESOURCES FORUM, Issue 1 2004John Atta-Mills Abstract Inadequate trade policies, globalization of the fishing industry, dominance of Europe's distant water fleets, declarations of exclusive economic zones (EEZs) by neighbouring West African nations, overfishing and a lack of good governance contributed to the decline of Ghana as a regional fishing nation, a position it had held since the 18th century. The prohibitive cost of access arrangements limited Ghana's access to distant waters. The country's marine environments have been impacted by overexploitation of stocks and the use of destructive methods. Subsistence fishing has become the sole means of survival for many fishers. The decline of the fishing sector has limited the country's ability to meet domestic demand and threatened the economic and food security of many Ghanaians. The article traces the early history of Ghana's fisheries, their gradual decline during the last four decades, and outlines recommendations for policy changes to address the situation and steer the nation on a course towards sustainable fisheries. [source] Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)PAIN PRACTICE, Issue 4 2008Joseph Pergolizzi MD ,,Abstract Summary of consensus: 1.,The use of opioids in cancer pain:, The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities,including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia,and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation,fentanyl and buprenorphine,fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2.,The use of opioids in noncancer-related pain:, Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying guidelines in clinical practice. 3.,The use of opioids in neuropathic pain:, The role of opioids in neuropathic pain has been under debate in the past but is nowadays more and more accepted; however, higher opioid doses are often needed for neuropathic pain than for nociceptive pain. Most of the treatment data are level II or III, and suggest that incorporation of opioids earlier on might be beneficial. Buprenorphine shows a distinct benefit in improving neuropathic pain symptoms, which is considered a result of its specific pharmacological profile. 4.,The use of opioids in elderly patients with impaired hepatic and renal function:, Functional impairment of excretory organs is common in the elderly, especially with respect to renal function. For all opioids except buprenorphine, half-life of the active drug and metabolites is increased in the elderly and in patients with renal dysfunction. It is, therefore, recommended that,except for buprenorphine,doses be reduced, a longer time interval be used between doses, and creatinine clearance be monitored. Thus, buprenorphine appears to be the top-line choice for opioid treatment in the elderly. 5.,Opioids and respiratory depression:, Respiratory depression is a significant threat for opioid-treated patients with underlying pulmonary condition or receiving concomitant central nervous system (CNS) drugs associated with hypoventilation. Not all opioids show equal effects on respiratory depression: buprenorphine is the only opioid demonstrating a ceiling for respiratory depression when used without other CNS depressants. The different features of opioids regarding respiratory effects should be considered when treating patients at risk for respiratory problems, therefore careful dosing must be maintained. 6.,Opioids and immunosuppression:, Age is related to a gradual decline in the immune system: immunosenescence, which is associated with increased morbidity and mortality from infectious diseases, autoimmune diseases, and cancer, and decreased efficacy of immunotherapy, such as vaccination. The clinical relevance of the immunosuppressant effects of opioids in the elderly is not fully understood, and pain itself may also cause immunosuppression. Providing adequate analgesia can be achieved without significant adverse events, opioids with minimal immunosuppressive characteristics should be used in the elderly. The immunosuppressive effects of most opioids are poorly described and this is one of the problems in assessing true effect of the opioid spectrum, but there is some indication that higher doses of opioids correlate with increased immunosuppressant effects. Taking into consideration all the very limited available evidence from preclinical and clinical work, buprenorphine can be recommended, while morphine and fentanyl cannot. 7.,Safety and tolerability profile of opioids:, The adverse event profile varies greatly between opioids. As the consequences of adverse events in the elderly can be serious, agents should be used that have a good tolerability profile (especially regarding CNS and gastrointestinal effects) and that are as safe as possible in overdose especially regarding effects on respiration. Slow dose titration helps to reduce the incidence of typical initial adverse events such as nausea and vomiting. Sustained release preparations, including transdermal formulations, increase patient compliance.,, [source] Perspectives on the Recent Decline in Disability at Older AgesTHE MILBANK QUARTERLY, Issue 3 2005DOUGLAS A. WOLF A decline has been found in the prevalence of disability among the older U.S. population during the 1980s and 1990s. One source of evidence for this decline is data from the National Long-Term Care Survey (NLTCS). This article investigates possible ambiguities in measuring disability using large-scale household surveys, illustrating the consequences of such problems with new analyses of NLTCS data. The reanalysis suggests a more gradual decline in disability than that found in prior research. The article also discusses three societal trends in areas other than health or functioning that might contribute to declines in disability levels: a reduced supply of informal care, changes in the technology of self-care, and changes in the definition and perception of both "ability" and "disability." [source] Dopamine-dependent motor learning: Insight into levodopa's long-duration responseANNALS OF NEUROLOGY, Issue 5 2010Jeff A. Beeler PhD Objective Dopamine (DA) is critical for motor performance, motor learning, and corticostriatal plasticity. The relationship between motor performance and learning, and the role of DA in the mediation of them, however, remain unclear. Methods To examine this question, we took advantage of PITx3-deficient mice (aphakia mice), in which DA in the dorsal striatum is reduced by 90%. PITx3-deficient mice do not display obvious motor deficits in their home cage, but are impaired in motor tasks that require new motor skills. We used the accelerating rotarod as a motor learning task. Results We show that the deficiency in motor skill learning in PITx3(,/,) is dramatic and can be rescued with levodopa treatment. In addition, cessation of levodopa treatment after acquisition of the motor skill does not result in an immediate drop in performance. Instead, there is a gradual decline of performance that lasts for a few days, which is not related to levodopa pharmacokinetics. We show that this gradual decline is dependent on the retesting experience. Interpretation This observation resembles the long-duration response to levodopa therapy in its slow buildup of improvement after the initiation of therapy and gradual degradation. We hypothesize that motor learning may play a significant, underappreciated role in the symptomatology of Parkinson disease as well as in the therapeutic effects of levodopa. We suggest that the important, yet enigmatic long-duration response to chronic levodopa treatment is a manifestation of rescued motor learning. ANN NEUROL 2010;67:639,647 [source] | ||||||||||||||||