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Biomedical subjects

R P Allen

Publications and source records attributed to R P Allen.

At least 19 recordsLinked to original sources
PubMed2004

Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a sensory-movement disorder affecting 5 to 10% of the population. Its etiology is unknown, but MRI analyses and immunohistochemical studies on autopsy tissue suggest the substantia nigra (SN) of patients with RLS has subnormal amounts of iron. METHODS: Neuromelanin cells from the SN of four RLS and four control brains were isolated by laser capture microdissection, and a profile of iron-management protein expression was obtained by immunoblot analysis. Binding assays for iron regulatory protein activity were performed on cell homogenates. RESULTS: Ferritin, divalent metal transporter 1, ferroportin, and transferrin receptor (TfR) were decreased in RLS neuromelanin cells compared with control. Transferrin was increased in RLS neuromelanin cells. This protein profile in RLS neuromelanin cells is consistent with iron deficiency with the exception that TfR expression was decreased rather than increased. The concentration and activity of the iron regulatory proteins (IRP1 and IRP2) were analyzed to determine whether there was a functional deficit in the post-transcriptional regulatory mechanism for TfR expression. Total IRP activity, IRP1 activity, and IRP1 protein levels were decreased in RLS, but total IRP2 protein levels were not decreased in RLS. CONCLUSION: Restless legs syndrome may result from a defect in iron regulatory protein 1 in neuromelanin cells that promotes destabilization of the transferrin receptor mRNA, leading to cellular iron deficiency.

Aged↗
PubMed2004

Validation of the Restless Legs Syndrome Quality of Life Instrument (RLS-QLI): findings of a consortium of national experts and the RLS Foundation.

UNLABELLED: This study was designed to assess the initial psychometric properties of a new disease-specific health-related quality of life (HRQL) measure, the Restless Legs Syndrome (RLS) Quality of Life Instrument (RLS-QLI). METHODS: Draft items were generated from a literature review, consultation with MD and PhD specialists in the fields of neurology and sleep medicine, and input from two patient focus groups. The initial item reduction was accomplished using a survey of 392 persons with self-reported RLS symptoms from the membership of the RLS Foundation. The final (independent) validation sample consisted of 574 of persons on the RLS Foundation's Interest Group List Serve who also reported having RLS. The mean age of participants was 54.5 (SD 12.3), with a sex ratio of 1M:2F, and the majority was on some form of medication for RLS (66%). RESULTS: Four factors were identified (Daily Function, Social Function, Sleep Quality, and Emotional Well-Being) consisting of 17 items that explained 73.3% of the total variance. Each scale had good internal consistency (Cronbach's alpha's between 0.85 and 0.91) and 2-week test retest stability (Pearson Correlations between 0.81 and 0.93). Convergent validity was demonstrated using related scales on the SF-36 (r = 0.47-0.60) and criterion-related validity was shown using the clinical IRLS Scale of Symptom Severity (r = -0.45 to -0.77). CONCLUSION: The RLS-QLI is a valid disease-specific HRQL instrument that will contribute to our understanding of how RLS impacts the lives of those affected with this CNS disorder.

Adult↗
PubMed2003

Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome.

OBJECTIVE: To assess neuropathology in individuals with restless legs syndrome (RLS). METHODS: A standard neuropathologic evaluation was performed on seven brains from individuals who had been diagnosed with RLS. The substantia nigra was examined in greater detail for iron staining and with immunohistochemistry for tyrosine hydroxylase and proteins involved in iron management. Five age-matched individuals with no neurologic history served as controls. RESULTS: There were no histopathologic abnormalities unique to the RLS brains. Tyrosine hydroxylase staining in the major dopaminergic regions appeared normal in the RLS brains. Iron staining and H-ferritin staining was markedly decreased in the RLS substantia nigra. Although H-ferritin was minimally detected in the RLS brain, L-ferritin staining was strong. However, the cells staining for L-ferritin in RLS brains were morphologically distinct from those in the control brains. Transferrin receptor staining on neuromelanin-containing cells was decreased in the RLS brains compared to normal, whereas transferrin staining in these cells was increased. CONCLUSIONS: RLS may not be rooted in pathologies associated with traditional neurodegenerative processes but may be a functional disorder resulting from impaired iron acquisition by the neuromelanin cells in RLS. The underlying mechanism may be a defect in regulation of the transferrin receptors.

Aged↗
PubMed2002

Increased CSF hypocretin-1 (orexin-A) in restless legs syndrome.

Hypocretin-1 levels were increased in evening CSF samples from subjects with restless legs syndrome, indicating altered hypocretin transmission in this sleep disorder. Increases in CSF hypocretin-1 levels were most striking in patients with early-onset restless legs syndrome.

Age of Onset↗
PubMed2002

Family history study of the restless legs syndrome.

BACKGROUND: Although there is a relatively high rate of occurrence of sporadic cases of restless legs syndrome (RLS), the systematic study of family history of RLS in populations of RLS patients has been very limited. The objective of the present study was to determine the risk of RLS for first- and second-degree relatives of a population of primary RLS patients not selected for the number of affected relatives in their families and to obtain an estimate of the degree of genetic involvement in RLS. METHODS: Consecutively consenting patients from two different sites who met the criteria for RLS completed a worksheet that asked them to indicate their current age, the date of their earliest RLS symptoms, and the names and RLS status of all of their first- and second-degree relatives. Controls with no clinical history of RLS also completed the worksheet. RESULTS: First- and second-degree relatives of patients with RLS had a significantly greater risk of RLS than the first- (P<0.001) and second-degree relatives (P<0.003) of controls. The risk of RLS was found to be greater for first-degree relatives of early-onset, rather than late-onset, RLS probands (P<0.001). CONCLUSIONS: This study provides a complete systematic examination of the risk of RLS among relatives of RLS probands and controls using the same assessment methodology. Although the results are consistent with a genetic etiology for RLS, they do not support the presence of one simple, Mendelian-inherited major gene in most RLS families.

Journal Article↗
PubMed2001

MRI measurement of brain iron in patients with restless legs syndrome.

Brain iron insufficiency in the restless legs syndrome (RLS) has been suggested by a prior CSF study. Using a special MRI measurement (R2'), the authors assessed regional brain iron concentrations in 10 subjects (five with RLS, five controls). R2' was significantly decreased in the substantia nigra, and somewhat less significantly in the putamen, both in proportion to RLS severity. The results show the potential utility of this MRI measurement, and also indicate that brain iron insufficiency may occur in patients with RLS in some brain regions.

Aged↗
PubMed2001

CSF dopamine, serotonin, and biopterin metabolites in patients with restless legs syndrome.

PURPOSE: To evaluate the role of CNS dopaminergic systems in Restless Legs Syndrome (RLS), homovanillic acid (HVA), tetrahydrobiopterin (BH4), and neopterin (NEOP), were assayed in CSF from RLS patients. The serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), was also measured. METHODS: CSF was taken from 16 RLS patients after 2 weeks off medication and from 14 control subjects. The CSF metabolites were determined using HPLC techniques. RESULTS: There was no significant difference in HVA or 5-HIAA, but NEOP and BH4 were higher in RLS patients. The RLS group was significantly older than the control group (64.2 +/- 9.2 years vs. 51.4 +/- 6.3 years; P < 0.001). A multiple regression analysis showed a strong correlation between age and 5-HIAA (r = 0.46, P = 0.04) and between age and NEOP (r = 0.61, P < 0.01). To eliminate the potential error created by the age difference between groups, an age-adjusted subgroup of RLS and control subjects were compared. There was still no difference found for HVA; however, 5-HIAA was now significantly lower (P < 0.01) in the RLS subgroup. Age-adjustment eliminated the differences previously found for NEOP, (P = 0.12), but BH4 continued to remain higher in the RLS group (P < 0.01). CONCLUSION: Differences in CSF HVA concentrations were not found. The changes in 5-HIAA and BH4 are of unclear clinical significance and require further assessment with appropriate age-matched controls.

Age Factors↗
PubMed2001

Restless legs syndrome: a review of clinical and pathophysiologic features.

Restless legs syndrome (RLS), although long ignored and still much underdiagnosed, disrupts the life and sleep considerably of those who have it. Recent clinical and basic research provides for better definition and pathophysiologic understanding of the disorder. The body of knowledge about this disorder has been expanding rapidly during the past decade and it has altered our concepts of this disorder. This review of RLS covers history, diagnosis, morbidity of sleep disturbance, relation to periodic limb movements in both sleep and waking, secondary causes, severity assessment methods, phenotypes for possible genetic patterns, epidemiology, pathophysiology, and medical treatment considerations. The emphasis on pathophysiology includes consideration of central nervous system localization, neurotransmitter and other systems involved, and the role of iron metabolism. Studies to date support the authors' recently advanced iron-dopamine model of RLS.

Anemia, Iron-Deficiency↗
PubMed2001

Investigation of preference for nightly triazolam versus placebo in moderate social alcohol drinkers.

This study was designed to examine whether the widely prescribed benzodiazepine hypnotic triazolam has reinforcing effects in moderate social alcohol drinkers, without histories of drug abuse or insomnia, in the context of its use as a hypnotic. Eleven healthy adult volunteers who met criteria for 'good sleepers' participated in a 60-session double-blind choice study which was conducted on an outpatient basis with participants sleeping at home. Twenty three-session sampling/choice tests were conducted sequentially to provide 20 evaluations of the reinforcing effects of 0.25 mg/70 kg triazolam versus placebo, ingested orally 30 min before bedtime. Each three-session test consisted of two sampling sessions, in which participants received exposure to each of the two drug conditions in different colored capsules, followed by one choice session, in which participants were asked to choose one of the two colour-coded capsules for self-administration. Four participants exhibited a significant choice of triazolam, three, a significant choice of placebo (i.e. triazolam avoidance), and four, a random (i.e. non-significant) choice between triazolam and placebo. The reasons provided by participants were consistent with their choices and with the expected effects of triazolam versus placebo. Analyses of post-sleep questionnaires indicated that triazolam did not produce a clinically meaningful improvement in sleep. The finding that triazolam functioned as a reinforcer in participants without insomnia suggests that triazolam has reinforcing effects in some individuals for which hypnotic treatment is not clinically indicated, and that health care professionals must continue to assess the risk/benefit ratio of benzodiazepine hypnotic prescription.

Adult↗
PubMed2000

Insight into the pathophysiology of restless legs syndrome.

Restless Legs Syndrome (RLS) is a disorder of sensation with a prevalence of around 2-5% of the population. Relevant to understanding the possible pathophysiological mechanism is the fact that RLS is extremely responsive to dopaminergic agents. A second issue is that iron deficiency states may precipitate RLS in as much as 25-30% of people with iron deficiency. Studies looking at basal ganglia dopaminergic function using PET and SPECT techniques have shown a decrease in binding potential for the dopamine receptor and transporter. Similar phenomena occurs in iron-deficient animals. Using MRI techniques and CSF analysis of iron-related protein, studies have suggested a reduction in brain iron concentration occurs in RLS patients. The relevance of CNS iron metabolism to the pathophysiology of RLS is discussed.

Animals↗
PubMed2000

Subclinical sensory neuropathy in late-onset restless legs syndrome.

OBJECTIVE: To determine the prevalence of different forms of peripheral neuropathy in patients with restless legs syndrome (RLS) and correlate the findings with other clinical characteristics. BACKGROUND: RLS is characterized by a desire to move the extremities, often associated with paresthesias or dysesthesias, motor restlessness, worsening of symptoms with rest with relief by activity, and worsening of symptoms in the evening or night. The association between RLS and peripheral neuropathy remains controversial. The observation that many patients with small-fiber neuropathy also complain of RLS prompted this prospective case series. METHODS: Twenty-two consecutive patients with RLS were evaluated for evidence of large-fiber neuropathy (LFN) and small sensory fiber loss (SSFL). RESULTS: In eight of the 22 (36%) patients, neuropathy was identified. Three patients had pure LFN; two had mixed LFN and SSFL; and three had isolated SSFL. The SSFL group had a later onset of RLS (p < 0.009), reported pain in their feet with RLS more frequently (p < 0.001), and tended to have no family history of RLS (p < 0.078). Patients with LFN did not have similar associations with age at onset, family history status, or presence of pain. CONCLUSION: The results suggest that two forms of RLS exist: one is triggered by painful dysesthesias associated with SSFL, has later onset, and no family history; and one without involvement of SSF, with an earlier onset age, positive family history for RLS, and no pain. The authors hypothesize that patients with the SSFL subtype of RLS will preferentially respond to neuropathic pain medications.

Adult↗
PubMed2000

Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome.

CSF and serum were obtained from 16 patients with idiopathic restless legs syndrome (RLS) and 8 age-matched healthy control subjects. Patients with RLS had lower CSF ferritin levels (1. 11 +/- 0.25 ng/mL versus 3.50 +/- 0.55 ng/mL; p = 0.0002) and higher CSF transferrin levels (26.4 +/- 5.1 mg/L versus 6.71 +/- 1.6 mg/L; p = 0.018) compared with control subjects. There was no difference in serum ferritin and transferrin levels between groups. The presence of reduced ferritin and elevated transferrin levels in CSF is indicative of low brain iron in patients with idiopathic RLS.

Adult↗
PubMed2000

Near infrared spectrophotometry for the diagnosis of vasculogenic erectile dysfunction.

A specialized near infrared spectrophotometry instrument for noninvasive, continuous monitoring of the hemodynamic events of erection in the human penis has been developed. Its potential application for the diagnostic evaluation of erectile dysfunction was investigated. Thirty-eight patients and 18 volunteer subjects underwent penile near infrared spectrophotometry using an optical sensor probe with wavelength selectivity for hemoglobin absorption spectra. Penile blood volume changes and their time courses were measured following intracavernous pharmacostimulation in patients and visual sexual stimulation in volunteers. Spectrophotometric results were compared with results obtained simultaneously using color duplex ultrasonography, strain gauge penile circumference monitoring, penile tonometry, and clinical assessments. Spectrophotometric recordings of penile erection showed measurable blood volume changes consistent with the hemodynamic events of this biological function. Blood volume per cent (BV%) increase correlated with clinical ratings of erection quality (P < 0.001), penile rigidity measurements (P < 0.005), and penile circumference increases (P < 0.0001), and it correlated with mean peak systolic velocity measurements when BV% increase was restricted to values less than 50% (P < 0.001). The time to reach half the maximum blood volume change (BV T1) correlated directly with the time to reach half the maximum penile circumference size increase (P < 0.001), whereas BV T4 correlated inversely with mean resistive index measurements only when BV T(1/2) was restricted to values greater than 120 s (P < 0.05). Spectrophotometric criteria consisting of BV % less than 35% and BV T(1/2) greater than 120 s affirmed the diagnosis of severe erectile impairment with a similar degree of accuracy as standard ultrasonographic criteria (P < 0.002). Penile near infrared spectrophotometry is a safe, inexpensive and simply used biomedical optics technique that provides quantitative measurements of the vascular physiology of penile erection and appears to offer clinical utility in the diagnosis of vasculogenic erectile dysfunction.

Adult↗
PubMed1999

Sleep, anxiety, and depression in abstinent and drinking alcoholics.

A group of alcoholic men were followed-up 8 years after discharge from hospital. The interview included items on sleep, anxiety, and depression. The sample was divided into abstinent and drinking subjects. Sleep data were factor analyzed. Only the Alcohol-Abstinence Sleep Factor significantly correlated with drinking status. The Alcohol-Abstinence Sleep Factor was also the primary correlate of anxiety and depression. Fewer abstinent subjects reported anxiety and depression. Sleep variables, anxiety, and depression are considered as possible markers of relapse in persons treated for alcoholism.

Adult↗
PubMed1998

Iron and the restless legs syndrome.

STUDY OBJECTIVES: Using blinded procedures, determine the relation between serum ferritin levels and severity of subjective and objective symptoms of the restless legs syndrome (RLS) for a representative patient sample covering the entire adult age range. DESIGN: All patient records from the past 4 years were retrospectively reviewed to obtain data from all cases with RLS. All patients were included who had ferritin levels obtained at about the same time as a polysomnogram (PSG), met diagnostic criteria for RLS, and were not on iron or medications that would reduce the RLS symptoms at the time of the PSG. SETTING: Sleep Disorders Center. PATIENTS: 27 (18 females, 9 males), aged 29-81 years. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Measurements included clinical ratings of RLS severity and PSG measures of sleep efficiency and periodic limb movements (PLMS) in sleep with and without arousal. Lower ferritin correlated significantly to greater RLS severity and decreased sleep efficiency. All but one patient with severe RLS had ferritin levels < or = 50 mcg/l. Patients with lower ferritin (< or = 50 mcg/l) also showed significantly more PLMS with arousal than did those with higher ferritin, but the PLMS/hour was not significantly related to ferritin. This last finding may be due to inclusion of two 'outliers' or because of severely disturbed sleep of the more severe RLS patients. CONCLUSIONS: These data are consistent with those from a prior unblinded study and suggest that RLS patients will have fewer symptoms if they have ferritin levels greater than 50 mcg/l.

Adult↗
PubMed1998

Randomized, double-blind, placebo-controlled trial of pergolide in restless legs syndrome.

OBJECTIVE: To assess the efficacy of pergolide in the treatment of restless legs syndrome (RLS). METHODS: A randomized, double-blind, parallel-treatment evaluation of pergolide versus placebo in patients with RLS was performed. Sixteen patients seen in the Sleep Disorders Center who met the clinical criteria for RLS were enrolled in the study. Treatment was either placebo (n=8) or pergolide (n=8), which was on a self-adjusted schedule that ranged from 0.05 to 0.65 mg/day. Outcome variables included the patient's rating of symptom improvement, duration of RLS symptoms throughout the day, and objective sleep assessments from an all-night polysomnogram (percent sleep efficiency and periodic leg movements). Baseline was assessed for 2 days before starting treatment. Dose adjustments were made over the first 14 days and were then held constant for 5 days, with repeat assessment for treatment effects on the last 2 days of treatment (days 17 and 18). RESULTS: As a group, pergolide recipients showed significant improvement clinically and statistically in all outcome measures when compared with baseline or with placebo treatment. On the other hand, placebo treatment led to no significant improvements in any outcome measures. CONCLUSIONS: Pergolide treatment significantly improved clinical symptoms and sleep efficiency, and reduced periodic limb movements of sleep in patients with RLS.

Adult↗