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Biomedical subjects

L Johnston

Publications and source records attributed to L Johnston.

At least 19 recordsLinked to original sources
PubMed2006

Contribution of reverse Na+-Ca2+ exchange to spontaneous activity in interstitial cells of Cajal in the rabbit urethra.

Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit regular Ca2+ oscillations that are associated with spontaneous transient inward currents (STICs) recorded under voltage clamp. Their frequency is known to be very sensitive to external Ca2+ concentration but the mechanism of this has yet to be elucidated. In the present study experiments were performed to assess the role of Na+-Ca2+ exchange (NCX) in this process. Membrane currents were recorded using the patch clamp technique and measurements of intracellular Ca2+ were made using fast confocal microscopy. When reverse mode NCX was enhanced by decreasing the external Na+ concentration [Na+]o from 130 to 13 mM, the frequency of global Ca2+ oscillations and STICs increased. Conversely, inhibition of reverse mode NCX by KB-R7943 and SEA0400 decreased the frequency of Ca2+ oscillations and STICs. Application of caffeine (10 mM) and noradrenaline (10 microM) induced transient Ca2+-activated chloride currents (I(ClCa)) at -60 mV due to release of Ca2+ from ryanodine- and inositol trisphosphate (IP3)-sensitive Ca2+ stores, respectively, but these responses were not blocked by KB-R7943 or SEA0400 suggesting that neither drug blocked Ca2+-activated chloride channels or Ca2+ release from stores. Intact strips of rabbit urethra smooth muscle develop spontaneous myogenic tone. This tone was relaxed by application of SEA0400 in a concentration-dependent fashion. Finally, single cell RT-PCR experiments revealed that isolated ICC from the rabbit urethra only express the type 3 isoform of the Na+-Ca2+ exchanger (NCX3). These results suggest that frequency of spontaneous activity in urethral ICC can be modulated by Ca2+ entry via reverse NCX.

Action Potentials↗
PubMed2006

Characterization of MspA, an immunogenic autotransporter protein that mediates adhesion to epithelial and endothelial cells in Neisseria meningitidis.

A novel putative autotransporter protein (NMB1998) was identified in the available genomic sequence of meningococcal strain MC58 (ET-5; ST-32). The mspA gene is absent from the genomic sequences of meningococcal strain Z2491 (ET-IV; ST-4) and the gonococcal strain FA1090. An orthologue is present in the meningococcal strain FAM18 (ET-37; ST-11), but the sequence contains a premature stop codon, suggesting that the protein may not be expressed in this strain. MspA is predicted to be a 157-kDa protein with low cysteine content, and it exhibits 36 and 33% identity to the meningococcal autotransporter proteins immunoglobulin A1 (IgA1) protease and App, respectively. Search of the Pfam database predicts the presence of IgA1 protease and autotransporter beta-barrel domains. MspA was cloned, and a recombinant protein of the expected size was expressed and after being affinity purified was used to raise rabbit polyclonal monospecific antiserum. Immunoblot studies showed that ca. 125- and 95-kDa fragments of MspA are secreted in meningococcal strain MC58, which are absent from the isogenic mutant. Secretion of MspA was shown to be modified in an AspA isogenic mutant. A strain survey showed that MspA is expressed by all ST-32 and ST-41/44 (lineage 3) strains, but none of the ST-8 (A4) strains examined. Sera from patients convalescing from meningococcal disease were shown to contain MspA-specific antibodies. In bactericidal assays, anti-MspA serum was shown to kill the homologous strain (MC58) and another ST-32 strain. Escherichia coli-expressing recombinant MspA was shown to adhere to both human bronchial epithelial cells and brain microvascular endothelial cells.

Animals↗
PubMed2005

Calcium oscillations in interstitial cells of the rabbit urethra.

Measurements were made (using fast confocal microscopy) of intracellular Ca2+ levels in fluo-4 loaded interstitial cells isolated from the rabbit urethra. These cells exhibited regular Ca2+ oscillations which were associated with spontaneous transient inward currents recorded under voltage clamp. Interference with D-myo-inositol 1,4,5-trisphosphate (IP3) induced Ca2+ release using 100 microm 2-aminoethoxydiphenyl borate, and the phospholipase C (PLC) inhibitors 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate and U73122 decreased the amplitude of spontaneous oscillations but did not abolish them. However, oscillations were abolished when ryanodine receptors were blocked with tetracaine or ryanodine. Oscillations ceased in the absence of external Ca2+, and frequency was directly proportional to the external Ca2+ concentration. Frequency of Ca2+ oscillation was reduced by SKF-96365, but not by nifedipine. Lanthanum and cadmium completely blocked oscillations. These results suggest that Ca2+ oscillations in isolated rabbit urethral interstitial cells are initiated by Ca2+ release from ryanodine-sensitive intracellular stores, that oscillation frequency is very sensitive to the external Ca2+ concentration and that conversion of the primary oscillation to a propagated Ca2+ wave depends upon IP3-induced Ca2+ release.

Anesthetics, Local↗
PubMed2005

Alternative, complementary, energy-based medicine for spinal cord injury.

This paper provides an overview on various alternative, complementary, or energy-based therapies that expand the healing spectrum of individuals with spinal cord injury (SCI). Not only do they have the capability to help a variety of secondary conditions, they have the ability in some people, for certain injuries, to restore function, sometimes dramatically. After providing an overall contextual rationale for the use of alternative medicine, this paper briefly summarizes various Eastern-medicine healing modalities, laser-based therapies, nutritional and homeopathic approaches, and pulsed electromagnetic therapies.

Clinical Trials as Topic↗
PubMed2005

Mirror movements in parkinsonism: evaluation of a new clinical sign.

BACKGROUND: Mirror movements (MM) are not widely appreciated in parkinsonism and no report has evaluated this clinical sign in detail. OBJECTIVES: To define the parkinsonian clinical features associated with MM in patients with early, asymmetric parkinsonism. METHODS: Twenty seven patients with early Parkinson's disease were evaluated using a standardised videotaping protocol. MM were scored from blinded video assessment using a clinical scale that rates the amplitude, distribution, and proportion of mirroring in the less affected limb. Parkinsonian features were combined into axial and lateralised scores using related items of the Unified Parkinson's Disease Rating Scale. RESULTS: MM were present in 24 of 27 patients. There was a significant linear correlation between the degree of asymmetry of motor deficits and MM on the less affected side. The effect of asymmetry was greater when the proportional rather than the absolute motor difference between sides was largest. Asymmetry in leg rigidity was the most important examination feature in the prediction of contralateral foot mirroring. CONCLUSIONS: MM are a clinical feature of the unaffected or less affected side in mild asymmetric parkinsonism. Their presence may be a useful clinical finding in early parkinsonism.

Adult↗
PubMed2005

A study of telephone screening and direct observation of surgical wound infections after discharge from hospital.

Post-discharge surveillance of surgical site infection is necessary if accurate rates of infection following surgery are to be available. We undertook a prospective study of 376 knee and hip replacements in 366 patients in order to estimate the rate of orthopaedic surgical site infection in the community. The inpatient infection was 3.1% and the post-discharge infection rate was 2.1%. We concluded that the use of telephone interviews of patients to identify the group at highest risk of having a surgical site infection (those who think they have an infection) with rapid follow-up by a professional trained to diagnose infection according to agreed criteria is an effective method of identifying infection after discharge from hospital.

Adult↗
PubMed2004

Habit retraining for the management of urinary incontinence in adults.

BACKGROUND: Habit retraining is toileting assistance given by a caregiver to adults with urinary incontinence. It involves the identification of an incontinent person's natural voiding pattern and the development of an individualised toileting schedule which pre-empts involuntary bladder emptying. OBJECTIVES: To assess the effects of habit retraining for the management of urinary incontinence in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised register (9 May 2002), MEDLINE (January 1966 to December 2002), EMBASE (January 1980 to Week 18 2002), CINAHL (January 1982 to February 2001), PsycINFO (January 1972 to current), Biological Abstracts (January 1980 to December 2000), Current Contents (January 1993 to December 2001) and the reference lists of relevant articles. We also contacted experts in the field, searched relevant websites and hand searched journals and conference proceedings. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing habit retraining delivered either alone or in conjunction with another intervention for urinary incontinence in adults. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were undertaken by at least two people working independently of each other. Any differences were resolved by discussion. The relative risks for dichotomous data were calculated with 95% confidence intervals. Where data were insufficient for a quantitative analysis, a narrative overview was undertaken. MAIN RESULTS: Three trials with a total of 337 participants met the inclusion criteria, describing habit retraining combined with other approaches compared with usual care. Participants were primarily care-dependent elderly women with concurrent cognitive and/or physical impairment, residing in either a residential aged-care facility or in their own home. Outcomes included incidence and/or severity of urinary incontinence, the prevalences of urinary tract infection, skin rash and skin breakdown, cost and caregiver preparedness, role strain and burden. Caregivers found it difficult to maintain voiding records and to implement the toileting program. A 61% compliance rate was reported in one trial. There were no statistically significant differences in the incidence and in the volume of incontinence between groups. Within group analyses did however show improvements on these measures. Reductions were also reported for the intervention group in one study for skin rash, skin breakdown and in caregivers' perceptions of their level of stress. Descriptive data on the intervention suggests that habit retraining is a labour-intense activity. Electronic loggers, used as an adjunct to caregiver-delivered wet/dry checks, were reported as providing more accurate data than that from caregiver conducted wet/dry checks. To date, no analysis of the time and resources associated with these comparisons is available. REVIEWERS' CONCLUSIONS: Data on habit retraining are few and of insufficient quality to provide a firm basis for practice.

Habits↗
PubMed2004

Timed voiding for the management of urinary incontinence in adults.

BACKGROUND: Timed voiding is a fixed time interval toileting assistance program that has been promoted for the management of people with urinary incontinence who cannot participate in independent toileting. For this reason, it is commonly assumed to represent current practice in residential aged care settings. OBJECTIVES: To assess the effects of timed voiding for the management of urinary incontinence in adults who cannot participate in independent toileting. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised register (9 May 2002), MEDLINE (January 1966 to December 2002), EMBASE (January 1980 to Week 18 2002), CINAHL (January 1982 to February 2001), PsycINFO (January 1972 to current), Biological Abstracts (January 1980 to December 2000), Current Contents (January 1993 to December 2001) and the reference lists of relevant articles. We also contacted experts in the field, searched relevant websites and handsearched journals and conference proceedings. SELECTION CRITERIA: We selected all randomised and quasi-randomised trials that addressed timed voiding in an adult population and that had an alteration in continence status as a primary outcome. We included those trials that had assessed timed voiding delivered either alone or in combination with another intervention and compared it with either usual care, or no timed voiding, or another intervention. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were undertaken by at least two people working independently of each other. Any differences were resolved by discussion until agreement was reached. The relative risk for dichotomous data were calculated with 95% confidence intervals. Where data were insufficient to support a quantitative analysis, a narrative overview was undertaken. MAIN RESULTS: Two trials with a total of 298 participants met the inclusion criteria. Both compared timed voiding plus additional intervention with usual care. In one of these timed voiding was combined with continence products, placement of a bedside commode for each participant, education to staff on transfer techniques, feedback and encouragement to staff, praise to participants for "successful responses" and administration of oxybutynin in small doses. The mean percentage who were incontinent when checked daily was 20% in the intervention group compared with 80% in the control group. No further between group analysis was possible from the data reported. The other trial combined timed voiding with a medical assessment and individualised medical management that was based on clinical data. Reduction in the number of participants with daytime and night-time incontinence was greater in the intervention group but this difference was statistically significant only for night-time wetting. There was no difference in the volume of urine lost as determined by pad weighing. The methodological quality of these trials was not high based on the quality appraisal criteria of the Cochrane Incontinence Group. In particular, there was a lack of clarity regarding levels of blinding. It was not possible to combine data from trials. In both trials, the fixed schedule of toileting was combined with other interventions. The extent to which the results reflect the contribution of timed voiding is unknown because the trials' design did not allow assessment of the effects of the fixed schedule of toileting separately from other components of the interventions. REVIEWER'S CONCLUSIONS: The data were too few and of insufficient quality to provide empirical support for or against the intervention of timed voiding.

Adult↗
PubMed2003

Hematopoietic cell transplantation from related and unrelated donors after minimal conditioning as a curative treatment modality for severe paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder caused by a somatic mutation of the X-linked phosphatidylinositol glycan class A gene. Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning is the only curative treatment; however, it is associated with high treatment-related mortality. Here, we report on allogeneic HCT for PNH after minimal conditioning. Seven adult patients with high-risk PNH underwent peripheral blood HCT from HLA-A-, -B-, -C-, -DRB1-, and -DQB1-matched related (n = 2) and unrelated (n = 5) donors. Conditioning included fludarabine 30 mg/m(2)/d on days -4 to -2 and 2 Gy of total body irradiation on day 0. After HCT, patients were given immunosuppressive therapy with oral cyclosporine starting on day -3 and mycophenolate mofetil starting on day 0. All 7 patients attained durable engraftment. After 28 days, a median of 77% (range, 53%-96%) T-cell donor chimerism was found in bone marrow and peripheral blood. T-cell chimerism increased to 91% (range, 76%-100%) on day +180 and to 100% in all surviving patients after 12 months. All 7 patients attained complete remissions of their disease. Four patients are alive 13 to 38 months after HCT. Three patients died of treatment-related mortality, 1 because of complications after acute pancreatitis and multiorgan failure, 1 because of infection related to chronic graft-versus-host disease (GVHD), and 1 because of bleeding after liver biopsy for late subacute/chronic GVHD. Allogeneic HCT from related and unrelated donors after minimal conditioning is a new and potentially curative option for patients with advanced PNH.

Adolescent↗
PubMed2003

Starch fermentation by faecal bacteria of infants, toddlers and adults: importance for energy salvage.

OBJECTIVE: Little is known of the degree to which the colon salvages energy through starch fermentation in young children. Using a simulated colonic environment, we aimed to account for the fate of fermented raw and cooked starch in two groups of young children and in adults. DESIGN: A slurry was prepared from faecal samples from six infants (7-10 months), six toddlers (16-21 months) and seven adults (24-56 y). Each slurry was anaerobically incubated with raw or cooked maize starch in MacCartney bottles in a shaking water bath. Parallel incubations were stopped at 4 and 24 h. The headspace gas volume was analysed for CO(2) and methane. The culture supernatant was analysed for short-chain fatty acids (SCFA), lactate and residual starch. RESULTS: Different patterns of fermentation were seen at 4 and 24 h. For raw starch, the production of SCFA decreased with subject age at 4 h but not at 24 h. With both substrates at 4 h, toddler stools produced significantly more CO(2) than infants or adults, but there were no statistical differences at 24 h. Methane was detected in three adults only. Lactate was detected mainly at 4 h in children. CONCLUSIONS: The results suggest that fermentation, particularly of raw starch, is a more rapid process in young children than in adults. A highly efficient energy salvage process may occur in the colon of young children.

Adult↗
PubMed2003

Oral sucrose for procedural pain in sick hospitalized infants: a randomized-controlled trial.

OBJECTIVE: To determine the efficacy of 25% oral sucrose in the reduction of pain during a heel lance procedure in sick hospitalized infants. METHODOLOGY: In a blinded randomized- controlled trial, hospitalized infants were given either 1 mL 25% sucrose or 1 mL water 2 min prior to a heel lance procedure. Pain assessment comprised a four-point facial expression score, incidence and duration of crying, heart rate and oxygen saturation changes. RESULTS: A total of 128 infants were included. Facial scores immediately upon heel lance, and at 1 and 2 min in the recovery period were reduced in the treatment (sucrose) group compared to the placebo (water) group (P < 0.05). At other observation points, the differences in facial scores between the two groups of infants did not reach statistical significance. Neither incidence nor duration of crying whilst the blood collection was in progress was significantly reduced by sucrose. In the 3-min recovery period following completion of the blood collection, incidence and duration of crying were significantly less in the treatment group of infants (P < 0.05). Physiological responses of heart rate and oxygen saturation were not attenuated by sucrose at any time point during or following the blood collection. CONCLUSION: Oral sucrose was effective in reducing behavioural responses to pain upon heel lance and in the period following completion of a heel lance procedure in this group of sick hospitalized infants. This simple strategy can be promoted in institutions caring for sick babies, as a method of reducing behavioural responses to procedural pain.

Administration, Oral↗
PubMed2003

Modelling the influence of irrigation abstractions on Scotland's water resources.

Legislation to control abstraction of water in Scotland is limited and for purposes such as irrigation there are no restrictions in place over most of the country. This situation is set to change with implementation of the European Water Framework Directive. As a first step towards the development of appropriate policy for irrigation control there is a need to assess the current scale of irrigation practices in Scotland. This paper presents a modelling approach that has been used to quantify spatially the volume of water abstractions across the country for irrigation of potato crops under typical climatic conditions. A water balance model was developed to calculate soil moisture deficits and identify the potential need for irrigation. The results were then combined with spatial data on potato cropping and integrated to the sub-catchment scale to identify the river systems most at risk from over-abstraction. The results highlight that the areas that have greatest need for irrigation of potatoes are all concentrated in the central east-coast area of Scotland. The difference between irrigation demand in wet and dry years is very significant, although spatial patterns of the distribution are similar.

Agriculture↗
PubMed2001

Imagery rehearsal therapy for chronic nightmares in sexual assault survivors with posttraumatic stress disorder: a randomized controlled trial.

CONTEXT: Chronic nightmares occur frequently in patients with posttraumatic stress disorder (PTSD) but are not usually a primary target of treatment. OBJECTIVE: To determine if treating chronic nightmares with imagery rehearsal therapy (IRT) reduces the frequency of disturbing dreams, improves sleep quality, and decreases PTSD symptom severity. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted from 1995 to 1999 among 168 women in New Mexico; 95% had moderate-to-severe PTSD, 97% had experienced rape or other sexual assault, 77% reported life-threatening sexual assault, and 58% reported repeated exposure to sexual abuse in childhood or adolescence. INTERVENTION: Participants were randomized to receive treatment (n = 88) or to the wait-list control group (n = 80). The treatment group received IRT in 3 sessions; controls received no additional intervention, but continued any ongoing treatment. MAIN OUTCOME MEASURES: Scores on the Nightmare Frequency Questionnaire (NFQ), Pittsburgh Sleep Quality Index (PSQI), PTSD Symptom Scale (PSS), and Clinician-Administered PTSD Scale (CAPS) at 3- and 6-month follow-up. RESULTS: A total of 114 participants completed follow-up at 3 and/or 6 months. Comparing baseline to follow-up (n = 97-114), treatment significantly reduced nights per week with nightmares (Cohen d = 1.24; P<.001) and number of nightmares per week (Cohen d = 0.85; P<.001) on the NFQ and improved sleep (on the PSQI, Cohen d = 0.67; P<.001) and PTSD symptoms (on the PSS, Cohen d = 1.00; P<.001 and on the CAPS, Cohen d = 1.53; P<.001). Control participants showed small, nonsignificant improvements for the same measures (mean Cohen d = 0.21). In a 3-point analysis (n = 66-77), improvements occurred in the treatment group at 3-month follow-up (treatment vs control group, Cohen d = 1.15 vs 0.07 for nights per week with nightmares; 0.95 vs -0.06 for nightmares per week; 0.77 vs 0.31 on the PSQI, and 1.06 vs 0.31 on the PSS) and were sustained without further intervention or contact between 3 and 6 months. An intent-to-treat analysis (n = 168) confirmed significant differences between treatment and control groups for nightmares, sleep, and PTSD (all P<.02) with moderate effect sizes for treatment (mean Cohen d = 0.60) and small effect sizes for controls (mean Cohen d = 0.14). Posttraumatic stress symptoms decreased by at least 1 level of clinical severity in 65% of the treatment group compared with symptoms worsening or not changing in 69% of controls (chi(2)(1) = 12.80; P<.001). CONCLUSIONS: Imagery rehearsal therapy is a brief, well-tolerated treatment that appears to decrease chronic nightmares, improve sleep quality, and decrease PTSD symptom severity.

Adult↗
PubMed2001

Rapid engraftment after allogeneic transplantation of density-enriched peripheral blood CD34+ cells in patients with advanced hematologic malignancies.

BACKGROUND: Acute graft versus host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Preclinical studies have suggested that a T-cell subset with a CD4-/CD8- double-negative (DN) T-cell phenotype is capable of suppressing GVHD. Double-negative T cells can be mobilized into the peripheral blood with granulocyte colony-stimulating factor (G-CSF) and enriched by density centrifugation. The current study was performed to study the feasibility and safety of applying a density gradient separation technique for enrichment of CD34+ and DN T cells, while depleting CD4+ and CD8+ single-positive (SP) T cells from peripheral blood progenitor cells (PBPCs) for the purpose of allogeneic transplantation. METHODS: Twenty-five patients with advanced hematologic malignancies were treated with a myeloablative preparative regimen consisting of fractionated total body irradiation, etoposide, and cyclophosphamide. Human leukocyte antigen identical donors were mobilized with G-CSF PBPC collected by apheresis. The apheresis product was applied to a single-step density gradient, and the low-density cell population was collected. The low-density cell population was infused as the sole source of allogeneic cells after myeloablative therapy. Graft versus host disease prophylaxis consisted of cyclosporine with or without prednisone. RESULTS: CD34 cell recovery was efficient with a median 72% yield, providing for a median CD34+ cell dose of 6.5 x 10(6)/kg (range,1.0- 13.9 x 10(6)/kg). CD3+CD4+ or CD3+CD8+ SP T cells were depleted by a median of 94.4% (range, 58.8- 99.2%), and the ratio of CD34+:SP T cells increased 10-fold. Double-negative T cells were depleted by 92% (range, 18.8- 99.4%), thus the ratio of DN:SP T cells increased less than 2-fold in 71% of apheresis samples tested. Hematopoietic engraftment was rapid, and there was no occurrence of graft failure in examinable patients. Median time to absolute neutrophil count greater than 0.5 x 10(9)/L and platelet count greater than 20 x 10(9)/L was 10.5 and 12 days, respectively. The incidence of Grade 2-4 acute GVHD was 26% (95% confidence interval [CI], 6-45%), although not all patients were examinable due to an unexpectedly high nonrecurrence mortality that at Day 180 was 62% (95% CI, 40-83%). CONCLUSIONS: These data suggest that T-cell subset manipulation via density gradient separation is a safe procedure and allowed rapid hematopoietic recovery. Selective enrichment of a donor DN T-cell subset was observed in only a few and was not associated with a reduced incidence of GVHD. However, the low-density selected cells still resulted in GVHD, and there was a high treatment-related mortality.

Adult↗
PubMed2001

Complex insomnia: insomnia and sleep-disordered breathing in a consecutive series of crime victims with nightmares and PTSD.

BACKGROUND: Sleep disturbance in posttraumatic stress disorder is very common. However, no previous posttraumatic stress disorder studies systematically examined sleep breathing disturbances, which might influence nightmares, insomnia, and posttraumatic stress disorder symptoms. METHODS: Forty-four consecutive crime victims with nightmares and insomnia underwent standard polysomnography coupled with a nasal pressure transducer to measure airflow limitation diagnostic of obstructive sleep apnea and upper airway resistance syndrome. RESULTS: Forty of 44 participants tested positive on objective sleep studies based on conservative respiratory disturbance indices of more than 15 events per hour; 22 patients suffered from obstructive sleep apnea and 18 suffered from upper airway resistance syndrome. CONCLUSIONS: In an uncontrolled study, insomnia and sleep-disordered breathing were extremely prevalent in this small and select sample of crime victims. Research is needed to study 1) prevalence of sleep-disordered breathing in other posttraumatic stress disorder populations using appropriate controls and nasal pressure transducers and 2) effects of sleep treatment on posttraumatic stress symptoms in trauma survivors with comorbid obstructive sleep apnea or upper airway resistance syndrome. In the interim, some posttraumatic stress disorder patients may benefit from sleep medicine evaluations.

Adult↗
PubMed2001

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗