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Biomedical subjects

R Lane

Publications and source records attributed to R Lane.

At least 19 recordsLinked to original sources
PubMed2006

Cardiac safety of rivastigmine in Lewy body and Parkinson's disease dementias.

Cholinesterase inhibition in patients with Alzheimer's disease (AD) may affect heart rate, sometimes inducing bradycardia. Additional cardiac safety considerations apply in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PDD), in whom cardiovascular autonomic nervous system dysfunction is common. We conducted a review of the safety data available for rivastigmine in these two conditions. A modest reduction in the mean heart rate of 1.5-2 bpm was seen. No clinically meaningful treatment differences in bradycardia or ECG abnormalities were apparent. Compared with placebo, rivastigmine appeared to be associated with fewer vascular disorder adverse events (AEs) (p = 0.002) and fewer AEs of syncope (p = 0.018) in PDD patients (n = 541). A smaller randomised, placebo-controlled study of rivastigmine in DLB (n = 120) showed similar findings. Rivastigmine appears to have a favourable cardiac safety profile in PDD and DLB patients.

Aged↗
PubMed2005

Benefits of rivastigmine on attention in dementia associated with Parkinson disease.

In a 24-week, randomized, double-blind, placebo-controlled, multicenter study of rivastigmine, 487 patients with dementia associated with Parkinson disease underwent assessment of attention on the Cognitive Drug Research computerized cognitive assessment system before dosing and 16 and 24 weeks later. Significant benefits of rivastigmine over placebo were seen on all aspects of attention assessed: sustained attention, focused attention, consistence of responding, and central processing speed.

Aged↗
PubMed2004

Impact of APOE in mild cognitive impairment.

OBJECTIVE: The authors aimed to use baseline data of an ongoing large, prospective study in subjects with mild cognitive impairment (MCI) to investigate the impact of APOE genotype on the symptom profile of the condition. METHODS: Cognitive assessments included the AD Assessment Scale cognitive subscale (ADAS-cog), the Mini-Mental State Examination (MMSE), and a cognitive battery for assessment of memory, attention, and executive function. Behavioral assessments included the Neuropsychiatric Inventory and Beck Depression Inventory. Activities of daily living were assessed by the AD Cooperative Study Activities of Daily Living (ADCS-ADL) scale. Hippocampal volumes were measured with MRI. RESULTS: A total of 494 of 1,018 study subjects provided APOE data. Approximately 40% of the subjects were APOE epsilon4 carriers. APOE epsilon4 carriers had lower MMSE (p = 0.01) and higher ADAS-cog (p < 0.0001) scores than noncarriers, indicating worse cognitive impairment. APOE epsilon4 carriers also had greater deficits on New York University delayed paragraph recall and Buschke free and cued selective reminding tests, and on the ADCS-ADL scale (p < 0.001). They also had smaller hippocampal volumes (p = 0.002). Behavioral scores were similar across the subgroups. CONCLUSION: MCI subjects carrying the APOE epsilon4 allele showed distinct cognitive and imaging profiles, which appeared to resemble those of early Alzheimer patients. APOE epsilon4 genotype was associated with greater impairments in memory and functional activities as well as hippocampal atrophy.

Activities of Daily Living↗
PubMed2004

Behavioral symptoms in mild cognitive impairment.

The authors investigated neuropsychiatric symptoms in mild cognitive impairment (MCI) from baseline data of the Investigation in the Delay to Diagnosis of AD with Exelon (InDDEx) study (n = 1,010). Neuropsychiatric symptoms were reported in 59% of subjects (Neuropsychiatric Inventory [NPI]). NPI+ subjects had significantly greater impairment on global, cognitive, and functional scores than NPI- subjects. The presence of neuropsychiatric symptoms appears to be a marker of MCI severity.

Aged↗
PubMed2004

Differential qualitative responses to rivastigmine in APOE epsilon 4 carriers and noncarriers.

This retrospective analysis of two double-blind, placebo-controlled studies in patients with mild to moderately severe AD investigated the efficacy of rivastigmine 6-12 mg/day on cognitive outcomes in patients with or without the apolipoprotein (APOE) epsilon4 allele. APOE data were collected from patients who consented to pharmacogenetic testing. Treatment differences within each subgroup were compared, using the Observed Case (OC) population. The APOE epsilon4 and non-APOE epsilon4 subgroups comprised 246 and 121 patients, respectively. Overall, APOE epsilon4 noncarriers showed greater decline than carriers (P<0.05). However, at 26 weeks, placebo-treated APOE epsilon4 patients declined 3.04 points below baseline on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), and rivastigmine-treated patients improved by 1.67 points. Non-APOE epsilon4 placebo-treated patients declined by 4.59 points and rivastigmine-treated patients declined by 0.48 points. Thus, non-APOE epsilon4 carriers showed a less favorable course under either placebo or rivastigmine, but both genotype-defined subgroups showed quantitatively similar responses to therapy (both P<0.05 vs placebo).

Aged↗
PubMed2003

Potential long-term effects of rivastigmine on disease progression may be linked to drug effects on vascular changes in Alzheimer brains.

Alzheimer's disease patients with hypertension or other vascular risk factors have been shown to receive greater symptomatic benefits than patients with strictly Alzheimer's disease following short-term treatment with rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase. We evaluated the long-term efficacy of rivastigmine in Alzheimer's disease patients with or without hypertension. Subjects in a 26-week placebo-controlled trial of rivastigmine entered an open-label extension study for 104 weeks. Efficacy measures included the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Progressive Deterioration Scale (PDS) and Global Deterioration Scale (GDS). Subjects were stratified by the presence or absence of hypertension at baseline. At 104 weeks, there was a trend for hypertensive patients from the original rivastigmine 6-12 mg/day group (early starters), who received rivastigmine for the full 104 weeks) to have better ADAS-cog scores than the original placebo group (late starters), who received open-label rivastigmine for the last 78 weeks only). Significant treatment differences were observed in the hypertensive subgroup on the PDS and GDS. In non-hypertensive patients, changes from baseline at week 104 were similar in 'early' and 'late' starters of rivastigmine treatment. The additional apparent benefits on disease progression detected in patients with hypertension and Alzheimer's disease may be linked to drug effects on cerebrovascular factors. These findings may have an important influence on the way cholinesterase inhibitors are prescribed.

Aged↗
PubMed2002

The use of nasal continuous positive airway pressure to treat obstructive sleep apnoea.

AIM: To review 66 children with obstructive sleep apnoea (OSA) for whom a trial of nasal continuous positive airway pressure (nCPAP) was proposed. METHODS: Baseline sleep studies were performed to assess OSA severity; a trial of nCPAP was performed where moderate to severe OSA, not relieved by adenotonsillectomy, was found. The nCPAP trial was considered either technically successful (ST), if the child accepted the mask for sufficient time to determine nCPAP efficacy, or a technical failure (FT) if otherwise. Patients with an initial FT were offered a period of home acclimatisation to familiarise them with wearing the mask during sleep. ST patients in whom nCPAP was effective were established on long term therapy. RESULTS: Nasal CPAP trials were successful (ST) in 49/66 (74%) patients. Nasal CPAP efficacy could not be determined in the remaining 17 FT patients (26%), generally because of their poor nCPAP tolerance. These patients were subsequently considered for other treatment. A total of 42/49 (86%) ST patients were established on long term nCPAP therapy, 2/49 (4%) derived no benefit from nCPAP, while 5/49 (10%) refused long term nCPAP therapy. Of patients on long term nCPAP, the most frequently reported side effects were skin irritation and nasal dryness; however, these were not serious enough to require any patients to discontinue therapy. A period of home acclimatisation was found to be effective in increasing nCPAP acceptance, with 26% of FT children being subsequently successfully reassessed for nCPAP. CONCLUSION: The use of nCPAP was feasible in a significant proportion of a paediatric OSA population. Failure was usually because of the child's intolerance of the nCPAP equipment. Nasal CPAP was an effective treatment in the majority of patients where it could be assessed, and was adopted as a long term therapy in most cases. We have successfully used nCPAP to treat OSA across a wide range of ages. Motivated parents and skilled support staff have proved essential for the success of nCPAP in a paediatric setting.

Adolescent↗
PubMed2002

Rivastigmine in patients with Alzheimer's disease and concurrent hypertension.

Rivastigmine has demonstrated significant benefits in patients with mild to moderate Alzheimer's disease (AD). We aimed to confirm whether rivastigmine was effective in patients with or without concurrent vascular risk factors (VRF), as previously suggested. We chose to stratify the 725 patients involved in an international dose-ranging study according to the presence of arterial hypertension (a marker of VRF) at baseline. Efficacy in each subgroup was assessed using the ADAS-cog, a measure of cognitive performance, the Progressive Deterioration Scale (PDS) and the Clinician's Interview-Based Impression of Change (CIBIC) with caregiver input. Patients receiving rivastigmine 6-12 mg/day showed better outcomes on the ADAS-cog than those receiving placebo, in both the hypertensive and non-hypertensive subgroups. Hypertensive patients receiving rivastigmine 6-12 mg/day also showed improvement over those receiving 1-4 mg/day (p = 0.023). Rivastigmine 6-12 mg/day also provided better outcomes than placebo on the PDS in the hypertensive (p = 0.031) and non-hypertensive (p = 0.035) subgroups. All patients receiving rivastigmine 6-12 mg/day had superior CIBIC-plus scores than those receiving placebo. There was a trend for lower incidences of nausea and vomiting in rivastigmine-treated patients with hypertension than in those without hypertension. No cardiac adverse events or drug-drug interactions were reported. Our data support the hypothesis that rivastigmine provides benefits to patients with or without hypertension, and contribute to the evidence that particular benefits may be observed in those with vascular risk factors.

Aged↗
PubMed2001

Nocturnal hypoxaemia and central-nervous-system events in sickle-cell disease.

BACKGROUND: Central-nervous-system (CNS) events, including strokes, transient ischaemic attacks, and seizures are common in sickle-cell disease. Stroke can be predicted by high velocities in the internal-carotid or middle-cerebral arteries on transcranial doppler ultrasonography. We tested the hypothesis that nocturnal hypoxaemia can predict CNS events better than clinical or haematological features, or transcranial doppler sonography. METHODS: We screened 95 hospital-based patients with sickle-cell disease (median age 7.7 years [range 1.0-23.1]), but without previous stroke, with transcranial doppler and overnight pulse oximetry. Follow-up continued for a median of 6.01 (0.11-8.54) years. FINDINGS: 19 patients had CNS events (six ischaemic and one haemorrhagic stroke, eight transient ischaemic attacks, and four seizures). Mean overnight oxygen saturation ([SaO(2)] hazard ratio 0.82 per 1% increase [95% CI 0.71-0.93]; p=0.003) and higher internal-carotid or middle-cerebral artery velocity (1.02 for every increase of 1 cm/s [1.004-1.03]; p=0.009) were independently associated with time to CNS event. After accounting for mean SaO(2), artery velocity, and haemoglobinopathy, high haemoglobin concentration was also associated with an increased risk of CNS event (1.7 per g/dL, [1.18-2.43]; p=0.004). Dips suggestive of obstructive sleep apnoea did not predict CNS events, and adenotonsillectomy seemed to have no effect, although the CI were wide and clinically important effects cannot be excluded. INTERPRETATION: Screening for, and appropriate management of, nocturnal hypoxaemia might be a safe and effective alternative to prophylactic blood transfusion for primary prevention of CNS events in sickle-cell disease.

Adolescent↗
PubMed2001

Disordered breathing during sleep in patients with mucopolysaccharidoses.

OBJECTIVE: Obstructive sleep apnoea (OSA) has been reported as a feature of children with mucopolysaccharidoses (MPS). However, the incidence and severity of OSA with respect to disease type is poorly defined. The aim of the present study was to measure objectively the degree of OSA in a group of children with a range of MPS syndromes. METHODS: In a cross-sectional study, cardiopulmonary sleep studies were performed during unsedated sleep in 26 children with MPS over a period of 2 years. Scores of OSA severity based upon clinical history and upon objective sleep study data were made in each case and compared. RESULTS: OSA was present in 24/26 patients, and ranged in severity from mild to severe. OSA was most marked in MPS type IH (Hurler syndrome) followed by types IHS (Hurler--Scheie syndrome) and II (Hunter syndrome). Frequent arousals and poor sleep quality, not suspected clinically, were noted in several patients. There was agreement between the clinical and objective scoring systems in only 17/26 patients (65%) with clinical history scores tending to underestimate the most severe cases (5/26 cases) and overestimate the severity in the mild cases (4/26 cases). CONCLUSIONS: Obstructive respiratory problems are frequent in MPS patients and there are differences in severity of OSA between the different MPS types. Assessments of the severity of OSA based upon clinical history alone are inadequate. Our results suggest that objective sleep studies are necessary to evaluate these cases, to monitor clinical outcome and to assess the effects of therapeutic intervention. Prospective studies in larger numbers of patients are needed to validate these observations.

Adolescent↗
PubMed2000

Immune reactivity to glutamic acid decarboxylase 65 in stiffman syndrome and type 1 diabetes mellitus.

BACKGROUND: The immune response to an isoform of glutamic acid decarboxylase (GAD), GAD65, is associated with two clinically distinct diseases, stiff-man syndrome (SMS) and type 1 (insulin-dependent) diabetes mellitus. We sought to identify differences in the cellular and humoral immune responses to GAD in these two diseases. METHODS: We compared T-cell responses in 14 SMS patients with axial disease and 17 patients with type 1 diabetes. FINDINGS: Peripheral blood T cells of eight SMS patients recognised different immunodominant epitopes of GAD65 compared with T cells from 17 patients with type 1 diabetes. GAD regions 81-171 and 313-403 induced a dominant T-cell response in six of eight patients with SMS but in only one of 17 patients with type 1 diabetes (p=0.001). No SMS patients responded dominantly to GAD fragments 161-243 and 473-555 compared with ten patients with type 1 diabetes (p=0.008). GAD antibodies were detected in 11 of 14 SMS patients (seven with diabetes) and 11 of 17 patients with type 1 diabetes; IgG1 was dominant in both groups. SMS patients, however, were more likely than patients with diabetes to have isotypes other than IgG1 (p=0.03), in particular, IgG4 or IgE isotypes, which were not detected in patients with type 1 diabetes (p=0.012). INTERPRETATION: Our findings indicate differences between patients with SMS and type 1 diabetes in cellular (epitope recognition) and humoral (isotype pattern) responses to GAD65. Thus the same autoantigen can elicit distinct immune responses in patients with SMS, even when associated with diabetes, compared with patients with type 1 diabetes.

Adolescent↗
PubMed2000

Dissociable temporal lobe activations during emotional episodic memory retrieval.

The richness of human recollective experience is, in part, related to evocation of previously experienced emotions. An extensive functional neuroimaging literature has provided a description of brain regions involved in retrieving emotionally neutral episodic memories. Whether similar or distinct systems are involved in retrieving emotional memories is unresolved. This question motivated the present functional neuroimaging study, using 0-15 positron emission tomography (PET), where we compared patterns of brain activation associated with retrieving previously studied emotional and neutral pictorial material. By varying task requirements and item density we characterized two distinct neural response patterns during emotional memory retrieval. First, we identified an anterior temporal pole activation that reflected the psychological set associated with emotional memory retrieval. Second, we identified a left amygdala response sensitive to actual retrieval of emotional items. These data suggest distinct functional roles for temporal lobe regions during emotional memory retrieval involving context-related tonic anterior temporal pole activation and a phasic item-related amygdala response. We conclude that brain regions involved in episodic memory retrieval reflect not only physical attributes of stimulus material, for example, their verbal or visual qualities, but also their affective significance.

Amygdala↗
PubMed2000

A novel intermittent regimen of norgestimate to preserve the beneficial effects of 17beta-estradiol on lipid and lipoprotein profiles.

OBJECTIVE: This study was undertaken to evaluate the effects of 3 dosage levels of intermittent norgestimate plus a constant dose of 17beta-estradiol on blood lipid and lipoprotein concentrations in 236 postmenopausal women. STUDY DESIGN: In this multicenter, double-blind, parallel-group trial the subjects were randomly assigned to receive 1 mg estradiol daily or 1 mg estradiol daily plus intermittent (3 days off and 3 days on) doses of 30 microg, 90 microg, or 180 microg norgestimate for 360 days. RESULTS: The regimens of 1 mg estradiol plus 30 microg norgestimate and 1 mg estradiol plus 90 microg norgestimate increased concentrations of high-density lipoprotein cholesterol, HDL(2) high-density lipoprotein cholesterol, HDL(3) high-density lipoprotein cholesterol (except the regimen of 1 mg estradiol plus 30 microg norgestimate at 7 months), and apolipoprotein apo A-I. They decreased total cholesterol concentration, low-density lipoprotein cholesterol concentration, low-density lipoprotein/high-density lipoprotein ratio, apolipoprotein apo B concentration, and Lp(a) lipoprotein concentration, and they attenuated estradiol-induced increases in triglyceride concentrations. In contrast, the regimen of 1 mg estradiol plus 180 microg norgestimate reduced concentrations of high-density lipoprotein cholesterol, high-density lipoprotein HDL(3) cholesterol, and apolipoprotein apo A-I at 7 months and increased the low-density lipoprotein/high-density lipoprotein ratio at 7 months. CONCLUSIONS: An intermittent regimen of norgestimate at 30 or 90 microg daily administered for 3 days off followed by 3 days on preserved the beneficial lipid and lipoprotein changes induced by continuous therapy with 1 mg 17beta-estradiol daily; however, 180 microg norgestimate did not do so.

Adult↗
PubMed2000

Platelet and leucocyte activation in childhood sickle cell disease: association with nocturnal hypoxaemia.

We hypothesized that vaso-occlusive events in childhood sickle cell disease (SCD) may relate to inflammatory cell activation as well as interactions between sickle erythrocytes and vascular endothelium. Peripheral blood was examined from 24 children with SCD, of whom 12 had neurological sequelae and seven had frequent painful crises, and 10 control subjects. Platelet (CD62P and CD40L expression) and granulocyte (CD11b expression) activation and levels of platelet-erythrocyte and platelet-granulocyte complexes were determined by flow cytometry. Platelets (P = 0.019), neutrophils (P = 0.02) and monocytes (P = 0.001) were more activated and there were increased platelet-erythrocyte complexes (P = 0.026) in SCD patients compared with controls. Platelet-granulocyte complexes were not raised. There were no differences between the different groups of SCD. As hypoxia activates monocytes, platelets and endothelial cells and causes sickling of SCD erythrocytes, we also investigated 20 SCD patients with overnight pulse oximetry. Minimum overnight saturation correlated with the level of platelet-erythrocyte complexes (Spearman's rho -0.668, P < 0.02), neutrophil CD11b (Spearman's rho -0.466, P = 0.038) and monocyte CD11b (Spearman's rho -0.652, P = 0. 002). These findings provide important clues about the mechanism by which SCD patients may become predisposed to vaso-occlusive events.

Adolescent↗
PubMed2000

An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue.

OBJECTIVES: This study was designed to evaluate the efficacy and safety of the oxytocin receptor antagonist atosiban in the treatment of preterm labor. STUDY DESIGN: A multicenter, double-blind, placebo-controlled trial with tocolytic rescue was designed. Five hundred thirty-one patients were randomized to receive, and 501 received, either intravenous atosiban (n = 246) or placebo (n = 255), followed by subcutaneous maintenance with the assigned agent. Standard tocolytics as rescue tocolysis were permitted after 1 hour of either placebo or atosiban if preterm labor continued. The primary end point was the time from the start of study drug to delivery or therapeutic failure. Secondary end points were the proportion of patients who remained undelivered and did not receive an alternate tocolytic at 24 hours, 48 hours, and 7 days. RESULTS: No significant difference was found in the time from start of treatment to delivery or therapeutic failure between atosiban and placebo (median, 25.6 days vs 21.0 days, respectively; P =.6). The percentages of patients remaining undelivered and not requiring an alternate tocolytic at 24 hours, 48 hours, and 7 days were significantly higher in the atosiban group than in the control group (all P < or =.008). A significant treatment-by-gestational age interaction existed for the 48-hour and 7-day end points. Atosiban was consistently superior to placebo at a gestational age of > or =28 weeks. Fourteen atosiban-treated patients and 5 placebo-treated patients were randomized at <24 weeks; the incidence of fetal-infant deaths was higher for the atosiban group at <24 weeks. Maternal-fetal adverse events were similar except for injection-site reactions, which occurred more often with atosiban. CONCLUSIONS: In this trial the treatment of patients in preterm labor with atosiban resulted in prolongation of pregnancy for up to 7 days for those at a gestational age > or =28 weeks, and this occurred with a low rate of maternal-fetal adverse effects. In addition, at a gestational age > or =28 weeks, the infant morbidity and mortality of atosiban-initiated standard care were similar to those with placebo-initiated standard care. Given that all patients in this study were eligible for tocolysis and that, in practice, nearly all patients who are eligible for a tocolytic receive one, the benefit of using atosiban is the placebo-like maternal-fetal side effect profile. These observations support the use of this oxytocin receptor antagonist in the treatment of patients in preterm labor with intact membranes. Efficacy and infant outcome data at <28 weeks are inconclusive.

Double-Blind Method↗
PubMed2000

Are sleep studies worth doing?

AIMS: To evaluate a sleep study service for children suspected of having sleep related upper airway obstruction (SRUAO). DESIGN: Prospective survey. SETTING: Paediatric and ear, nose, and throat clinics of the Royal Free Hampstead NHS Trust. SUBJECTS: Consecutively referred children with SRUAO symptoms. MAIN OUTCOME MEASURES: Sleep study data, referring clinician's impression, and completed symptom questionnaires. RESULTS: A total of 120 children (aged 6 months to 15.5 years) were studied. Study scores showed that 24 were classified as normal, 42 as mild, 33 as moderate, and 21 as severe SRUAO. In the 106 cases with matching data between clinician's impression and study score, 71 had good agreement, 18 were underestimated by the clinician, and 17 were over estimated. No cases reported as moderate or severe sleep apnoea by the study were referred by the clinician as normal. There were no important associations between parental symptom scores and sleep study scores. CONCLUSION: In children with suspected SRUAO, sleep studies do contribute to assessing the need for operation, the likelihood of postoperative respiratory failure, or as a baseline or outcome measure in intervention studies.

Adolescent↗