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Biomedical subjects

R Sloan

Publications and source records attributed to R Sloan.

At least 19 recordsLinked to original sources
PubMed2002

Benzodiazepines and related drugs for insomnia in palliative care.

BACKGROUND: Insomnia, a subjective complaint of poor sleep and associated impairment in daytime function, is a common problem. Currently, benzodiazepines are the most used pharmacological treatment for this complaint. They are considered helpful for occasional short-term use up to four weeks but longer term use is not advised due to potential problems regarding tolerance, dosing escalation, psychological addiction and physical dependence. There is no consensus on their utility in patients with progressive incurable conditions who may require assistance with sleep for many weeks as their condition deteriorates. OBJECTIVES: To assess the effectiveness and safety of benzodiazepines or benzodiazepine receptor agonists such as Zolpidem, Zopiclone and Zaleplon for insomnia in palliative care. SEARCH STRATEGY: Several electronic databases were searched including Cochrane PaPaS Group specialized register, Cochrane Library Issue 4, 2001, MEDLINE, EMBASE, BNI plus, CINAHL, BIOLOGICAL ABSTRACTS, PSYCINFO, CANCERLIT, HEALTHSTAR, WEB OF SCIENCE, SIGLE, Dissertation Abstracts, ZETOC and the MetaRegister of ongoing trials. These were searched from 1960 to 2001 or as much of this range as possible. Additional articles were sought by handsearching reference lists in standard textbooks and reviews in the field and by contacting academic centres in palliative care and pharmaceutical companies. There were no language restrictions. SELECTION CRITERIA: Studies considered for inclusion were randomized controlled trials of adult patients in any setting, receiving palliative care or suffering an incurable progressive medical condition. (For example, cancers, AIDS, Motor Neurone Disease, Multiple Sclerosis, Parkinson's Disease, Chronic Obstructive Pulmonary Disease). There had to be an explicit complaint of insomnia in study participants, diagnosed by any of the three main classification systems (DSM-IV (APA 1994), ICSD (AASD 1990) or ICD (WHO 1992)), or as described in the study if it involved a subjective complaint of poor sleep. Studies had to compare a benzodiazepine or Zolpidem or Zopiclone or Zaleplon with placebo or active control for the treatment of insomnia. Any duration of therapy were considered. DATA COLLECTION AND ANALYSIS: Abstracts were independently inspected by both reviewers, full papers were obtained where necessary. Where there was uncertainty advice was sought by a third (PW). Data extraction and quality assessments were undertaken independently by both reviewers. MAIN RESULTS: No randomized controlled trials were identified meeting the a priori inclusion criteria. Thirty-seven studies were considered but all were excluded from the review. REVIEWER'S CONCLUSIONS: Despite a comprehensive search no evidence from randomized controlled trials was identified. It was not possible to draw any conclusions regarding the use of benzodiazepines in palliative care.

Benzodiazepines↗
PubMed2001

Relationship between serum levels of IL-10, MRI activity and interferon beta-1a therapy in patients with relapsing remitting MS.

BACKGROUND: The purposes of this study were to: (1) compare monthly serum IL-10 in patients with relapsing remitting (RR) multiple sclerosis (MS) and healthy controls, (2) determine the relationship between IL-10 and MRI activity and (3) determine the effect of interferon beta-1a (IFNB-1a) treatment on IL-10 levels. RESULTS: Median serum IL-10 levels were lower in untreated RRMS (185.5 pg/ml) compared to controls (438.5 pg/ml) (P=0.19). Serum levels of IL-10 did not appear to predict the appearance of new gadolinium-enhancing (Gd+) lesions concurrently or 1 month thereafter. However, IL-10 levels were more likely to be elevated the month during which Gd+ lesions resolved (OR=3.14, P=0.01). Median IL-10 levels were lower during IFNB-1a treatment (P=0.01). CONCLUSIONS: These observations suggest a relationship between serum IL-10 levels and resolution of abnormal vascular permeability in new lesions.

Adolescent↗
PubMed2000

A longitudinal study of ventricular volume in early relapsing-remitting multiple sclerosis.

The specific aim of this study was to determine whether progressive brain atrophy could be detected within 18 months of establishing a diagnosis of relapsing-remitting multiple sclerosis (RRMS). Fifteen patients with clinically definite RRMS (mean disease duration from first symptom=6 months, mean EDSS=1.2) completed 6 - 14 monthly quantitative MRI sessions. The volume of the lateral ventricles was determined each month using a semi-automated thresholding technique from T1-weighted axial images. The number of new monthly gadolinium-enhancing (Gd+) lesions and EDSS scores were also recorded. Lateral ventricular volumes increased significantly during this study. When individual data were examined, statistically significant changes were observed in six of 15 patients. Monthly change in ventricular volume was related to baseline EDSS and total number of new Gd(+) lesions. These observations indicate brain atrophy, a putative imaging marker of diffuse demyelination and axonal loss, can occur as early as 18 months after first symptoms of RRMS, and is related to the baseline level of disability and to the number of new Gd+ lesions. Multiple Sclerosis (2000) 6 332 - 337

Adolescent↗
PubMed1999

Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis.

OBJECTIVE: To 1) compare monthly serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-type 1 (TIMP-1) in patients with relapsing-remitting MS (RRMS) versus healthy controls and 2) determine the relationship among monthly serum levels of MMP-9 and TIMP-1 and MRI activity. BACKGROUND: Activated T-cells and macrophages secrete MMPs that may facilitate their migration across vascular subendothelial basement membranes into the CNS. The serum concentration of MMP-9 is reported to be higher in patients with RRMS than healthy controls. METHODS: Monthly evaluations including gadolinium-enhanced (Gd+) brain MRI and measures of serum MMP-9 and TIMP-1 were performed for up to 15 months in 24 patients with RRMS and for up to 4 months in 10 controls. RESULTS: Serum MMP-9 but not TIMP-1 levels are elevated in RRMS patients compared to healthy controls (p = 0.025, p = 0.61). In a univariate analysis, high MMP-9 and low TIMP-1 levels precede appearance of new Gd+ lesions (respectively; odds ratio = 3.3, p = 0.008; odds ratio = 2.2, p = 0.086). In a multivariate analysis, in comparison to months when MMP-9 is low and TIMP-1 high, MRI scans obtained the month following high MMP-9 and low TIMP-1 serum concentrations are more likely to report new Gd+ lesions (p = 0.0006, odds ratio = 21.5). CONCLUSION: An increase in the activity of matrix metalloproteinase-9 (MMP-9) relative to tissue inhibitor of MMP-type 1 (TIMP-1) may be related to formation of new MS lesions, suggesting that serum levels of MMP-9 and TIMP-1 may be surrogate markers of disease activity in relapsing-remitting MS.

Adolescent↗
PubMed1999

A pilot study of MRI activity before and during interferon beta-1a therapy.

We compared the number of new gadolinium-enhancing and T2-weighted lesions on six monthly MRI scans in eight patients with relapsing multiple sclerosis before and during treatment with weekly intramuscular interferon beta-1a (Avonex; 30 microg). MRI activity was modestly reduced during treatment (p = 0.016). The treatment effect was also significant after adjusting pretreatment lesion frequency for regression to the mean. Based on this pilot study, Avonex, as approved for treatment of relapsing forms of MS in the United States, reduces new MRI activity.

Adult↗
PubMed1999

[Effect of weekly intramuscular interferon beta-1a on MRI lesions in patients with relapsing multiple sclerosis].

We compared the number of new gadolinium-enhancing (Gd+) and T2-weighted (T2W) lesions on 6-monthly MRI scans before and after initiating weekly intramuscular injections of interferon beta-1a (Avonex) 30 mcg. The mean number of new focal Gd+ lesions detected during the 6 monthly on-treatment scanning sessions was 58 per cent less per MRI scan and 62.5 per cent less per patient than during the 6 monthly pre-treatment scanning sessions (p = 0.016, Wilcoxon signed rank test). The results are similar for new focal Gd+ and T2W lesions. The reduction in disease activity detected by monthly Gd+ enhanced MRI scans after initiating weekly intramuscular interferon beta-1a 30 mcg is consistent with benefits observed with thrice weekly subcutaneous interferon beta-1a 10 and 30 mcg and alternate day subcutaneous interferon beta-1b 8.0 MIU.

Adjuvants, Immunologic↗
PubMed1998

Breaking the news in amyotrophic lateral sclerosis.

Telling the diagnosis to patients with amyotrophic lateral sclerosis (ALS) is a daunting task for any neurologist. Obviously, breaking the news in ALS is not a standardizable procedure. However, proven techniques exist to reduce the trauma to the patient and ease the burden on the doctor, thus reducing the risk of burnout and the tendency to 'pull away' from the patient. Such communication skills are of fundamental importance to clinical practice and should be more prominent in medical teaching. The way the patient is told the diagnosis is now recognized to be the first and one of the most delicate steps in palliative care. Information is best offered in a stepwise fashion at the patient's pace with an emphasis on positive aspects, and in the presence of the patient's family. Reviewing available therapeutic options and current research efforts may foster hope for the future, while pointing out that almost all symptoms of ALS can be alleviated by palliative therapy may help to reduce fears. Encouraging patients to ask questions and disclose anxieties is important for their psychological wellbeing. Available options for mechanical ventilation should be reviewed early enough to allow for unhurried decision-making. We believe that the terminal phase of the disease should be discussed at the latest when dyspneic symptoms appear, in order to prevent unwarranted fears of 'choking to death'.

Amyotrophic Lateral Sclerosis↗
PubMed1998

A serial study of new MS lesions and the white matter from which they arise.

OBJECTIVE: To compare MS normal-appearing white matter (NAWM) where new gadolinium-enhancing (Gd+) lesions do and do not arise. METHODS: A total of 22 relapsing-remitting MS patients and 11 healthy control subjects completed as many as 12 monthly brain MRI sessions. Quantitative measures of gadolinium enhancement (GDR), water proton density (PDN), water proton T2 relaxation time constants (T2), magnetization transfer ratio (MTR), and T1-weighted signal intensity (T1N) were followed serially in healthy control and MS NAWM. RESULTS: A total of 129 new Gd+ lesions were identified in 11 patients. PDN, T2, MTR, and T1N were diffusely abnormal in MS NAWM. NAWM regions in which new Gd+ lesions arose have increased GDR, PDN, and T2, and reduced MTR and T1N compared with contralateral homologous NAWM regions in which no new Gd+ lesions arose. Differences between these NAWM regions preceded lesion appearance for at least several months. After lesions became visible, GDR returned to baseline within 2 months, and PDN and MTR had larger residual abnormalities than T2 or T1N. CONCLUSIONS: Quantitative MRI measures are diffusely abnormal in MS NAWM. These measures are, on average, more abnormal in NAWM regions in which new Gd+ lesions arise. After the appearance of Gd+ lesions, measures of PDN and MTR may provide more appealing markers of relatively irreversible tissue damage than measures of T2 and T1N.

Adult↗
PubMed1997

Pharmacokinetics of oral glyburide in subjects with non-insulin-dependent diabetes mellitus and renal failure.

To test the hypothesis that renal failure has no effect on the pharmacokinetics of glyburide, five subjects with non-insulin-dependent diabetes mellitus (NIDDM) and end-stage renal disease requiring hemodialysis, and four NIDDM subjects with normal renal function were studied. On days 0, 1, and 15, subjects consumed 33 carbohydrate grams, and glucose, insulin, and C-peptide were measured for 4 hours. On day 1, subjects received 3 mg glyburide and measured plasma concentrations for 48 hours. On day 3, multiple dosing on 3 mg glyburide daily began. On day 15, plasma concentrations were measured for 48 hours. The pharmacokinetics and pharmacodynamics of glyburide, glucose, insulin, and C-peptide were determined as well as daily fasting blood glucose. Glucose area under the curve (AUC) and daily fasting glucose levels did not change in either controls or hemodialysis subjects. The mean serum glyburide blood levels and pharmacokinetics did not differ after initial or chronic glyburide administration in NIDDM subjects with end-stage renal disease treated with hemodialysis compared with controls. Glyburide half-life averaged 3.3 hours in control subjects and 5.0 hours in hemodialysis subjects. Hemodialysis subjects had increased C-peptide and insulin AUC with chronic dosing. Renal failure does not affect the pharmacokinetics of 3.0 mg oral glyburide.

Administration, Oral↗
PubMed1996

Neurologic Manifestations of HIV Infection Without AIDS:Follow-UP of a Cohort of Homosexual and Bisexual Men.

To identify neurological abnormalities in HIV infection, 159 HIV-seropositive men without AIDS and 76 seronegative controls underwent standardized general and neurological examinations, lumbar puncture (LP), neuropsychological (NP) assessment, and brain magnetic resonance (MR) imaging. History, physical, and laboratory evaluations were repeated every six months. NP tests (all subjects) and MR imaging (seropositives only) was repeated every 6-12 months; LP (seropositives only) was repeated yearly. Mean follow-up was 24.6 months. Neurological abnormalities, most related to hearing, were seen in 60 (38.2%) of 157 seropositives and 23 (30.3%) of 76 controls at baseline (p = NS). During follow-up, 43 (31.6%) of 136 seropositives had persistent hearing abnormalities compared to 9 (14.1%) of 64 seronegatives (p = 0.008). Seven HIV-seropositives developed peripheral neuropathy; this was more common among those with hearing abnormalities (p = 0.03). HIV-seropositives performed less well on NP tests than controls, but overall performance did not decline. Worsening brain atrophy by MR imaging or cerebrospinal fluid abnormalities are more common in HIV-seropositives than seronegatives and may share a common mechanism with peripheral neuropathy. Further study is needed to determine whether these abnormalities portend more serious neurological disease.

Acquired Immunodeficiency Syndrome↗
PubMed1995

An improved glomerular filtration rate in cardiac transplant recipients with once-a-day cyclosporine dosing.

We tested the hypothesis that there would be a difference in the unwanted side effects of cyclosporine (CsA) when heart transplant patients received CsA once a day versus half the dose twice a day. Eight stable cardiac transplant patients (> 6 months posttransplant) were administered their dose of CsA either as a once-a-day dose or half the dose b.i.d. for 21 days in a random fashion. After 21 days the patients were crossed over to the other regimen. Patients underwent inulin and PAH clearances at CsA trough on each arm of the study. Each patient collected several 24-hr urines for determination of creatinine clearance, and had ambulatory blood pressure monitoring done during each arm of the study. Serum chemistries and lipid profiles were performed at the end of each arm of the study. The CsA dose was 1.9-7.2 mg/kg/day. All patients were hypertensive and on calcium channel antagonists. Once-a-day CsA dosing resulted in a 29% decrease in trough CsA levels. A significant increase in glomerular filtration rate, as estimated by the clearance of inulin, (65.16 +/- 24.4 q. day vs. 54.62 +/- 19.0 b.i.d. (ml/min) P < .02) and a significant increase in renal plasma flow, as estimated by the clearance of PAH, occurred with once-a-day dosing when compared with b.i.d. dosing (P = .02). Creatinine clearances were not different between the 2 arms of the study and significantly overestimated glomerular filtration rates (P = .01). CsA dosing b.i.d. resulted in significantly higher nocturnal blood pressures (91.2 +/- 8.3 b.i.d. vs. 86.4 +/- 8.1 q. day, mmHg, P = .015) when compared with once-a-day dosing. A significant increase in LDL cholesterol and a significant decrease in HDL cholesterol were noted during the b.i.d. dosing arm when compared with q. day CsA dosing. We conclude that in stable heart transplant patients once-a-day CsA dosing results in better GFR and renal plasma flow, a lower nocturnal blood pressure, and an improved lipid profile when compared with dosing CsA twice a day.

Blood Pressure↗