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Biomedical subjects

J Olin

Publications and source records attributed to J Olin.

16 recordsLinked to original sources
PubMed2001

Galantamine for Alzheimer's disease.

BACKGROUND: Galantamine (also called galanthamine, marketed as Reminyl (Janssen)) can be isolated from several plants, including daffodil bulbs, and now synthesized. Galantamine is a specific, competitive, and reversible acetylcholinesterase inhibitor. It is also an allosteric modulator at nicotinic cholinergic receptor sites potentiating cholinergic nicotinic neurotransmission. A small number of early studies showed mild cognitive and global benefits for patients with Alzheimer's disease, and recently several multicentre clinical trials have been published with positive findings. Galantamine has received regulatory approval in Sweden, is available in Austria, and awaits marketing approval in the United States, Europe, and other countries. OBJECTIVES: The objective of this review is to assess the clinical effects of galantamine in patients with probable Alzheimer's disease, and to investigate potential moderators of an effect. SEARCH STRATEGY: The Cochrane Dementia Group specialized register of clinical trials was searched using the terms 'galantamine,' and 'galanthamine' (15 February 2000) as was the Cochrane Controlled Trials Register (2000, Issue 2). These terms were also used to search the following databases: EMBASE, MEDLINE, PsychLit; Combined Health Information Database, NRR (National Research Register), ADEAR (Alzheimer's Disease Education and Referral Centre clinical database, BIOMED (Biomedicine and Health), Glaxo-Wellcome Clinical Trials Register, National Institutes of Health Clinical Trials Databases, Current Controlled Trials, Dissertation Abstracts (mainly North American dissertations) 1961-1994, Index to UK Theses (British dissertations) 1970-1994. Published reviews were inspected for further sources. Additional information was collected from an unpublished investigational brochure for galantamine. SELECTION CRITERIA: Trials selected were randomized, double-blind, parallel-group, and unconfounded comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks in people with Alzheimer's disease. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers and pooled where appropriate and possible. The pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Intention-to-treat and observed cases data were both reported, if the data were available to be reported. -Outcomes of interest include the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), clinical global impression of change (CIBIC-plus or CGIC), Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL), Disability Assessment for Dementia scale (DAD) and Neuropsychiatric Inventory (NPI). - Potential moderating variables of a treatment effect included trial duration and dose. MAIN RESULTS: Seven trials were identified that met criteria for entry, with 6 being Phase II or III industry-sponsored multicentre trials. One was of 12 weeks duration; one of 5 months; one of 29 weeks; and the rest of 6 months duration. Trials of 5 months or more were aggregated in the analyses as '6 months'. Overall, galantamine showed significant treatment effects at daily doses of 16-32 mg/d for trials of 3- to 6-months duration. For global ratings, trials of 3 months duration with doses of 24-32mg/d (Odds Ratio (OR) 2.2; 95%CI 1.4 to 3.7) and 36mg/d (OR 3.3; 95%CI 1.2 to 9.3) were statistically significant in favour of treatment. For trials of 6 months duration (5-months to 29 weeks), only doses of 8mg/d failed to be statistically significant (24mg: OR 2.0; 95%CI 1.5 to2.5; 32mg: OR 1.9; 95%CI 1.4 to 2.5). For cognitive function over 6 months duration: at a 24mg/d, improvements measured -3.5 points (k=3; 95%CI -4.3 to -2.8) on weighted mean difference on the ADAS-Cog scale, and -4.0 points at 32mg/d (k=2; 95%CI -5.0 to -3.0). Both observed cases (WMD 3.8; 95%CI 0.3 to 7.3) and intention to treat analyses using the Disability Assessment of Dementia gave statistically significant results in favour of treatment for daily doses of 32mg for 6 months duration. The small number of trials available for analysis, however, limited the power of analyses to detect differences. Galantamine consistently failed to show statistically significant treatment effects at doses of 8mg/day. Galantamine's adverse effects appear similar to those of other cholinesterase inhibitors, in that it tends to produce gastrointestinal effects acutely and with dosage increases. Overall, people treated with galantamine at doses of 24-32 mg/d were more likely to discontinue participation in most trials than were people treated with lower doses or placebo, but in the one trial with a slower rate of titration the discontinuation rate was not significantly greater than placebo for the 16 mg/day dose. (ABSTRACT TRUNCATED)

Alzheimer Disease↗
PubMed2000

Hydergine for dementia.

BACKGROUND: Currently hydergine is used almost exclusively for treating patients with either dementia, or 'age-related' cognitive symptoms. Since the early eighties there have been over a dozen more clinical trials, yet hydergine's efficacy remains uncertain. Although previous reviews offer generally favorable support for hydergine's efficacy, they were, however, limited by a bias with respect to the particular clinical studies chosen (eg, the inclusion of case reports, and uncontrolled trials), and by authors' impressionistic assessments of results. Not surprisingly, there has been a lack of consensus among reviewers with regard to the efficacy of hydergine. In 1994, a meta-analysis was published by the present reviewers who reported that overall, hydergine was more effective than placebo. However they also observed that the statistical evidence for efficacy in 'possible or probable Alzheimer's disease' patients was so modest that one additional statistically non-significant trial would have reduced the results to non significance. OBJECTIVES: Because of uncertainty surrounding the efficacy of hydergine, the goals of this overview were to assess its overall effect in patients with possible dementia, and to investigate potential moderators of an effect. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'hydergine', 'ergoloids,' 'ergoloid mesylates,' 'dihydroergocristine,' 'dihydroergocryptine,' 'dihydroergotoxine,' and 'dihydroergocornine. MEDLINE, EMBASE, and two proprietary databases were searched also. Published reviews were inspected for further sources. SELECTION CRITERIA: Trials to be included must be randomized, double-blind, parallel-group, and unconfounded comparisons of hydergine with placebo for a treatment duration of greater than 1 week in subjects with dementia or symptoms consistent with dementia. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers, pooled where appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. Outcomes of interest included clinical global impressions of change and comprehensive rating scales. Potential moderating variables of a treatment effect included: inpatient/outpatient status, trial duration, age, sex, medication dose, publication year, and diagnostic grouping. MAIN RESULTS: There were a total of nineteen trials that met inclusion criteria and that had data sufficient for analysis. Thirteen trials reported sufficient information to use a global rating of improvement and nine trials provided information on a comprehensive rating scale. Three trials provided both outcome measures. It was not possible to use many of the published results in a combined analysis owing to the lack of sufficient data to perform statistical analyses. For the twelve trials that used global ratings, there was a significant effect favoring hydergine (OR 3.78, 95%CI, 2.72-5.27). For the nine trials that used comprehensive ratings, there was a significant mean difference favoring hydergine (WMD 0.96, 95%CI, 0. 54-1.37). Hydergine was well tolerated in these trials, with 78% of randomized subjects available for data analyses. Greater effect sizes on global ratings were associated with younger age, and possibly higher dose, although most of the subgroup analyses were statistically insignificant. REVIEWER'S CONCLUSIONS: As in an earlier systematic review, we found hydergine to show significant treatment effects when assessed by either global ratings or comprehensive rating scales (based here on a smaller set of trials than in the earlier published systematic review because trials were required to have data that could conform with MetaView, the Cochrane Collaboration statistics software). The small number of trials available for analysis, however, limited the ability of subgroup analyses to identify statistically significant modera

Aged↗
PubMed2000

Complications associated with the use of urokinase and recombinant tissue plasminogen activator for catheter-directed peripheral arterial and venous thrombolysis.

PURPOSE: Catheter-directed thrombolytic dissolution of peripheral arterial and venous thrombus is in widespread use, yet the frequency and nature of associated complications remain ill defined. In an effort to better characterize the complications associated with urokinase (UK) and recombinant tissue plasminogen activator (rt-PA), the clinical course of patients treated for lower extremity vascular occlusions at a single institution was reviewed. MATERIALS AND METHODS: Over a 9-year period, 653 consecutive patients were treated for lower extremity arterial (527 patients) or venous (126 patients) occlusions with catheter-directed UK (483 patients), rt-PA (144 patients), or both (26 patients). Decisions regarding the choice of thrombolytic agent were made by the clinician. In-hospital complications were subcategorized into hemorrhagic and nonhemorrhagic events and the rate of intracranial hemorrhage was specifically tabulated. RESULTS: There were no significant differences in the demographics or clinical presentation of patients treated with either UK or rt-PA. Bleeding complications occurred less often in the patients treated with UK (insertion site hematoma 21.9% vs. 43.8%, P<.0001, any bleeding necessitating transfusion 12.4% vs. 22.2%, P = .004, and intracranial hemorrhage 0.6% vs. 2.8%, P = .031). Cardiopulmonary complications necessitating transfer to the intensive care unit occurred more frequently in the patients treated with rt-PA (4.9% vs. 1.5%, P = .015). The risk of mortality was not statistically different between the UK and rt-PA treated patients (2.7% vs. 6.2%, P = .221). CONCLUSIONS: Thrombolysis appears safer with UK than with rt-PA, with a lower incidence of hemorrhagic complications. It is possible that this finding is related to differential dosing regimens or intrinsic pharmacologic differences between the agents. The observations of this retrospective analysis require confirmation with a prospective, randomized evaluation.

Arterial Occlusive Diseases↗
PubMed2000

Prognostic indicators in venous ulcers.

BACKGROUND: Venous ulcers can be difficult to heal, and prognostic factors for healing have not been fully elucidated. OBJECTIVE: The objective of this study was to analyze the results of a large multicenter venous ulcer trial to retrospectively establish prognostic factors for venous ulcer healing. METHODS: This study examined data from a previously published prospective randomized placebo-controlled trial of an oral medication versus placebo treatment for venous ulcers. Local leg ulcer care involved the use of a moisture-retentive dressing and sustained graduated compression with a paste bandage and a self-adherent wrap. The oral medication or placebo was administered on a daily basis with the same dressings and bandage system in both groups for 12 weeks. A total of 165 patients completed the full 12-week treatment period; 83 received ifetroban, 82 received placebo. RESULTS: There was no statistically significant difference in outcome between the two groups. The study showed that consistent local ulcer treatment with a clearly defined system of care was associated with an unexpectedly high percentage (55%) of long-standing large venous ulcers (mean duration, 27 months; mean area, 15.9 cm(2)) being healed in both groups. Baseline ulcer area and duration of leg ulcer were found to be important in predicting outcome. Ulcers of short duration were found to be most likely to heal. Percent healing and ulcer area at week 3 were good predictors of 100% healing. Ulcers that had at least 40% healing by week 3 predicted more than 70% of the outcomes correctly. CONCLUSION: From this large study it was determined that baseline ulcer area and ulcer duration are significant predictors of 100% healing and time to heal. Percent healing and ulcer area at week 3 are good predictors of complete ulcer healing. Ulcers that are large, long-standing, and slow to heal after 3 weeks of optimal therapy are unlikely to heal rapidly, and might benefit from alternative therapies.

Double-Blind Method↗
PubMed1995

Public evaluations of unrepresented defendants.

Previous articles have addressed the ethical and legal issues involved when private psychiatrists perform forensic evaluations on criminal defendants before the defendants have access to counsel; but there have been few studies addressing evaluations requested through public facilities and by clinicians other than psychiatrists. The authors present the results of a detailed study of defendants admitted for evaluations of competency to proceed to a forensic inpatient unit in one state, as well as data from a national survey of state forensic facilities. The studies were designed to measure the incidence of unrepresented defendants in a population referred for competency evaluation, as well as to examine the reasons for such occurrences. The data reveal that court-ordered evaluations of unrepresented defendants are rare, but continue to exist.

Commitment of Persons with Psychiatric Disorders↗
PubMed1988

Thrombolysis of peripheral arterial bypass grafts: surgical thrombectomy compared with thrombolysis. A preliminary report.

Twenty-two patients were selected from a group of 33 patients who underwent recombinant human tissue-type plasminogen activator (rt-PA) thrombolysis for thrombosed infrainguinal bypass grafts of the lower extremity and were compared with 38 matched patients who had undergone surgical thrombectomy during the same period. The proportion of persons with diabetes mellitus, smokers, and types of bypass grafts was similar in both groups. More patients in the rt-PA-treated group had hypertension (p = 0.01). To evaluate the different lengths of follow-up, Kaplan-Meier survival analysis was used with a log-rank test to compare the proportion of persons with patent grafts in the two treatment groups. At 30 days, 86% of the rt-PA-treated grafts were still patent compared with 42% of the surgically treated grafts (p = 0.001). When risk factors on the Kaplan-Meier curves were compared, there was no statistical difference with regard to graft patency among the groups. According to simultaneous Cox regression analysis, no risk factor was significantly associated with graft patency. When amputation was evaluated between treatment groups simultaneously with other risk factors in a logistic regression analysis, smoking and age of the graft were marginally significant (p = 0.07), whereas all other factors were clearly not significant. In 91% of the rt-PA-treated patients, a secondary surgical procedure was required to maintain patency of the graft segment. Eighty-nine percent of the surgically treated patients required similar graft revisions. Two patients in the surgical group and one patient in the rt-PA-treated group had major complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

A personal cascade impactor: design, evaluation and calibration.

A cascade impactor has been developed that is suitable for personal sampling. The impactor can be used with four, six, or eight stages with cut points ranging from 0.5 micron to 21 micron aerodynamic diameter. Although the impactor can be operated over a fairly wide flow rate range, it is designed specifically to be operated at 2 L/min so that a personal sampler may be used as the air mover. The nozzles of the impactor are radial slots with six slots per stage for the first six stages. Circular nozzles arranged in a radial pattern are used for the last two stages. On each stage, the area between the nozzles is used as the impaction surface for the stage before it. This design allows for the impactor to be compact, rugged and lightweight (170 gm for the four-stage design). The impactor stages are contained in a mounting bracket that can be clipped to the lapel or pocket. Although the impactor is designed for personal use, it also can be used as a compact impactor for general sampling tasks. The particle cut-off characteristics of each stage and the interstage losses were determined using monodisperse aerosols. The particle losses were found to be low and the cut-off characteristics sharp. Thus, size distributions can be obtained as accurately as with larger cascade impactors.

Air Pollutants, Occupational↗
PubMed1982

The effects of gammahydroxybutyric acid on canine cerebral blood flow and metabolism.

Gammahydroxybutyric acid has been proposed as an alternative to high-dose barbiturate therapy for protecting the brain after ischemic or traumatic insult. The cerebral and systemic metabolic and vascular effects of gammahydroxybutyrate and its lactone analogue, gammabutyrolactone, are addressed in this paper. In anesthetized normal dogs, gammahydroxybutyrate or gammabutyrolactone was infused intravenously at a rate of 1 gm/kg/hr. Cerebral blood flow (CBF) decreased progressively with increasing doses of either agent. Cerebral metabolic rate of oxygen (CMRO2) increased initially with gammahydroxybutyrate, but not following gammabutyrolactone. Reduction in CBF exceeded that of CMRO2 at all doses in both series. The primary systemic effect noted was a severe, lethal metabolic acidosis resulting from infusion of gammabutyrolactone. Gammahydroxybutyrate did not cause a similar acidosis. The imbalance of the CBG-CMRO2 reduction following gammahydroxybutyrate administration suggests that it has no advantage over barbiturates in the management of patients with cerebral vascular insufficiency or intracranial hypertension.

4-Butyrolactone↗
PubMed1976

Cryocrystalglobulinemia.

A 40-year-old woman had cryocrystalglobulinemia with IgG2(K1). To date, 27 other cases of spontaneous crystallization of a plasma protein have been reported. In all, the protein, a cryoglobulin, has been found to be an IgG molecule. The disease most commonly associated with this phenomenon has been multiple myeloma. None of the patients have had Raynaud's phenomenon, but many have had purpuric skin lesions made worse by exposure to cold. In the two cases of essential cryocrystalglobulinemia, crystals were found in the peripheral blood film. Immunologic, biochemical and ultrastructural studies have so far not demonstrated any property common to all cryocrystalglobulins.

Adult↗
PubMedDate not supplied

Psychostimulants for depression in hospitalized cancer patients.

The hospital charts of 59 hospitalized oncology patients who had been treated with either dextroamphetamine or methylphenidate for depression during a 5-year period at the Massachusetts General Hospital were examined. Eighty-three percent of the patients showed at least some improvement following psychostimulant treatment. Seventy-three percent of all patients demonstrated marked or moderate depressive symptom improvement. No significant differences in efficacy were noted between the two psychostimulants, or across psychiatric diagnostic categories for depression. The patients improved quickly, usually within the first 2 days of treatment. Ten percent of the patients experienced adverse reactions warranting discontinuation of the psychostimulants. Fifty-four percent of all patients had some appetite improvement. Anorexia was not observed as a treatment side effect. The authors conclude that psychostimulants are an effective and safe method of treatment for the depressed oncology patient.

Adult↗
PubMedDate not supplied

Intravertebral artery adenosine fails to alter cerebral blood flow in the dog.

The effect of intra-arterial adenosine on cerebral blood flow was studied in 11 anesthetized dogs. In a first group of 6 dogs, adenosine was infused into a vertebral artery for 40 minutes at a dose of 0.3 to 0.5 mg/kg/min. Blood flow was determined before, during and after the adenosine infusion using the radioactive microsphere technique. In a second group of 5 dogs, adenosine (3 +/- 1 mcg/kg/min) was infused in a similar manner after potentiating its effect with intravenous dipyridamole, and measurements before and after the intravenous dipyridamole and during and after the adenosine infusion were performed. Systemic arterial pressure and blood gases were unchanged throughout the experiment in both groups of dogs. Blood flow to the cerebral hemispheres, cerebellum, brain stem, paraspinous and temporalis muscles remained unchanged during the adenosine infusion in both groups of dogs. Adenosine has been implicated as an active agent in the vasodilatory component of cerebral autoregulation. A controversy exists as to whether intervascular or only interstitial adenosine is of physiologic importance. These findings suggest that intra-arterial adenosine does not play a significant role in the regulation of cerebral blood flow.

Adenosine↗