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Biomedical subjects

J T O'Brien

Publications and source records attributed to J T O'Brien.

89 records · Page 5Linked to original sources
PubMed1991

Effects of tetrahydroaminoacridine on liver function in patients with Alzheimer's disease.

Detailed liver function test analysis is reported for 30 patients with Alzheimer's disease who were treated with tetrahydroaminoacridine. Results show that a benign elevation of aspartate transaminase occurs in up to 50% cases, that the reaction can be a symptomatic one and that clinical hepatitis can occasionally result. Liver function test changes appear dose-dependent and normalize within 2-4 weeks of stopping the drug or of reducing the dose. Women appear more likely to develop hepatotoxicity than men. Rechallenge with THA in patients previously showing abnormalities in liver function shows that some patients are able to tolerate the drug a second time.

Aged↗
PubMed1987

NMR changes in experimental allergic encephalomyelitis: NMR changes precede clinical and pathological events.

In guinea pigs immunized with myelin basic protein (MBP) in complete Freund's adjuvant, experimental allergic encephalomyelitis (EAE) shows a characteristic clinical and pathological course. This study characterized the proton nuclear magnetic resonance (NMR) properties of the central nervous system prior to the onset of clinical signs of EAE. At this time (Days 7-9), the blood brain barrier is disrupted. The effects of the injection of paramagnetic contrast agents gadolinium-DTPA and gadolinium-deferoxamine on the tissue NMR relaxation times were examined. Both proton T1 and T2 relaxation times were prolonged in the spinal cord and the brain prior to the onset of clinical and pathological changes. The largest change was in the thoracolumbar spinal cord where T2 prolongation was 22.9%. Gadolinium-DTPA produced a moderate (5-11%) or marked (9-19%) decrease in control and MBP-treated animals, respectively. Gadolinium-deferoxamine also decreased proton relaxation times but was toxic to all animals, producing respiratory arrest. Changes in proton T2 relaxation times in cord and cerebellum were sufficiently large (greater than 10%) to suggest that they might be visualized by magnetic resonance imaging techniques. We have previously described the changes in proton relaxation times during the acute phase of EAE (S.J. Karlik, G. Strejan, J.J. Gilbert, and J.H. Noseworthy, Neurology 36, 1112 (1986]. This study indicates that proton relaxation times are significantly altered at a time when blood brain barrier disruption occurs prior to the onset of clinical or pathological signs.

Animals↗
PubMed1985

Effect of bepridil in patients with chronic stable angina: results of a multicenter trial.

The effects of bepridil, a calcium antagonist with a half-life of approximately 42 hr, were assessed in a double-blind, randomized, placebo-controlled crossover trial. Forty-four patients (39 men, five women) with exercise-induced angina pectoris and ST segment depression with exercise testing (modified Bruce protocol) were studied. Compared with placebo bepridil (400 mg daily) increased total exercise time, time to onset of angina, time to 1 mm of ST segment depression, time to 2 mm of ST segment depression, and total work achieved (all p less than or equal to .001). Both frequency of angina and nitroglycerin consumption decreased during the bepridil compared with the placebo period (p = .02 and .03, respectively). Minor side effects were noted during both the bepridil and placebo phases. Four patients experienced side effects that limited therapy (dizziness in three and abnormal results of liver function tests in one) and one patient died during the bepridil phase. This study suggests that bepridil, 400 mg daily, is effective for the treatment of exercise-induced myocardial ischemia and angina pectoris.

Angina Pectoris↗
PubMed1984

Effects of bepridil on exercise tolerance in chronic stable angina: a double-blind, randomized, placebo-controlled, crossover trial.

Bepridil, a calcium antagonist with a half-life of approximately 42 hours, was compared with placebo in a double-blind, randomized, crossover trial. Thirteen men (average age 62 years) with exercise-related angina pectoris and a positive exercise test (modified Bruce protocol) were studied. In the group as a whole, bepridil (400 mg once a day) caused an increased total exercise time (2.6 +/- 1.8 minutes, mean +/- standard deviation), time to onset of angina (3.3 +/- 1.6 minutes), time to 1 mm of ST-segment depression (2.2 +/- 2.3 minutes), time to 2 mm of ST-segment depression (2.4 +/- 1.4 minutes) and total work load achieved (1.8 +/- 1.4 kpm) compared with the preceding placebo phase (all p less than 0.05). Frequency of angina and nitroglycerin consumption were low and did not change significantly during bepridil therapy. Comparison of the 3 placebo periods (run-in, double-blind and washout) did not reveal a change in any measurement except time to onset of angina, suggesting no training effect or change in patient status. Adverse effects were common in patients taking both placebo and bepridil, but only 2 patients had adverse effects (dizziness) with bepridil that necessitated discontinuation of therapy. Similarity of the double product (systolic blood pressure X heart rate) at the end of exercise suggests a decrease in myocardial oxygen demand as the primary mode of action. This study suggests that bepridil is a promising agent for the treatment of exercise-induced myocardial ischemia.

Aged↗
PubMed1984

Percutaneous brachial catheterization using a modified sheath and new catheter system.

An alternative method for left heart catheterization via the brachial artery, without cutdown, is described. Percutaneous brachial catheterization was done with a modified 7F side-arm sheath with check valve. A modified 7F high flow catheter was developed employing characteristics of both multipurpose and Sones catheters. The technique was used in 100 patients for left heart catheterization, in patients with and without aortic valve disease, for left ventricular angiography and selective coronary angiography. There were no failures or serious complications. All puncture sites were managed with 15-20 minutes of compression using only a blood pressure cuff or finger pressure. Bleeding was controlled with restoration of the radial pulse in all but one patient, who had severe peripheral brachial atherosclerosis. Cutdown and thrombectomy performed before he left the laboratory using standard catheterization techniques promptly restored blood flow. It is our impression that this technique facilitated outpatient catheterizations, repeat catheterizations at sites of previous cutdowns, and reduced patient discomfort.

Adult↗
PubMed1980

Glucagon kinetics in fasting: physiological elevations in serum 3,5,3'-triiodothyronine increase the metabolic clearance rate of glucagon.

We have attempted to determine if the elevated plasma glucagon concentration and delayed MCR of glucagon (MCRg) observed during caloric restriction are related to the decreased serum T3 that also occurs during fasting. Twelve obese subjects received a 3-h iv glucagon infusion during a 4-day fed period (1000 kCal/day) and again on approximately the third fasting day. Five patients fasted without receiving exogenous T3 (control group), whereas seven subjects fasted but also received 5 micrograms T3 orally every 4 h (T3 group) to maintain approximately the same serum T3 levels in the fed and fasting periods. Glucagon production rates (GPR) were derived by multiplying the MCRg by the respective basal plasma glucogon concentrations. In the control group, the MCRg was 442 +/- 55 ml/m2 . min in the postabsorptive state and decreased to 312 +/- 49 ml/m2 . min (P < 0.025) during fasting, whereas in the T3-treated group, the postabsorptive MCRg was 304 +/- 22 ml/m2 . min and increased during fasting to 417 +/- 47 ml/m2 . min (P < 0.025). The GPRs in the control group were statistically unaltered between the fed (27.7 +/- 3.0 ng/m2 . min) and fasted (22.9 +/- 1.8 ng/m2 . min) intervals, but GPR increased from 37.9 +/- 6.1 ng/m2 . min during fasting to 49.2 +/- 9.1 ng/m2 . min when T3 was administered (5 micrograms every 4 h). The net plasma glucose increment in response to glucagon decreased from 18 mg/dl (fed) to 5 mg/dl (fast) in the control patients and from 10 mg/dl (fed) to 7 mg/dl (fast) in the T3-treated subjects. In the T3-treated patients, serum T3 averaged 124 ng/dl during both feeding and fasting, and rT3 was 55 +/- 6 ng/dl during feeding and 49 +/- 5 ng/dl during fasting. In summary, the results from this study indicate that during fasting 1) slight physiological alterations in serum T3 influence the MCRg, and 2) T3 increases the GPR and blocks the customary fasting-induced rise in rT3. Conceivably, decreased T3 is an early event in the fasting state which serves to decrease the MCRg, a process which subsequently regulates glucose homeostasis.

Adult↗
PubMed1978

Coordinated home care: the Massachusetts General Hospital experience.

The problem of post-hospital care remains a continued challenge, as many patients who no longer require expensive acute care facilities continue to occupy these beds, awaiting appropriate placement. The Massachusetts General Hospital Coordinated Home Care program, under the central administration of the Boston Visiting Nurse Association, has demonstrated that home care can be a viable, economically feasible alternative to institutionalization for carefully selected patients, when the appropriate medical and social needs can be met. Three major groups of patients have been effectively cared for: 1) patients with multi-system chronic illness; 2) patients with terminal malignancies; and 3) patients with catastrophic neurologic disease. The organization of the Coordinated Home Care program, the criteria for patient selection, and the issue of funding are reviewed. The impact of this program is examined in terms of its potential for better utilization of the Massachusetts General Hospital facilities, as well as the more appropriate coordination and use of existing health care resources in the community.

Adolescent↗
PubMedDate not supplied

Medial temporal lobe width on CT scanning in Alzheimer's disease: comparison with vascular dementia, depression and dementia with Lewy bodies.

A simple linear measurement of the minimum width of the medial temporal lobe (MTL) on angled CT scans has been suggested as an accurate ante-mortem marker for Alzheimer's disease (AD). To determine the clinical utility and specificity of this finding, we performed angled CT scans with 5-mm slices in 116 subjects referred to a geographically based Old Age Psychiatry service in Newcastle. Diagnoses were of NINCDS/ADRDA AD (n = 69, 36 probable and 33 possible). NINDS/AIREN vascular dementia (VaD, n = 25), consensus criteria for dementia with Lewy bodies (DLB, n = 9) and DSM-IV criteria for major depression (n = 13). Subjects were well matched for age. Minimum MTL width was significantly greater in depressed subjects (13.7 mm) compared to those with dementia, though no differences were seen within the dementia groups (AD 10.8, VaD 10.4, and DLB 10.9 mm). An MTL width below 11.5 mm had a sensitivity of 54% (56/103) and a specificity of 77% (10/13) for distinguishing dementia from depression. We conclude that a single cross-sectional measurement of MTL width on CT does not help differentiate between different types of dementia, though it may provide some supportive evidence when distinguishing depression from dementia.

Aged↗
PubMedDate not supplied

A comparison of medial and lateral temporal lobe atrophy in dementia with Lewy bodies and Alzheimer's disease: magnetic resonance imaging volumetric study.

OBJECTIVES: To compare medial and lateral temporal lobe atrophy on magnetic resonance imaging (MRI) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), and to examine the relationship between volumetric indices and cognitive and non-cognitive symptoms. METHODS: T(1)-weighted 1.0-tesla MRI scans were acquired in elderly subjects with DLB (n = 26; mean age = 75.8 years) and AD (n = 22; 77.3 years) and normal controls (n = 26; 76.2 years). MRI-based volume measurements of the hippocampus, parahippocampus, fusiform gyrus, combined inferior and middle temporal gyri, and superior temporal gyrus were acquired. RESULTS: Hippocampal and parahippocampal volumes were significantly larger in subjects with DLB compared to AD. Differences in hippocampal volumes between DLB and AD were observed across the entire length, and in all subjects with dementia there was a loss of hippocampal asymmetry compared to normal controls. Atrophy of temporal lobe structures correlated with memory impairment in both groups, and with age in DLB. There was no association between atrophy and psychotic symptoms in either group. CONCLUSIONS: Subjects with DLB and AD have a different pattern of temporal lobe atrophy with the most striking differences relating to medial rather than lateral temporal lobe structures. These structural differences could explain the relative preservation of memory function in DLB compared to AD.

Age Factors↗
PubMedDate not supplied

Imaging of static brain lesions in vascular dementia: implications for clinical trials.

Vascular dementia (VaD) relates to different vascular mechanisms and changes in the brain and has different causes and clinical manifestations, reflecting complex interactions between vascular etiologies, changes in the brain, host factors, and cognition. Critical elements to the concept and diagnosis of VaD are defining the vascular causes, the vascular etiologies, and changes in the brain. Verifying the relation between brain lesions and cognition (i.e., the extent to which brain changes cause, compound, or coexist with cognitive impairment) and establishing the types, extent, side, site, and tempo of brain lesions that relate to incident cognitive impairment are major diagnostic challenges. Previous work on interactions between brain lesion and cognition in to cerebrovascular disease (CVD) have shown variation in the definitions and measures of cognitive impairment, in the techniques and methods used to reveal different brain changes, and in the selection of patient populations. Furthermore, small sample sizes and the absence of multivariate statistics have been design limitations. Accordingly, the different sets of criteria used and methods applied identify different numbers and clusters of subjects and different distribution of brain changes. Furthermore, this heterogeneity is reflected in variation in natural history such as the rate of progression of decline in different cognitive domains over time. All these factors have hampered optimal designs of clinical drug trials. A summary of generalizations regarding lesion and cognition interaction in VaD can be made. (1) Not a single feature, but a combination of infarct features--extent and type of white matter lesions (WMLs), degree and site of atrophy, and host factor characteristics--constitues correlates of VaD. (2) Infarct features favoring VaD include bilaterality, multiplicity (>1), location in the dominant hemisphere, and location in the limbic structures (fronto- and mediolimbic). (3) WML features favoring VaD are extensive WMLs (extensive periventricular WMLs and confluent to extensive WMLs in the deep WM). (4) It is doubtful that only a single small lesion could provide imaging evidence for a diagnosis of VaD. (5) Absence of CVD lesions on computed tomography or magnetic resonance imaging is strong evidence against a diagnosis of VaD. In forthcoming protocols on CVD-associated cognitive impairment, the following brain imaging features should be specified: detailed characterization of brain changes; use of possible predefined subtypes based on brain imaging; use of rating of vascular burden; defining the type and extent of WMLs favoring a diagnosis of VaD; defining the extent of medial temporal lobe atrophy disfavoring a diagnosis of VaD; and technical harmonization of methods of scanning and analysis.

Brain↗