Adverse drug reactions.
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Adverse Drug Reaction Reporting Systems↗
Biomedical subjects
D Homer
Publications and source records attributed to D Homer.
Self-injection of gold and methotrexate.
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Adult↗
Infarct volume as a surrogate or auxiliary outcome measure in ischemic stroke clinical trials. The RANTTAS Investigators.
BACKGROUND AND PURPOSE: Reduction in infarct volume is the standard measure of therapeutic success in animal stroke models. Reduction in infarct volume has been advocated as a biological surrogate or auxiliary outcome measure for human stroke clinical trials to replace or supplement deficit, disability, and global clinical scales. However, few studies have investigated correlations between infarct volume and clinical end points in acute ischemic stroke patients. METHODS: CT scans at days 6 to 11 were acquired prospectively in 191 fully eligible patients enrolled in the Randomized Trial of Tirilazad Mesylate in Patients With Acute Stroke (RANTTAS). Patients were enrolled within 6 hours of onset of stroke in any vessel distribution. Infarct volume was measured by operator-assisted computerized planimetry. RESULTS: One hundred thirty-two patients had visible new supratentorial infarcts, with median infarct volume of 28.0 cm3 (interquartile range, 9.0 to 93.0 cm3). Fifty-nine patients had no visible new infarct. Correlations with standard 3-month outcome scales and mortality were as follows: Barthel Index, r=0.43; Glasgow Outcome Scale, r=0.53; National Institutes of Health Stroke Scale, r=0.54; mortality, r=0.31. For visible infarcts alone, correlations were as follows: BI, r=0.46; GOS, r=0.59; NIHSS, r=0.56; mortality, r=0.32. CONCLUSIONS: Subacute CT infarct volume correlates moderately with 3-month clinical outcome as assessed by widely used neurological and functional assessment scales. The modesty of this linkage constrains the use of infarct volume as a surrogate end point in ischemic stroke clinical trials.
Acute Disease↗
Structural requirements for outside-in and inside-out signaling by Drosophila neuroglian, a member of the L1 family of cell adhesion molecules.
Expression of the Drosophila cell adhesion molecule neuroglian in S2 cells leads to cell aggregation and the intracellular recruitment of ankyrin to cell contact sites. We localized the region of neuroglian that interacts with ankyrin and investigated the mechanism that limits this interaction to cell contact sites. Yeast two-hybrid analysis and expression of neuroglian deletion constructs in S2 cells identified a conserved 36-amino acid sequence that is required for ankyrin binding. Mutation of a conserved tyrosine residue within this region reduced ankyrin binding and extracellular adhesion. However, residual recruitment of ankyrin by this mutant neuroglian molecule was still limited to cell contacts, indicating that the lack of ankyrin binding at noncontact sites is not caused by tyrosine phosphorylation. A chimeric molecule, in which the extracellular domain of neuroglian was replaced with the corresponding domain from the adhesion molecule fasciclin II, also selectively recruited ankyrin to cell contacts. Thus, outside-in signaling by neuroglian in S2 cells depends on extracellular adhesion, but does not depend on any unique property of its extracellular domain. We propose that the recruitment of ankyrin to cell contact sites depends on a physical rearrangement of neuroglian in response to cell adhesion, and that ankyrin binding plays a reciprocal role in stabilizing the adhesive interaction.
Amino Acid Sequence↗
Neuroglian-mediated cell adhesion induces assembly of the membrane skeleton at cell contact sites.
The protein ankyrin links integral membrane proteins to the spectrin-based membrane skeleton. Ankyrin is often concentrated within restricted membrane domains of polarized epithelia and neurons, but the mechanisms responsible for membrane targeting and its segregation within a continuous lipid bilayer remain unexplained. We provide evidence that neuroglian, a cell adhesion molecule related to L1 and neurofascin, can transmit positional information directly to ankyrin and thereby polarize its distribution in Drosophila S2 tissue culture cells. Ankyrin was not normally associated with the plasma membrane of these cells. Upon expression of an inducible neuroglian minigene, however, cells aggregated into large clusters and ankyrin became concentrated at sites of cell-cell contact. Spectrin was also recruited to sites of cell contact in response to neuroglian expression. The accumulation of ankyrin at cell contacts required the presence of the cytoplasmic domain of neuroglian since a glycosyl phosphatidylinositol-linked form of neuroglian failed to recruit ankyrin to sites of cell-cell contact. Double-labeling experiments revealed that, whereas ankyrin was strictly associated with sites of cell-cell contact, neuroglian was more broadly distributed over the cell surface. A direct interaction between neuroglian and ankyrin was demonstrated using yeast two-hybrid analysis. Thus, neuroglian appears to be activated by extracellular adhesion so that ankyrin and the membrane skeleton selectively associate with sites of cell contact and not with other regions of the plasma membrane.
Animals↗
Encopresis: a study of treatment alternatives and historical and behavioral characteristics.
The historical, demographic and pre/post treatment behavioral profiles of a Health Maintenance Organization's (HMO) encopresis patients were studied. The efficacy of two maintenance treatments were also compared. Management included an initial bowel evacuation, high fiber diet, behavior modification program, and random assignment to maintenance on oral laxatives or conditional rectal cathartics. Of the 136 patients evaluated, 61 completed treatment (oral 24; rectal 37). Significant behavioral problems were identified. However, the majority (65%) of patients were managed without psychosocial intervention and successful completion of treatment significantly improved most behaviors. There were no significant differences in efficacy between the oral laxative or conditional rectal cathartic maintenance groups completing treatment. In 87% success continued 6 to 12 months post-treatment.
Administration, Oral↗
Predictors of intracranial carotid artery atherosclerosis. Duration of cigarette smoking and hypertension are more powerful than serum lipid levels.
The effect of cigarette smoking on intracranial internal carotid artery atherosclerosis (ICAS) was studied by obtaining cigarette smoking histories and data on other potential predictors, including serum lipid estimations, for consecutive patients undergoing carotid arteriography. The duration of cigarette smoking was the most significant independent predictor of the presence of ICAS. Other independently significant predictors of ICAS were hypertension, diabetes mellitus, and current systolic blood pressure. The interaction of diabetes and duration of smoking was a significant negative predictor. In patients for whom serum lipid values were available, lower levels of apolipoprotein A-I were associated with a higher risk of having ICAS. However, the effect of apolipoprotein A-I as a predictor of the presence of ICAS was far outweighted by the effects of duration of smoking and hypertension.
Adult↗
Serum lipids and lipoproteins are less powerful predictors of extracranial carotid artery atherosclerosis than are cigarette smoking and hypertension.
The effect of serum lipids and lipoproteins on extracranial carotid artery atherosclerosis (CAS) was studied in patients who underwent carotid arteriography. Serum lipid and lipoprotein values along with data on other potential predictors of extracranial CAS were determined in 240 patients who had at least one extracranial carotid artery visualized. In a multiple logistic regression analysis, the independently significant predictors of the presence of extracranial CAS were, in decreasing order of significance, duration of smoking of cigarettes, hypertension, age, and low-density lipoprotein cholesterol. Serum cholesterol, triglycerides, high-density lipoprotein cholesterol, and apolipoprotein A-I did not show an independent effect. Although low-density lipoprotein cholesterol was an independent predictor of the presence of extracranial CAS, its effect as a predictor was far outweighed by the effects of the duration of smoking of cigarettes and a history of hypertension.
Adult↗
Duration of cigarette smoking is the strongest predictor of severe extracranial carotid artery atherosclerosis.
The effect of cigarette smoking on extracranial carotid atherosclerosis was studies by obtaining cigarette smoking histories and information on other potential risk factors from consecutive patients undergoing carotid arteriography. At least on extracranial carotid artery was visualized in 752 patients in whom the extent of carotid atherosclerosis was assessed. The total years of cigarette smoking was the most significant independent predictor of the presence of severe carotid atherosclerosis. Other independent predictors, in order of significance, were age, hypertension, diabetes mellitus, male sex, and current systolic blood pressure. By age 60 years, the risk of having severe carotid atherosclerosis for a person who had smoked for 40 years was approximately 3.5 times that for a never smoker. The major benefit of smoking cessation is in limiting the accumulation of smoking years.
Age Factors↗
Predictive value of carotid bruit for carotid atherosclerosis.
To assess the predictive value of carotid bruit for moderate-to-severe carotid atherosclerosis, the results of carotid arteriograms performed on 1004 subjects were correlated with the findings of auscultation of the carotid arteries. Predictive values of carotid bruit for ipsilateral extracranial carotid atherosclerosis were 77% for localized bruits and 74% for diffuse bruits. The predictive values of extracranial carotid bruit for ipsilateral intracranial carotid atherosclerosis were 16% for localized bruits and 18% for diffuse bruits. Assessing both carotid arteries together, the predictive value of carotid bruit for moderate-to-severe atherosclerosis at any extracranial carotid site was 85%, there being no difference whether the bruits were diffuse, localized, bilateral, or unilateral. Diffuse or localized bruits, whether unilateral or bilateral, are equally predictive of moderate-to-severe atherosclerosis in the extracranial carotid artery, but both are poor predictors of intracranial carotid artery disease.
Adult↗
Cerebral vasospasm and eclampsia.
We describe a patient who experienced focal cerebral and brainstem ischemia in the setting of postpartum eclampsia. Cerebral angiography showed spasm of large- and medium-caliber arteries. This case provides rare documentation that vasospasm may account for cerebral ischemia in eclamptic women with focal signs. This observation suggests that in such patients cerebral angiography may be informative and useful.
Adult↗
Trends in the incidence rates of stroke in Rochester, Minnesota, since 1935.
The Mayo Clinic medical records system and records-linkage system have been used to study trends in the incidence of stroke in Rochester, Minnesota, for comparison with U.S. stroke mortality trends. This study extends the observations back through 1935. The average annual incidence rate for the period 1935 to 1944 was 188 and 179 per 100,000 population for men and women, respectively--not significantly different from 200 for men and 178 for women for the period 1945 to 1954. The blood pressure level in these patients did not affect probability of survival or recurrent stroke. The trend in the incidence rate of stroke for women showed no change for the 20 years from 1935 to 1954, after which there was a gradual decline. For men there was little change until 1969, after which there was a sharp decline. We suggest that the gradual decline in U.S. stroke mortality rates for this early period may include an artifact introduced by changing codes and changing fashions of diagnosis.
Blood Pressure↗
Exposure of the major human red-cell glycolipid, globoside, to galactose oxidase.
Plasma membrane glycolipids are localized at the outer leaflet of the lipid bilayer, and their carbohydrate portions are exposed to the environment. The efficiency of exposure has, however, not been known. We have been able to determine the availability of the major red cell glycolipid, globoside, to externally added galactose oxidase. Red cells were extensively treated with the enzyme and the oxidized cells reduced with NaBD4. After isolation the extent of exposed globoside was estimated by mass spectrometry. The results show that the exposure of globoside varies in red cells of different individuals from 37-66%. The fatty acid composition of externally available globoside was the same as that of non-oxidized globoside. The exposure was not influenced by protease treatment of intact cells and no correlation was found with different ABO blood groups.
Borohydrides↗
Vitamin A and its transport proteins in patients with chronic renal failure receiving maintenance haemodialysis and after renal transplantation.
Serum vitamin A, retinol binding protein, prealbumin and transferrin have been studied in chronic renal failure patients receiving maintenance haemodialysis and after renal transplantation. Vitamin A and retinol binding protein were uniformly raised in haemodialysis patients and this was unrelated to the period on dialysis. There was a molar excess of retinol binding protein to both vitamin A and prealbumin as compared with normal individuals. Renal transplantation significantly reduces serum vitamin A and retinol binding protein concentrations but has no effect on prealbumin concentrations. The reduction in vitamin A and retinol binding protein is variable in individual patients and cannot be predicted either by the allograft function or time since transplantation. Several years after transplantation, with normal serum creatinine, both serum vitamin A and retinol binding protein levels may still be greatly increased. Despite the very high vitamin A and retinol binding protein concentrations, the close correlation between the two seen in normal individuals is well maintained. The continuing high vitamin A and retinol binding protein levels in patients with satisfactorily functioning transplants is unexplained.
Creatinine↗
High-b-value diffusion-weighted MR imaging of suspected brain infarction.
BACKGROUND AND PURPOSE: Recent technological advances in MR instrumentation allow acquisition of whole-brain diffusion-weighted MR scans to be obtained with b values greater than 1,000. Our purpose was to determine whether high-b-value diffusion-weighted MR imaging improved contrast and detection of signal changes in acute and chronic brain infarction. METHODS: We prospectively evaluated the MR scans of 30 subjects with a history of possible brain infarction on a 1.5-T MR imager with 40 mT/meter gradients (slew rate 150 T/m/s) by use of the following single-shot echo-planar diffusion-weighted MR sequences: 1) 7,999/ 71.4/1 (TR/TE/excitations, b = 1,000; 2) 999/ 88.1/3, b = 2,500; and 3) 7,999/ 92.1/4, b = 3,000. Diffusion-weighted MR imaging was performed in three orthogonal directions during all sequences. All subjects were scanned with fast fluid-attenuated inversion recovery (FLAIR) (10,006/145/2,200/1 [TR/TE/TI/excitations]) and fast spin-echo T2-weighted (3,650/95/3 [TR/TE/excitations], echo train length, 8). The diagnosis of brain infarction was established by clinical criteria. RESULTS: Twenty women and 10 men with a mean age of 67.7 years were enrolled in the study. One subject was excluded owing to poor image quality. Twelve of 29 subjects had a clinical diagnosis of acute infarction. All 12 had lesions that were hyperintense on diffusion-weighted images at all three b values; five were cortical and seven subcortical. There was increased contrast of all lesions on high-b-value scans (b = 2,500 and 3,000). Lesions that were hypointense on diffusion-weighted images were identified and evaluated at the three different b values. At b = 1,000, there were 19 hypointense lesions, whereas at b = 2,500 and 3,000 there were 48 and 55 lesions, respectively. On FLAIR and T2-weighted images, these low-signal lesions were predominantly chronic, subcortical, ischemic lesions and lacunar infarcts, but four chronic cortical infarcts, one porencephalic cyst, and one primary brain tumor were also found. Low-signal lesions were also noted to have increased contrast on high-b-value diffusion-weighted scans. CONCLUSION: High-b-value diffusion-weighted MR imaging (b = 2,500 or b = 3,000) had no impact on diagnosis of acute infarction. High-b-value diffusion-weighted MR imaging (b = 2,500) combined with diffusion-weighted MR imaging at b = 1,000 improves tissue characterization by increasing the spectrum of observed imaging abnormalities in patients with suspected brain infarction.
Aged↗