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Biomedical subjects

R D Brown

Publications and source records attributed to R D Brown.

At least 109 records · Page 6Linked to original sources
PubMed1998

Stroke-attributable nursing home use: a population-based study.

OBJECTIVE: To estimate 1) among patients with stroke, nursing home use attributable to stroke, and 2) the savings in nursing home use, assuming strokes were prevented. METHODS: All confirmed cases of first stroke among Rochester, Minnesota, residents from 1987 through 1989 (n = 290) and one nonstroke control of same gender and similar age for each patient were followed up in provider-linked medical records and State of Minnesota nursing home files until emigration, death, or December 31, 1994. Data included disability and place of residence at baseline (i.e., date of stroke for each patient and their corresponding control), length of follow-up, cumulative incidence of nursing home admission, proportion of follow-up spent in a nursing home, and number of nursing home days. RESULTS: Before baseline, patients and controls were similar in the level of disability (mean Rankin = 1.7 for patients and 1.6 for controls) and the proportion in a nursing home (11% for both groups). Among those not in the nursing home at baseline, 5-year cumulative incidence of first admission was 48% for cases versus 20% for controls. Survival was significantly shorter for cases than for controls; the proportion of follow-up spent in the nursing home was 20% for cases versus 11% for controls. When controlling for survival, cases experienced an average of 110 (95% CI, 63 to 156) more nursing home days per person than controls in the first five years. When nursing home use during differential survival was included, the difference in nursing home days between cases and controls was no longer significant (p = 0.16). CONCLUSIONS: Stroke prevention would result in fewer cases admitted to the nursing home, older age at first admission, and a smaller proportion of remaining life spent in the nursing home, but stroke prevention would not result in fewer nursing home days.

Aged↗
PubMed1998

Incidence and prevalence of intracranial aneurysms and hemorrhage in Olmsted County, Minnesota, 1965 to 1995.

BACKGROUND: There are no previous reports of the incidence rate of intracranial saccular aneurysms in a defined population. METHODS: Medical records of all residents of Olmsted County, MN, with a possible intracranial saccular aneurysm (IA) were reviewed. Incidence rates and prevalence of symptomatic and asymptomatic IAs, aneurysmal intracranial hemorrhage (ICH), and frequency of IA detection based on size and site were determined. RESULTS: A total of 348 IAs were detected among 270 persons during the 31-year period from 1965 to 1995, including 188 symptomatic patients at presentation (166 with ICH). The age- and sex-adjusted incidence rate for IAs excluding asymptomatic autopsy cases was 9.0/100,000 person-years (P-Y; 95% CI, 7.8 to 10.2). The rate of detection in women (10.7/100,000 P-Y; 95% CI, 8.9 to 12.4) was higher than in men. The highest incidence of IA was among those age 55 to 64 years in men, and 65 to 74 years in women. The incidence rate of aneurysmal ICH was 6.9/100,000 P-Y (95% CI, 5.9 to 8.0). Aneurysms were seven times more likely to be detected in the anterior circulation, and this ratio was not altered significantly by age or gender. On January 1, 1990, the age- and sex-adjusted prevalence rate of identified IAs was 83.4/100,000 population (95% CI, 64.1 to 102.7). CONCLUSIONS: This study provides unique data on the population-based incidence and prevalence rates of IAs.

Adolescent↗
PubMed1998

The expression of T cell related costimulatory molecules in multiple myeloma.

Presentation of tumour antigen by malignant cells not expressing costimulatory molecules is considered to be a major cause of the failure of the host's immune response against tumours. This study has determined the expression of the B7 family of costimulatory molecules on malignant plasma cells and the expression of the counter receptor molecules, CD28 and CD152 (CTLA-4), on T cells of patients with multiple myeloma. CD28 expression was present on most CD4 cells but was lower on CD8 cells especially from those patients who also showed evidence of expanded T cell clones (median 40%. z=2.4; p<0.02). CD152 expression was increased in 50% (9/18) of patients with myeloma. CD80 (B7-1) expression was present on the plasma cells of only 1 of 27 samples but CD86 (B7-2) expression within the normal range was present on the plasma cells of 14 of 27 samples. Primitive plasma cells (CD38++ CD45++) had a higher expression of CD86 (median 78%) than mature plasma cells (CD38++ CD45-) (median 19%, z=3.7; p<0.01). Thus patients with expanded T cell clones have a downregulated T cell CD28 expression and lack B7-1 expression on their malignant plasma cells. These results are consistent with the concept that engagement of the T cell receptor by tumour antigen on B7-1 deficient malignant plasma cells would result in T cell anergy rather than productive immunity.

Abatacept↗
PubMed1998

MR angiographic and sonographic indications for endarterectomy.

PURPOSE: Our objective was to determine whether appropriate criteria could be developed for performing an endarterectomy on the basis of sonographic and MR angiographic findings. METHODS: Fifty patients were examined prospectively with sonography, MR angiography, and conventional angiography. All three imaging studies were performed within 2 weeks of one another, and conventional angiography served as the reference standard. RESULTS: All 10 carotid occlusions were detected with sonography and MR angiography. Sonography accurately showed flow in two arteries, and MR angiography showed flow in one of three nearly occluded arteries with extremely slow flow. Multislab three-dimensional time-of-flight MR angiographic sequences underestimated the degree of stenosis in 12 arteries, and in two cases this resulted from high T1 signal within the atherosclerotic plaque. With conventional angiography as the reference standard for 70% to 99% stenosis, sonography had a sensitivity of 96%, a specificity of 91%, and a positive predictive value of 90%, while concordant sonographic findings and the presence of a signal void on multislab 3-D time-of-flight sequences had a sensitivity of 72%, a specificity of 98%, and a positive predictive value of 97%. CONCLUSION: Endarterectomy performed on the basis of sonographic findings of 70% to 99% stenosis and of a signal void on multislab 3-D time-of-flight MR angiographic sequences is appropriate.

Adult↗
PubMed1998

Pharmacological and immunocytochemical characterization of subtypes of alpha-1 adrenoceptors in dog aorta.

In this study, the effects of nine alpha-1 adrenoceptor antagonists [prazosin, WB 4101 (WB), chloroethylclonidine (CEC), 5-methylurapidil (5-MU), BMY 7378 (BMY), MDL 73005EF (MDL73), MDL 72832 (MDL72), RS 17053 (RS) and SK&F 105854 (SKF)] were studied on contractile responses to phenylephrine (PE) of the endothelium-denuded dog aorta in vitro. All antagonists, except CEC, 5-MU and RS, produced concentration-dependent competitive inhibition of contractile responses of the aorta to PE. The rightward shift of the concentration-response curves of PE yielded constant pKB values with increasing antagonist concentrations in most cases allowing a single pooled value to be determined: for prazosin, a pKB of 8.99 +/- 0.11 (n = 20, KB of 1.03 nM); for WB, a pKB of 8.75 +/- 0.08 (n = 23, KB of 1.76 nM); for BMY, a pKB of 7.21 +/- 0.13 (n = 13, KB of 62 nM); for MDL72, a pKB of 7.95 +/- 0.15 (n = 12, KB of 11.2 nM); and for SK&F 105854, a pKB of 5.82 +/- 0.08 (n = 15, KB of 1.52 microM). For MDL73, pKB values decreased with antagonist concentration: 7.88 +/- 0.06 at 10 nM, 7.56 +/- 0.28 at 100 nM and 6.92 +/- 0.18 at 1000 nM, which suggests the presence of more than one receptor subtype. CEC (10 and 100 microM) almost completely inhibited responses to PE; lower concentrations had no significant effect. 5-MU (10-300 nM) and RS (3-300 nM) were ineffective antagonists in this tissue. Because WB, a highly selective alpha-1D and alpha-1A adrenoceptor subtypes inhibitor, blocked PE responses (with less affinity than for alpha-1A adrenoceptors), and 5-MU and RS, which are selective blockers for alpha-1A adrenoceptor, were ineffective, we conclude that alpha-1A adrenoceptors are absent in the dog aorta. The effects of the less selective MDL72 were inconsistent with actions at alpha-1B or alpha-1D adrenoceptors. Although WB shifted the PE concentration-response curve to the right, the abilities of BMY, MDL73 and SKF to inhibit competitively PE contraction were of lower affinity compared with expectations for interaction with alpha-1D adrenoceptors; they are not the predominant subtype. The complete inhibition of PE responses by CEC suggests that the dog aorta contains the alpha-1B adrenoceptor subtype. In immunocytochemical studies of the expression of alpha-1B adrenoceptor, all cells apparently expressed this protein. Moreover, Western blot studies of the microsomal fractions confirmed the presence of alpha-1B adrenoceptors. In the dog aorta, the alpha-1 adrenoceptors predominantly resemble alpha-1B rather than alpha-1D adrenoceptors as reported in the rat aorta.

Animals↗
PubMed1998

Physical play and cognitive development: integrating activity, cognition, and education.

We propose that humans may have evolved a special sensitivity to certain types of social information during rough-and-tumble play that facilitates social cognition. The cognitive benefits of physical play are described as providing a break from demanding intellectual tasks, and are hypothesized to be related to gender differences in spatial cognition.

Adolescent↗
PubMed1997

Designing combinatorial library mixtures using a genetic algorithm.

The design of combinatorial mixture libraries should take account of a number of factors. This paper describes the application of a genetic algorithm to optimizing the diversity of libraries while minimizing the effort that will be needed to deconvolute the biological hits by mass-spectroscopic techniques. It differs from previous applications of genetic algorithms to combinatorial library design in that each chromosome encodes an entire library with the result that properties of the library are optimized. Our method is such that it is easily extensible to optimizing the distributions of any number of physical or other properties of the library. The method allows for the combinatorial constraint inherent in mixtures that every substituent at each diversity site must occur in combination with every substituent at every other site. We present results showing that the genetic algorithm can produce good library designs in timely manner.

Algorithms↗
PubMed1997

Prognostic significance of DNA ploidy and proliferation in 309 colorectal carcinomas as determined by two-color multiparametric DNA flow cytometry.

BACKGROUND: Although DNA flow cytometry has been shown to be of independent value in determining the prognosis of colorectal carcinoma, a number of well-designed studies with contradictory findings have left unresolved the clinical significance of DNA ploidy and proliferation in biologically meaningful subsets of colorectal carcinoma cases. METHODS: To evaluate the prognostic significance of DNA ploidy and proliferation as determined by flow cytometry in a prospective series of 309 human colorectal carcinomas with 4-6 years of follow-up, fresh tumors were mechanically dissociated into whole cell suspensions and dual fluorescence-labeled to allow gated analysis of subpopulations with phenotypic markers. Software programs with histogram-dependent algorithms employing background, aggregate, and debris correction were used in DNA and cell cycle quantitation. Data were analyzed according to recommendations of the 1992 DNA Flow Cytometry Consensus Conference. RESULTS: None of the clinical, site, or staging parameters, including TNM stage variables, correlated with any flow cytometric DNA ploidy or proliferation measurement. Tumors classified as DNA aneuploid or tetraploid, by any definition, did not differ in prognosis or correlate with stage or any pathologic parameter. Univariate Kaplan-Meier survival analysis showed prognostic significance of the following: Dukes staging, individual components of TNM stage (tumor depth, lymph node status, and metastasis), vascular invasion, histologic pattern of tumor infiltration, and peritumoral lymphocytic inflammation. DNA ploidy status and proliferation measurements were not predictive of survival for the overall group or within any particular stage. Only Dukes Stage D (metastasis), vascular invasion, and depth of invasion (T classification) were significant independent predictors of survival in multivariate Cox regression models. CONCLUSIONS: In this analysis, DNA ploidy and proliferation measurements were not predictive of survival in any stage of colorectal carcinoma. However, clinical and pathologic documentation of staging and select histopathologic observations were significant predictors of survival in univariate and multivariate analyses.

Adult↗
PubMed1997

The prognostic significance of T cell receptor beta gene rearrangements and idiotype-reactive T cells in multiple myeloma.

Clonal T cell populations with idiotype specificity are present in the peripheral blood of a proportion of patients with multiple myeloma. We have identified the presence of both T cell subpopulations with a specificity for autologous immunoglobin fragments and T cell receptor beta gene rearrangements in peripheral blood samples of patients with myeloma. T cell receptor beta gene rearrangements were detected in 38 of 119 patient samples (32%) and were more common in progressive disease (70%), than at diagnosis (25%) or in stable disease (23%). The 38 patients who had T cell receptor beta gene rearrangements detected at any time had a better overall survival (median not yet achieved) than the patients who never had rearrangements detected (median 45 months, n = 49; chi2 = 6.2, P < 0.01). All 12 patients with T cell receptor beta gene rearrangements at diagnosis are still alive whereas the median survival for 28 patients with a germline configuration at diagnosis was 40 months (chi2 = 5.8, P > 0.01). The presence of T cell receptor beta gene rearrangements even conferred a survival advantage during progressive disease (median survival 44 months vs 19 months; chi2 = 8.7, P < 0.003). Two colour flow cytometry with biotinylated autologous immunoglobulin fragments demonstrated idiotype-reactive T cells in the peripheral blood of five out of 15 patients all of whom had T cell gene rearrangements. The remaining 10 patients had neither idiotype-reactive T cells nor a detectable T cell receptor beta gene rearrangement in concurrent samples. Thus in patients with myeloma there was a good correlation between the presence of T cell receptor beta gene rearrangements and idiotype-reactive T cells. Patients with a rearranged T cell receptor beta gene had a significantly better prognosis.

Aged↗
PubMed1997

Role of G alpha q or G alpha o proteins in alpha 1-adrenoceptor subtype-mediated responses in Fischer 344 rat aorta.

Previous studies showed that alpha-adrenoceptor (AR) stimulation with norepinephrine is more potent at eliciting contraction in aortas from 1-month-old Fischer 344 rats than from older rats and that this response is mediated by alpha 1b- and alpha 1d-AR subtypes in 1-month-old rats. We examined the G proteins responsible for alpha 1-AR-mediated contractile response and inositol phosphate accumulation in the aortas of 1-month-old Fischer 344 rats. Pertussis toxin (PTX) treatment (2.5 micrograms/ml for 4 hr) of aortic rings partially inhibited phenylephrine (PHE)-stimulated contraction and inositol phosphate accumulation, suggesting the involvement of PTX-sensitive and -insensitive G proteins. Specific antisera directed against G alpha q and G alpha o but not G alpha s and G alpha i precipitated specific alpha 1-AR binding sites labeled with 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone. The number of 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone binding sites precipitated by G alpha proteins was increased by activating membrane alpha 1-ARs with PHE. Moreover, PHE stimulated the palmitoylation of G alpha q and G alpha o, and this response was blocked by the alpha 1-AR antagonist prazosin. Characterization of the alpha 1-AR subtypes that couple to G proteins indicates that although aortic alpha 1a-, alpha 1b-, and alpha 1d-ARs were associated with G alpha q, alpha 1b-AR was also linked to G alpha o. These results suggest that alpha 1-ARs mediate the contractile response in rat aorta by coupling to both Gq protein and the PTX-sensitive G(o) protein.

Animals↗
PubMed1997

Isolated angiitis of the CNS presenting as subarachnoid haemorrhage.

Isolated angiitis of the CNS (IACNS) commonly presents with recurrent ischaemic or haemorrhagic infarcts, but subarachnoid haemorrhage is rare. Three patients with IACNS and subarachnoid haemorrhage are reported. Florid granulomatous angiitis with Langhans and foreign body type giant cells was found at necropsy in a child with sudden death. In two other patients the diagnosis was made angiographically. In one patient multifocal infarcts on MRI became evident one week after subarachnoid haemorrhage despite initial treatment with prednisone. Subarachnoid haemorrhage may be the first presentation of IACNS. Characteristic radiographic findings may allow early diagnosis.

Anti-Inflammatory Agents↗
PubMed1997

Immunotoxicity of 2',3'-dideoxyinosine in female B6C3F1 mice.

2',3'-dideoxyinosine (ddI) is one of several purine analogues used for the treatment of HIV and the acquired immunodeficiency syndrome (AIDS). These nucleoside analogues are promising in their inhibition of viral reverse transcriptase and termination of DNA synthesis. However, each of these drugs has toxicity associated with its use. A previous immunotoxicological evaluation of 2',3'-dideoxyadenosine (ddA), the parent compound of ddI, showed that ddA suppresses humoral immunity. These studies were undertaken to determine the potential for immunotoxicity due to treatment with ddI. This evaluation included an assessment of innate and acquired immunity after exposure to ddI (100, 250, 500, and 1000 mg/kg/day) for 14, 28 or 180 days. There were no overt signs of toxicity related to treatment with ddI except for a decrease in body weight in the group treated with the highest dose of ddI for 180 days. Overall, 6 months of treatment with ddI showed minimal effects on specific organs with the exception of the spleen and thymus. ddI selectively targets the immune system, with assays that challenge humoral immunity being more affected than those testing cell-mediated immunity. Innate immunity was unaffected by ddI treatment. Cell-mediated immunity, as measured by proliferative response to allogeneic cells (MLR) and the T cell mitogen (Concanavalin A), was moderately suppressed. There were no ddI associated effects on NK function or macrophage function as measured by the vascular clearance rate and phagocytic uptake of the tissue macrophages. The most sensitive indicator of ddI-induced immunotoxicity is suppression of the response to the T-dependent antigen, sheep red blood cells (sRBC). The No Observable Adverse Effect Level (NOAEL) for toxicity to the immune system following 14 days of exposure to ddI is 250 mg/kg. A suppression of the humoral immune response was seen at the lowest dose tested after treatment for 28 and 180 days. Thus, the NOAEL for both of these treatment periods is below 100 mg/kg/day.

Animals↗
PubMed1997

The functional phenotype of the primitive plasma cell in patients with multiple myeloma correlates with the clinical state.

The malignant plasma cells from patients with multiple myeloma display considerable phenotypic heterogeneity. All plasma cells express high intensity CD38 (CD38++), cytoplasmic immunoglobulin and either kappa or lambda light chains. Subpopulations of mature (CD45-), immature (CD45+) and primitive (CD45++, CD19+) plasma cells can be defined but little is known about the functional differences and clinical significance of these subpopulations. Three colour flow cytometry and permeabilisation was used to determine the expression of functionally important antigens in plasma cell subpopulations. These antigens included the labelling index (LI, bromodeoxyuridine), number of nucleoside transporter per cell, p-glycoprotein (JSB-1), and oncoprotein expression (c-myc, c-fos, c-neu, bcl-2, p-ras, p53m, p-53w, and Rb). In progressive disease there was an increase in the absolute number but not the percentage of CD45++ plasma cells. There was a significant difference in the mean LI of the CD38++, CD45++ population in progressive disease compared with stable disease (9.2% vs 2.2%; z = 19.9, p < 0.001). The LI of CD45++ cells ranged up to 45% and provided a better correlation with disease status than the LI of the total cell population. Any increase in nucleoside transporters or p-glycoprotein expression was almost entirely attributable to an increase in the primitive plasma cell population. In 96% (n = 28) of samples from patients in progressive disease there was at least one abnormality in the functional phenotype of the primitive plasma cells. This is in contrast with 44% of samples from patients in stable disease (n = 58). These studies suggest that the functional phenotype of the primitive plasma cell determines the clinical phenotype of patients with myeloma.

ADP-ribosyl Cyclase↗
PubMed1997

Endovascular treatment of ruptured posterior circulation aneurysms using electrolytically detachable coils.

The authors report their experience using electrolytically detachable coils for the treatment of ruptured posterior circulation aneurysms. Twenty-six patients with 28 posterior circulation aneurysms were treated. All patients were referred for endovascular treatment by experienced vascular neurosurgeons. Patients underwent follow-up angiography immediately after treatment, 1 to 6 weeks posttreatment, and 6 months posttreatment. Six-month follow-up angiograms obtained in 19 patients with 20 aneurysms demonstrated that 18 (90%) of the 20 aneurysms were 99 to 100% occluded, one aneurysm (5%) was approximately 90% occluded, and one aneurysm (5%) was approximately 75% occluded. The patient with the aneurysm that was approximately 75% occluded needed additional treatment, consisting of parent artery balloon occlusion, and was considered a treatment failure (3.8% of patients). There was one treatment-associated mortality (3.8%) but no treatment-associated serious neurological or nonneurological morbidity in the patient group. There was no recurrent aneurysm rupture during treatment or during the mean 27-month follow-up period. Endovascular treatment of ruptured posterior circulation aneurysms with electrolytically detachable coils can be accomplished with low morbidity and mortality rates. The primary goal of treatment--preventing recurrent aneurysm--can be achieved over the short term. Endovascular coil occlusion will play an important role in the treatment of ruptured posterior circulation aneurysms, particularly if long-term efficacy in preventing recurrent aneurysm hemorrhage can be documented.

Adult↗
PubMed1997

Intra-arterial thrombolysis in acute basilar artery thromboembolism: the initial Mayo Clinic experience.

OBJECTIVE: To investigate the feasibility of intra-arterial thrombolysis in acute basilar artery thrombosis. DESIGN: We reviewed a consecutive series of patients in whom intra-arterial thrombolysis was performed during the period from 1994 to 1996. MATERIAL AND METHODS: Intra-arterial thrombolysis with urokinase was done in an attempt to recanalize the basilar artery in a series of nine patients with basilar artery thrombosis admitted to the neurologic intensive care unit. At the time of initial assessment, all nine patients had major neurologic deficits attributable to brain-stem ischemia, including two patients with locked-in syndrome. RESULTS: Recanalization of the basilar artery system was successful in seven of the nine patients (a range of 2 to 13 hours after the ictus). Failure to recanalize the basilar artery occurred in two patients, who died after progressing to coma. Complete recovery or only minimal neurologic deficits were demonstrated in five of the nine patients. Despite recanalization of the basilar artery, two patients had no major change in their neurologic function, and both ultimately had severe ataxia and were fully dependent on others. A cerebellar hemorrhage occurred in one patient but without clinical worsening. Two patients had a retroperitoneal hematoma. CONCLUSION: Intra-arterial thrombolysis with urokinase in acute basilar artery occlusion resulted in recanalization in seven of the nine patients (78%). Five of the nine patients recovered fully, including two patients who had had locked-in syndrome. In light of the devastating natural course of acute basilar artery occlusion, these initial results are encouraging and indicate that intra-arterial thrombolysis may be a useful emergency treatment, even in patients with prolonged symptoms of ischemia (up to 12 hours).

Adult↗