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Biomedical subjects

R D Brown

Publications and source records attributed to R D Brown.

At least 55 records · Page 3Linked to original sources

Contrast-enhanced magnetic resonance angiography of the cervical vessels: experience with 422 patients.

BACKGROUND AND PURPOSE: Contrast-enhanced magnetic resonance angiography (CEMRA) permits acquisition of high-spatial-resolution, venous-suppressed, 3D MR angiograms of the cervical carotid and vertebral arteries. In this study, an elliptic centric-view ordering with either MR fluoroscopic triggering or test bolus timing was used. The use of CEMRA of the cervical vessels has changed our clinical practice and is replacing conventional angiography for the evaluation of most carotid and vertebral artery diseases. METHODS: We retrospectively reviewed our experience with the use of CEMRA performed in 422 patients from January through December 1999. RESULTS: CEMRA was performed to evaluate transient ischemic attack and ischemic stroke in 239 patients, asymptomatic carotid bruit in 88 patients, and other neurological symptoms in 95 patients. Carotid endarterectomies were performed in 97 patients (103 procedures), and conventional angiography was performed in 12 of these patients. CEMRA was used to evaluate for the presence of an arterial dissection in 85 of the 239 patients with transient ischemic attack and ischemic stroke. Of this group, 32 patients had cervical arterial dissection, and pseudoaneurysm was detected in 11 of these patients. Compared with ultrasonography of the cervical vessels, CEMRA provided additional information in 43 of 422 patients and led to changes in the decision as to whether to perform carotid endarterectomy in 5 patients. CONCLUSIONS: Use of CEMRA permits noninvasive evaluation of patients suspected of having carotid or vertebral disease and avoids the potential complications of conventional angiography.

Adolescent↗

Clinical and radiographic features of dural arteriovenous fistula, a treatable cause of myelopathy.

OBJECTIVE: To assess presentation, imaging, treatment, and outcome of patients with myelopathy due to a dural arteriovenous fistula (DAVF). PATIENTS AND METHODS: This retrospective review identified 94 patients with DAVF surgically treated at our institution between June 1985 and December 1999. The mean ages of the 75 men and 19 women were 62.6 years and 63.0 years, respectively (range, 31-83 years). Magnetic resonance imaging was performed in 87 patients, computed tomography-myelography was performed in 37 patients, and spinal angiography was performed in all patients. Initial examination findings were retrospectively adjusted to a modified Aminoff-Logue myelopathy scale. RESULTS: Of the 94 patients, 47 presented with symptoms that worsened with erect posture or Valsalva maneuver. As myelopathy progressed, patients' symptoms increased, and 6 patients had paraplegia at presentation. The mean time from symptom onset to diagnosis was 23 months (range, 2-120 months). Magnetic resonance imaging confirmed the diagnosis in 86 patients; computed tomography-myelography was needed to confirm the fistula in 1 patient. Spinal angiography detected the fistula in all patients. Surgical obliteration of the DAVF was successful in 93 patients; in 1 patient surgery failed because the DAVF was not localized, but acrylic endovascular embolization was successful. No patient experienced permanent morbidity or mortality. Of the 94 patients, 93 improved postoperatively 1 or 2 levels based on a modified Aminoff-Logue scale. Older patients with severe long-term deficits had poor outcomes. CONCLUSIONS: The diagnosis of a DAVF seems to be delayed considerably because DAVF is not included in the differential diagnosis of myelopathy and because of clinicians' unfamiliarity with suggestive or revealing findings on diagnostic imaging. Neurodiagnostic imaging confirms the diagnosis, and spinal angiography localizes the fistula. Surgical intradural disconnection of the DAVF clinically reverses the pathophysiology. Additionally, surgical treatment is associated with low short-term morbidity, no permanent morbidity, and no mortality. If the diagnosis is made early and treatment initiated in such patients, they generally do well.

Adult↗

The impact of stroke on the cost and level of care in nursing homes: a retrospective population-based study.

OBJECTIVE: To estimate the impact of incident stroke on nursing home (NH) costs and level of care. SUBJECTS AND METHODS: This retrospective population-based cohort study is part of a larger study that identified all Rochester, Minn, residents with a confirmed first stroke occurring between January 1, 1988, and December 31, 1989. One Rochester resident who had not had a stroke was matched to each person with stroke. Persons with and without stroke were followed up in provider-linked medical records and NH files from baseline (i.e., date of stroke) through December 31, 1994, for evidence of NH use. This study characterized the NH activity of those individuals with any NH activity after baseline (58 persons with major stroke, 36 persons with minor stroke, and 63 persons without stroke) as to NH case mix at first assessment, number of NH days, and per diem Medicaid reimbursement. RESULTS: Characteristics at first NH assessment after baseline revealed that NH residents with major stroke were younger and more disabled and required more services than residents without stroke. Over the full period of follow-up, the mean number of NH days was similar for NH residents with major stroke and those without stroke, yet per diem Medicaid reimbursement was 11% higher for residents with major stroke compared with residents without stroke. Nursing home residents with minor stroke appeared similar to those without stroke with respect to time to admission, characteristics at first assessment, number of NH days, and per diem Medicaid reimbursement. CONCLUSION: Lower incidence and severity of stroke may contribute to lower care needs and per diem cost, but no fewer NH days.

Activities of Daily Living↗

Carbon tetrachloride is immunosuppressive and decreases host resistance to Listeria monocytogenes and Streptococcus pneumoniae in female B6C3F1 mice.

Carbon tetrachloride (CCl(4)) is an environmental contaminant that has been detected in ambient air, seawater, surface-water and snow. The immunotoxic potential of CCl(4) was evaluated in female B6C3F1 mice. The animals were administered with CCl(4) daily for 14 days at doses of 50, 100, 500 or 1000 mg/kg body weight by gavage with corn oil as a vehicle. Exposure to CCl(4) resulted in an increase of liver weight but not the body weight and the weights of brain, spleen, lungs, thymus and kidneys. Exposure to CCl(4) produced minimal effect on differential hematological parameters; however, it produced a significant increase in serum glutamic-pyruvic transaminase (SGPT) levels in all dose groups while other serum chemistries showed sporadic increases, primarily at the dose level of 1000 mg/kg. Exposure to CCl(4) produced a decreased humoral immune response; the IgM antibody forming cell (AFC) response to sheep red blood cells (sRBC) was suppressed with the maximal decrease (45%) observed at the dose level of 1000 mg/kg. The IgM serum titer to sRBC was also reduced with a maximal decrease (54%) observed at the dose level of 500 mg/kg. Although exposure to CCl(4) had no effects on the mixed leukocyte response (MLR), cytotoxic T lymphocyte activity and natural killer (NK) cell activity, a decrease in both the absolute number and the percentage of CD4(+)CD8(-) at the dose level of 500 mg/kg was observed. The functional activity of the mononuclear phagocyte system was compromised as reflected by a decrease in the vascular clearance of (51)Cr-sRBC and a decrease in the uptake of (51)Cr-sRBC by the liver. Finally, in the two host resistance models evaluated, exposure to CCl(4) decreased host resistance to both Streptococcus pneumoniae and Listeria monocytogenes with greater susceptibility to the latter. Overall, these studies demonstrate that CCl(4) was immunosuppressive in female B6C3F1 mice.

Alanine Transaminase↗

B7-2-positive myeloma: incidence, clinical characteristics, prognostic significance, and implications for tumor immunotherapy.

Deficiencies in B7:CD28 costimulation are considered to be one of the major causes of the failure to generate a tumor-specific immune response. Up-regulating the expression of the B7 molecules on malignant B cells has been shown to stimulate cytotoxic T cells. Plasma cells from patients with myeloma express a tumor-specific idiotype but lack CD80 (B7-1) and have a variable expression of CD86 (B7-2). This study has identified the incidence and clinical significance of high CD86 expression on plasma cells at diagnosis and studied the ability of trimeric human CD40 ligand (huCD40LT) to up-regulate the expression of the B7 family on malignant plasma cells. CD86 expression on plasma cells was increased in 54% of the patients studied at diagnosis (n = 35) and was associated with a significantly shorter survival (median, 28 versus 57 months; chi(2) = 4.6; P =.03) and a higher tumor load (patients with more than 50% bone marrow plasma cells, 47% versus 6%; chi(2) = 7.2; P =.005). CD86 expression was highest on immature and primitive plasma cells (CD38(++), CD45(+)) of both patients and controls and was associated with a CD40(+), CD20(+), CD19(-), CD138(+) phenotype. The shortened survival was associated with high CD86 only on mature (CD38(++), CD45(-)) plasma cells (chi(2) = 7.6; P =.006). There was no significant correlation between high CD86 and other known prognostic markers, including serum beta(2)-microglobulin, serum thymidine kinase, and labeling index. The addition of huCD40LT to short-term cultures up-regulated both CD80 and CD86 expression on B cells (CD19(+)) and CD80 on plasma cells (CD38(++)), but did not up-regulate CD86 expression on plasma cells. Thus, B7-2-positive myeloma consists of a subgroup of patients with a relatively poor prognosis, and CD40LT may be useful in immunotherapy protocols because it up-regulates CD80 expression on malignant plasma cells without inducing B7-2-positive myeloma. (Blood. 2000;96:1274-1279)

Adult↗

Thalidomide stimulates splenic IgM antibody response and cytotoxic T lymphocyte activity and alters leukocyte subpopulation numbers in female B6C3F1 mice.

Thalidomide has been shown to have antiinflammatory and, more recently, immunomodulating properties, which are beneficial for the treatment of an ever-increasing list of immune related diseases. Although considerable knowledge regarding thalidomide s antiinflammatory properties has been acquired, relatively little is known about its immunomodulating properties in vivo. In this paper, a panel of immune assays was used to evaluate immunomodulation in female B6C3F1 mice treated intraperitoneally for 28 days with thalidomide (30, 100, or 150 mg/kg/day). Spleen antibody forming cell response was significantly enhanced by 37% in mice treated with 150 mg/kg/day, despite an 8% decrease in the percentage of Ig+ B cells. A significant stimulatory trend was observed for the cytotoxic T cell response across thalidomide treatment groups. An evaluation of the spleen leukocyte subpopulations revealed a 23% increase in the absolute number of CD8+ T cells in the 150 mg/kg treatment group and a 9 and 11% decrease in the absolute number of NK cells in both the 100 and 150 mg/kg thalidomide treatment groups, respectively. These findings demonstrate that, in addition to modulating spleen leukocyte numbers, thalidomide also stimulates murine humoral and cellular immune responses in vivo.

Animals↗

Cerebral infarction and transient ischemic attacks. Efficient evaluation is essential to beneficial intervention.

Rapid but precise evaluation of patients presenting with cerebral infarction is essential to determine immediate intervention. Initial assessment should include history taking, physical examination, routine laboratory testing, electrocardiography, chest radiology, and noncontrast head CT. Localizing the event to the appropriate arterial circulation (anterior versus posterior) and determining topography (subcortical versus cortical) guide sequential testing to ascertain the mechanism of cerebral infarction. Diagnostic testing focuses on selectively identifying potential cardiac, large-vessel, small-vessel, or hematologic causes. Although diagnostic tools are evolving, 15% of cerebral infarctions still have an unknown cause or multiple potential sources.

Cerebral Infarction↗

Hypermethylation of E-cadherin in leukemia.

E-cadherin gene is often termed a "metastasis suppressor" gene because the E-cadherin protein can suppress tumor cell invasion and metastasis. Inactivation of the E-cadherin gene occurs in undifferentiated solid tumors by both genetic and epigenetic mechanisms; however, the role of E-cadherin in hematologic malignancies is only now being recognized. E-cadherin expression is essential for erythroblast and normoblast maturation, yet expression is reduced or absent in leukemic blast cells. This study examined the messenger RNA (mRNA) and protein expression of the E-cadherin gene in bone marrow and blood samples from normal donors and patients with leukemia. We found that all normal donor samples expressed E-cadherin mRNA, whereas both samples of acute myelogenous leukemia and chronic lymphocytic leukemia had a significant reduction or absence of expression. However, normal blast counterparts expressed only a low level of E-cadherin surface protein. Sodium bisulphite genomic sequencing was used to fully characterize the methylation patterns of the CpG island associated with the E-cadherin gene promoter in those samples with matched DNA. All of the normal control samples were essentially unmethylated; however, 14 of 18 (78%) of the leukemia samples had abnormal hypermethylation of the E-cadherin CpG island. In fact both alleles of the E-cadherin gene were often hypermethylated. We conclude the E-cadherin gene is a common target for hypermethylation in hematologic malignancies.

Base Sequence↗

Endoscopic transpapillary drainage of pancreatic abscess: technique and results.

BACKGROUND: Pancreatic abscess is one of the serious complications of acute pancreatitis. Traditionally, pancreatic abscess has been treated by operative drainage. Based on experience with endoscopic transpapillary drainage of pseudocysts, a similar technique was used in patients with pancreatic abscess. METHOD: Patients were evaluated by endoscopic retrograde cholangiopancreatography. In those with pancreatic abscess communicating with the main pancreatic duct, pancreatic sphincterotomy, saline irrigation of the abscess cavity, and catheter dilation followed by 10F pancreatic stent placement were done. Instillation of gentamicin and nasopancreatic catheter drainage were used in difficult cases. RESULTS: Of 22 patients with pancreatic abscess, 11 underwent endoscopic transpapillary drainage with technical success in 10 patients (90%); 8 patients (74%) had resolution of pancreatic abscess, clinically and radiographically. Intracavitary instillation of gentamicin and nasopancreatic catheter drainage were used in 2 patients. Two patients in whom endoscopic transpapillary drainage failed underwent operative drainage with a favorable outcome, and the one patient in whom endoscopic treatment was technically unsuccessful underwent successful percutaneous drainage. One patient had mild pancreatitis. CONCLUSION: Endoscopic transpapillary drainage is an effective nonoperative therapy for selected cases of pancreatic abscess and is associated with minimal morbidity and no mortality.

Abdominal Abscess↗

T-cell expansions in patients with multiple myeloma have a phenotype of cytotoxic T cells.

The presence of T-cell clones in peripheral blood has been previously shown to be associated with a survival advantage in patients with multiple myeloma and suggests that the expanded T-cell populations may be involved in an anti-tumour response. We studied the T-cell receptor (TCR) repertoire of 38 patients with myeloma to identify and characterize the expanded T-cell populations by flow cytometry. T-cell expansions were found in 79% of the patients. The expansions occurred randomly among the 21 variable regions of the TCR beta chain (Vbeta) studied, representing 62% of the V-beta repertoire, and were stable during an 18-month follow-up. The phenotype of the expanded V-beta populations was predominantly CD8+, CD57+, CD28- and perforin+, which differed significantly from the other non-expanded Vbeta populations. The expression of the apoptosis markers Fas (CD95) and bcl-2 were similar between the expanded and non-expanded Vbeta populations. In conclusion, expanded T-cell populations were frequent in patients with myeloma, they remained unchanged during follow-up and had phenotypic characteristics of cytotoxic T cells. These data add further support to the concept that the T-cell expansions may have an immunoregulatory role in myeloma.

Aged↗

Glycidol modulation of the immune responses in female B6C3F1 mice.

The immunotoxic potential of glycidol was evaluated in female B6C3F1 mice using a battery of functional assays and three host resistance models. Glycidol was administered to the animals by oral gavage as a solution in sterile distilled water daily for 14 days at doses of 25, 125 and 250 mg/kg. In tier I, we observed that glycidol exposure produced a dose-related decrease in splenocyte IgM antibody-forming cell response to sheep red blood cells (sRBC); the spleen natural killer (NK) cell activity was also decreased. A decrease in B cell proliferative responses to anti-IgM F(ab')2 and/or interleukin-4 (IL-4) was observed while the splenocyte proliferative responses to T cell mitogen ConA and B cell mitogen LPS were not affected. The splenocyte proliferative response to allogeneic cells as evaluated in the mixed leukocyte reaction (MLR) to DBA/2 spleen cells was not affected. In tier II, we found that exposure to glycidol decreased the number and percentage of B cells and the absolute number of CD4+ T cells in the spleen while the number of total T cells, CD8+ T cells and CD4+CD8+ T cells was not affected. The cytotoxic T lymphocyte (CTL) response to mitomycin C-treated P815 mastocytoma was not affected; the cytotoxic activity of peritoneal macrophages was not suppressed. Moreover, the host resistance to Listeria monocytogenes was not affected although a slight increase in host resistance to Streptococcus pneumoniae was observed. However, exposure to glycidol decreased host resistance to the B16F10 melanoma tumor model with the maximal tumor formation in lung observed in the high dose group. Overall, these dada support the finding that glycidol is an immunosuppressive agent in female B6C3F1 mice.

Animals↗

Ischemic stroke subtypes : a population-based study of functional outcome, survival, and recurrence.

BACKGROUND AND PURPOSE: There is scant population-based information on functional outcome, survival, and recurrence for ischemic stroke subtypes. METHODS: We identified all residents of Rochester, Minnesota, with a first ischemic stroke from 1985 through 1989 using the resources of the Rochester Epidemiology Project medical records linkage system. After reviewing medical records and imaging studies, we assigned patients to 4 major ischemic stroke categories based on National Institute of Neurological Diseases and Stroke Data Bank criteria: large-vessel cervical or intracranial atherosclerosis with stenosis (ATH, n=74), cardioembolic (CE, n=132), lacunar (LAC, n=72), and infarct of uncertain cause (IUC, n=164). We used the Rankin disability score to assess functional outcome and the Kaplan-Meier product-limit method and Cox proportional hazards regression analysis with bootstrap validation to estimate rates and identify predictors of survival and recurrent stroke among these patients. RESULTS: Rankin disabilities were different across stroke subtypes at the time of stroke and 3 months and 1 year later (P=0.001). LAC was associated with milder deficits compared with other subtypes. Mean follow-up among the 442 patients in the cohort was 3.2 years. Estimated rates of recurrent stroke at 30 days were significantly different (P<0.001): ATH, 18.5% (95% CI 9.4% to 27.5%); CE, 5.3% (95% CI 1.2% to 9.6%); LAC, 1.4% (95% CI 0.0% to 4.1%); and IUC, 3. 3% (95% CI 0.4% to 6.2%). After adjusting for age, sex, and stroke severity, infarct subtype was an independent determinant of recurrent stroke within 30 days (P=0.0006; eg, risk ratio for ATH compared with CE=3.3, 95% CI 1.2 to 9.3) but not long term (P=0.07). Four of 25 recurrent strokes within 30 days were procedure-related, each in patients with ATH. Five-year death rates were significantly different (P<0.001): ATH, 32.2% (95% CI 21.1% to 43.2%); CE, 80.4% (95% CI 73.1% to 87.6%); LAC, 35.1% (95% CI 23.6% to 46.0%); and IUC, 48.6% (95% CI 40.5% to 56.7%). With adjustment for age, sex, cardiac comorbidity, and stroke severity, the subtype of ischemic stroke was an independent determinant of long-term (P=0.018; eg, risk ratio for ATH compared with cardioembolic=0.47, 95% CI 0.29 to 0.77) but not 30-day survival (P=0.2). CONCLUSIONS: Early recurrence rates for ischemic stroke caused by ATH are higher than those for other subtypes and higher than previous non-population-based studies have reported. Some of the increased risk of early recurrence among patients with ATH may be iatrogenic. Patients with LAC have better poststroke functional status than those with other subtypes. Survival is poorest among those with ischemic stroke with a cardiac source of embolism.

Adult↗

Verifying the stroke-free phenotype by structured telephone interview.

BACKGROUND AND PURPOSE: Case-control, cohort, and twin studies support a genetic contribution to ischemic stroke risk. Sibling pair linkage methods require identification of concordant or discordant siblings or both. We designed and tested a structured telephone interview to verify the stroke-free phenotype. METHODS: A coordinator unaware of medical record data used an 8-item questionnaire to conduct a structured telephone interview of 70 outpatients aged >60 years. The questionnaire inquired about the sudden onset of deficits in strength, sensation, vision, and language. A subject was defined as stroke free by interview if responses to all items on the questionnaire were negative. Results of the telephone interview were compared with data obtained from a systematic medical record review (benchmark). RESULTS: Interview time was 5 minutes or less for all subjects. All subjects who began the interview completed it. Records were reviewed in all subjects. Medical record review detected ischemic stroke or transient ischemic attack (TIA), or both, in 5 patients (7%). There were no significant differences in sex distribution or risk factor rates in patients who were designated stroke free or not stroke free by interview. Having 1 or more positive items on the questionnaire was significantly associated with finding stroke (P<0.001), TIA (P<0.001), or either stroke or TIA (P<0.001), on medical record review. The telephone interview had a sensitivity of 1.0 (95% CI 0.48 to 1.0), specificity of 0.86 (95% CI 0.75 to 0.93), positive predictive value of 0.36 (95% CI 0.13 to 0.65), and negative predictive value of 1.0 (95% CI 0.94 to 1.0). CONCLUSIONS: Our instrument can identify the stroke-free individual with a high degree of confidence in a very efficient manner. It may be particularly suited for centralized verification of stroke discordancy in multicentered sib-pair genetic studies.

Aged↗

Acetaminophen controlled-release sprinkles versus acetaminophen immediate-release elixir in febrile children.

Current acetaminophen (APAP) formulations approved for antipyretic use in children require up to five doses/day, which compromise compliance and risk breakthrough fever over 4 hours after dosing. A total of 112 evaluable febrile children received oral APAP-equivalent doses of either one dose of APAP controlled release (CR) as sprinkles on applesauce or one dose q 4 hours x 2 of APAP immediate-release (IR) elixir in an 8-hour, double-blind, double-dummy, randomized, multicenter study. Prior or concurrent antibiotic use did not significantly affect either the magnitude or the pattern of temperature reduction during the 8-hour observation period. Significantly greater aural temperature reductions were found with APAP-CR than with APAP-IR at 4 and 5 hours. However, the 8-hour AUCs of temperature reduction were not significantly different between treatments. Pharmacokinetic/pharmacodynamic modeling of APAP was performed in 8 patients with values in both treatments similar to previous results, except for expected differences in AUC0-infinity. Similar 8-hour temperature reduction for APAP-CR (one dose) and APAP-IR (two doses) demonstrates the efficacy of APAP-CR as an antipyretic in children 2 to 11 years of age. A decrease in the number of APAP daily doses and the prolonged antipyretic effect of APAP-CR may assist those who care for febrile children at home.

Acetaminophen↗

Redefined duplex ultrasonographic criteria for diagnosis of carotid artery stenosis.

OBJECTIVE: To evaluate duplex ultrasonographic criteria for the determination of 50% or more and 70% or more stenosis of the diameter of the internal carotid artery based on conventional angiography in order to align ultrasonographic diagnostic categories with current clinical management schemes. PATIENTS AND METHODS: Between January 1, 1995, and June 30, 1999, 915 patients underwent both carotid duplex ultrasonography and cerebral angiography within 30 days at Mayo Clinic, Rochester, Minn. Of these patients, 294 were excluded from this study because of occlusion of one or both of the internal carotid arteries or atypical flow characteristics. In the remaining 621 patients (61 % male, 39% female; mean age, 67.7 years [range, 14-88 years]), 1218 vessels were available for correlation. Several Doppler ultrasonographic velocity variables were compared with the angiographic findings by use of receiver operating characteristic curve analysis. The primary end point was verification of optimal ultrasonographic criteria to diagnose 70% or more internal carotid artery stenosis. The secondary end point was establishment of threshold values to detect stenosis of 50% or more. RESULTS: At angiography, 382 patients had internal carotid arteries with 70% or more stenosis. Peak systolic and end diastolic velocities of the internal carotid artery and internal carotid artery:common carotid artery peak systolic velocity ratios were measured. For an internal carotid artery stenosis of 70% or more, a peak systolic velocity of 230 cm/s or more resulted in a sensitivity of 86.4%, a specificity of 90.1%, a positive predictive value of 82.7%, a negative predictive value of 92.3%, and an accuracy of 88.8%. An end diastolic velocity of 70 cm/s or more and an internal carotid artery:common carotid artery ratio of 3.2 or more yielded similar values. For an internal carotid artery stenosis of 50% or more, a peak systolic velocity of 130 cm/s or more resulted in a sensitivity of 92.1 %, a specificity of 89.5%, a positive predictive value of 90.3%, a negative predictive value of 91.3%, and an overall accuracy of 90.8%. An internal carotid artery:common carotid artery ratio of 1.6 or more yielded similar values. CONCLUSION: In our ultrasonography laboratory, a carotid artery stenosis of 70% or more (for which carotid endarterectomy is typically recommended in symptomatic patients) is diagnosed reliably with the following duplex ultrasonographic criteria: a peak systolic velocity of 230 cm/s or more, an end diastolic velocity of 70 cm/s or more, or an internal carotid artery:common carotid artery ratio of 3.2 or more.

Adolescent↗