Biomedical subjects

D L Brown

Publications and source records attributed to D L Brown.

At least 19 recordsLinked to original sources

PubMed2007

Mesenchymal hamartoma of the liver in a late-term equine fetus.

Mesenchymal hamartoma of the liver is a rare congenital disorder of biliary tract development. During the necropsy of a late-term equine fetus, a markedly enlarged liver of more than two times normal weight was found. Light microscopic review revealed that the normal hepatic parenchyma had been obliterated, replaced, and expanded by abnormal bile ducts surrounded by abundant, myxoid stroma. The lesion was diagnosed as a mesenchymal hamartoma. Small portions of the liver had bridging septa of fibrosis and proliferations of small-caliber abnormal bile ducts, resembling another congenital biliary abnormality termed congenital hepatic fibrosis.

Animals↗

PubMed2006

Projected costs of ischemic stroke in the United States.

BACKGROUND: There are barriers to acute stroke care in minority groups as well as a higher incidence of ischemic stroke when compared with non-Hispanic whites. OBJECTIVE: To estimate the future economic burden of stroke in non-Hispanic whites, Hispanics, and African Americans in the United States from 2005 to 2050. METHODS: We used U.S. Census estimates of the race-ethnic group populations age 45 years and older. We obtained stroke epidemiology and service utilization data from the Northern Manhattan Stroke Study and the Brain Attack Surveillance in Corpus Christi project and other published data. We estimated costs directly from Medicare reimbursement or from studies that used Medicare reimbursement. Direct and indirect costs considered included ambulance services, initial hospitalization, rehabilitation, nursing home costs, outpatient clinic visits, drugs, informal caregiving, and potential lost earnings. RESULTS: The total cost of stroke from 2005 to 2050, in 2005 dollars, is projected to be 1.52 trillion dollars for non-Hispanic whites, 313 billion dollars for Hispanics, and 379 billion dollars for African Americans. The per capita cost of stroke estimates are highest in African Americans (25,782 dollars), followed by Hispanics (17,201 dollars), and non-Hispanic whites (15,597 dollars). Loss of earnings is expected to be the highest cost contributor in each race-ethnic group. CONCLUSIONS: The economic burden of stroke in African Americans and Hispanics will be enormous over the next several decades. Further efforts to improve stroke prevention and treatment in these high stroke risk groups are necessary.

Black or African American↗

PubMed2006

Vascularized tissue-engineered chambers promote survival and function of transplanted islets and improve glycemic control.

We have developed a chamber model of islet engraftment that optimizes islet survival by rapidly restoring islet-extracellular matrix relationships and vascularization. Our aim was to assess the ability of syngeneic adult islets seeded into blood vessel-containing chambers to correct streptozotocin-induced diabetes in mice. Approximately 350 syngeneic islets suspended in Matrigel extracellular matrix were inserted into chambers based on either the splenic or groin (epigastric) vascular beds, or, in the standard approach, injected under the renal capsule. Blood glucose was monitored weekly for 7 weeks, and an intraperitoneal glucose tolerance test performed at 6 weeks in the presence of the islet grafts. Relative to untreated diabetic animals, glycemic control significantly improved in all islet transplant groups, strongly correlating with islet counts in the graft (P<0.01), and with best results in the splenic chamber group. Glycemic control deteriorated after chambers were surgically removed at week 8. Immunohistochemistry revealed islets with abundant insulin content in grafts from all groups, but with significantly more islets in splenic chamber grafts than the other treatment groups (P<0.05). It is concluded that hyperglycemia in experimental type 1 diabetes can be effectively treated by islets seeded into a vascularized chamber functioning as a "pancreatic organoid."

Animals↗

PubMed2006

Differences in intracerebral hemorrhage between Mexican Americans and non-Hispanic whites.

BACKGROUND: Mexican Americans (MAs) have higher incidence rates of intracerebral hemorrhage (ICH) than non-Hispanic whites (NHWs). The authors present clinical and imaging characteristics of ICH in MAs and NHWs in a population-based study. METHODS: This work is part of the Brain Attack Surveillance in Corpus Christi (BASIC) project. Cases of nontraumatic ICH were identified from 2000 to 2003. Multivariable logistic regression was used to assess the independent associations between ethnicity and ICH location (lobar vs nonlobar) and volume (> or = 30 vs < 30 mL), adjusting for demographics and baseline clinical characteristics. Logistic regression was also used to determine the association between ethnicity and in-hospital mortality, adjusting for confounders. RESULTS: A total of 149 MAs and 111 NHWs with ICH were identified. MAs were younger (70 vs 77, p < 0.001), more often male (55% vs 42%, p = 0.04), had a lower prevalence of atrial fibrillation (2.0% vs 13%, p < 0.001), and a higher prevalence of diabetes (39% vs 19%, p < 0.001). MA ethnicity was independently associated with nonlobar hemorrhage (OR 2.08, 95% CI: 1.15, 3.70). MAs had over two times the odds of having small (< 30 mL) hemorrhages compared with NHWs (OR = 2.41, 95% CI: 1.31, 4.46). NHWs had higher in-hospital mortality, though this association was no longer significant after adjustment for ICH volume, location, age, and sex. CONCLUSIONS: There are significant differences in the characteristics of ICH in MAs and NHWs, with MA patients more likely to have smaller, nonlobar hemorrhages. These differences may be used to examine the underlying pathophysiology of ICH.

Age of Onset↗

PubMed2006

Presentation of intracerebral haemorrhage in a community.

BACKGROUND: Studies on intracerebral haemorrhage (ICH) from tertiary care centres may not be an accurate representation of the true spectrum of disease presentation. OBJECTIVE: To describe the clinical and imaging presentation of ICH in a community devoid of the referral bias of an academic medical centre; and to investigate factors associated with lower Glasgow coma scale (GCS) score at presentation, as GCS is crucial to early clinical decision making. METHODS: The study formed part of the BASIC project (Brain Attack Surveillance in Corpus Christi), a population based stroke surveillance study in a bi-ethnic Texas community. Cases of first non-traumatic ICH were identified from years 2000 to 2003, using active and passive surveillance. Clinical data were collected from medical records by trained abstractors, and all computed tomography (CT) scans were reviewed by a study physician. Multivariable linear regression was used to identify clinical and CT predictors of a lower GCS score. RESULTS: 260 cases of non-traumatic ICH were identified. Median ICH volume was 11 ml (interquartile range 3 to 36) with hydrocephalus noted in 45%. Median initial GCS score was 12.5 (7 to 15). Hydrocephalus score (p = 0.0014), ambient cistern effacement (p = 0.0002), ICH volume (p = 0.014), and female sex (p = 0.024) were independently associated with lower GCS score at presentation, adjusting for other variables. CONCLUSIONS: ICH has a wide range of severity at presentation. Hydrocephalus is a potentially reversible cause of a lower GCS score. Since early withdrawal of care decisions are often based on initial GCS, recognition of the important influence of hydrocephalus on GCS is warranted before withdrawal of care decisions are made.

Aged↗

PubMed2005

Predictors of noninvasive ventilation tolerance in patients with amyotrophic lateral sclerosis.

Noninvasive ventilation (NIV) appears to improve survival and quality of life in patients with amyotrophic lateral sclerosis (ALS), but little is known about predictors of NIV tolerance. NIV use was assessed and clinical predictors of tolerance were investigated, using predictive modeling, in ALS patients diagnosed and followed in our clinic until death over a 4-year time period. Patients were prescribed NIV based on current practice parameters when respiratory symptoms were present or forced vital capacity was less than 50%. We prescribed NIV in 52% (72) of patients. For those prescribed NIV, information regarding tolerance was available for 50 patients, with 72% (36) tolerant to its use. Tolerance was six times more likely in limb-onset than bulbar-onset ALS patients, with a trend toward reduced tolerance in those with lower forced vital capacity at NIV initiation. Age, gender, and duration of disease were not predictors of NIV tolerance. We conclude that a majority of ALS patients who are prescribed NIV can successfully become tolerant to its use.

Aged↗

PubMed2004

Emergency department evaluation of ischemic stroke and TIA: the BASIC Project.

OBJECTIVE: To identify demographic and clinical variables of emergency department (ED) practices in a community-based acute stroke study. METHODS: By both active and passive surveillance, the authors identified cerebrovascular disease cases in Nueces County, TX, as part of the Brain Attack Surveillance in Corpus Christi (BASIC) Project, a population-based stroke surveillance study, between January 1, 2000, and December 31, 2002. With use of multivariable logistic regression, variables independently associated with three separate outcomes were sought: hospital admission, brain imaging in the ED, and neurologist consultation in the ED. Prespecified variables included age, sex, ethnicity, insurance status, NIH Stroke Scale score, type of stroke (ischemic stroke or TIA), vascular risk factors, and symptom presentation variables. Percentage use of recombinant tissue plasminogen activator (rt-PA) was calculated. RESULTS: A total of 941 Mexican Americans (MAs) and 855 non-Hispanic whites (NHWs) were seen for ischemic stroke (66%) or TIA (34%). Only 8% of patients received an in-person neurology consultation in the ED, and 12% did not receive any head imaging. TIA was negatively associated with neurology consultations compared with completed stroke (odds ratio [OR] 0.35 [95% CI 0.21 to 0.57]). TIA (OR 0.14 [0.10 to 0.19]) and sensory symptoms (OR 0.59 [0.44 to 0.81]) were also negatively associated with hospital admission. MAs (OR 0.58 [0.35 to 0.98]) were less likely to have neurology consultations in the ED than NHWs. Only 1.7% of patients were treated with rt-PA. CONCLUSIONS: Neurologists are seldom involved with acute cerebrovascular care in the emergency department (ED), especially in patients with TIA. Greater neurologist involvement may improve acute stroke diagnosis and treatment efforts in the ED.

Aged↗

PubMed2004

Human immunodeficiency and hepatitis virus infections and their associated conditions and treatments among people with haemophilia.

Treatment with contaminated plasma products before 1990 resulted in extraordinary prevalence rates of human immunodeficiency virus (HIV) and hepatitis B and C viruses (HBV, HCV). In the Second Multicentre Haemophilia Cohort Study (MHCS-II) during 2001-03, 30% of HCV-seropositive survivors had HIV and 4.6% were HBV carriers. Highly active antiretroviral therapy (HAART) radically altered the consequences of HIV/HCV coinfection. Whereas opportunistic infections predominated previously, current major complications are liver failure and bleeding (exacerbated by decreased clotting factor synthesis, hypersplenic thrombocytopenia, and oesophageal varices). Most HIV-positives in MHCS-II were HIV RNA-negative and had > 200 CD4(+) cells microL(-1), but only 59% were on HAART. With HIV, especially after 41 years of age, liver disease was apparent (jaundice in 5%, ascites 7%, hepatomegaly 9%, splenomegaly 19%). HAART increases survival but may contribute to various comorbidities. Without HIV, sustained HCV clearance is obtained in > 50% with combined pegylated interferons plus ribavirin, but data in haemophilic populations, especially with HIV, are limited. In MHCS-II, HCV RNA negativity was 41% following standard interferon plus ribavirin; among interferon-naive participants (implying spontaneous HCV clearance), HCV RNA negativity was 12% with and 25% without HIV. Without HIV, spontaneous HCV clearance was much more likely with early age at infection and particularly with recent birth (late 1970s or early 1980s) but not with bleeding propensity or its treatment. Most (72%) participants had received no anti-HCV therapy. Hepatic and haematological conditions are likely to increase during the coming years unless most adult haemophiliacs are successfully treated for HIV, HCV or both.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Incubation of European yew (Taxus baccata) with white-tailed deer (Odocoileus virginianus) rumen fluid reduces taxine A concentrations.

Yew ( Taxus baccata) foliage was co-incubated with rumen fluid (RF) taken from fistulated cattle (Bos taurus), anesthetized white-tailed deer (Odocoileus virginianus) and O. virginianus killed by bow hunters. The first trial with live deer resulted in statistically significant 59% reduction of taxine A by deer RF and no reduction by cattle RF. The second intubation trial, in which half the samples were stopped after 12 h, resulted in slightly less taxine A reduction by deer (46%) and 12% reduction by cattle RF. RF obtained by hunters eQuipped with thermos bottles and trained to collect RF immediatey upon field dressing their deer caused the most (88-96%) taxine A destruction: cattle RF reduced 68-88% the toxin. Obtaining RF from freshly killed deer was less expensive and more consistently successful than taking RF by intubation of anesthetized deer. The greater ability of white-tailed deer RF to detoxify yew taxines may not entirely explain the advantage white-tailed deer have over cattle to surviveyew ingestions without toxic effects.

Alkaloids↗

PubMed2003

A common mutation, Arg457-->Gln, links prothrombin deficiencies in the Puerto Rican population.

Five unrelated families with Puerto Rican ancestry were identified as having at least one member with bleeding due to a prothrombin deficiency. Genetic prothrombin deficiencies are extremely rare, but at the University of Puerto Rico Hemophilia Center, prothrombin deficiency is the third most common congenital coagulation factor deficiency. Because Puerto Rico is relatively isolated, there was a reasonable expectation of a founder effect. Prothrombin genes from probands and their parents were directly sequenced from PCR amplified exons using forward and reverse primers. Four novel prothrombin mutations were identified. The first, a G-->A substitution at DNA position 10150 predicting an Arg457-->Gln (R457Q) replacement, is common to all five families. In two of the families, the proband children are homozygous for R457Q. In the other three families, the probands are compound heterozygotes for R457Q and one of the other three mutations, which include another point mutation (gamma16Q), a deletion and a splice junction mutation. The two point mutations have been designated Puerto Rico I and Puerto Rico II. The crystal structure of alpha-thrombin predicts that the R457Q mutation removes a salt bridge that links the A- and B-chains of thrombin. The primary effect of this defect appears to be destabilization of the circulating prothrombin, creating a moderate hypoprothrombinemia. However, prothrombin antigen/activity ratios indicate a dysprothrombinemia as well, most likely due to the inability of R457Q prothrombin to activate fully to thrombin.

Adolescent↗

PubMed2003

Deaths associated with platelet glycoprotein IIb/IIIa inhibitor treatment.

BACKGROUND: The glycoprotein (GP) IIb/IIIa inhibitors are potent antagonists of platelet aggregation that are approved to prevent thrombotic complications of percutaneous coronary intervention and for medical treatment of patients with acute coronary ischaemic syndromes. From safety data obtained from clinical trials, these agents appear to be associated with a definite but well tolerated increase in non-fatal bleeding complications. However, the bleeding risk of patients enrolled in clinical trials may not be representative of the population actually being treated with these agents. OBJECTIVE: To conduct a review of the adverse events related to GP IIb/IIIa inhibitors reported to the Food and Drug Administration (FDA). METHODS: 450 reports of death related to treatment with GP IIb/IIIa inhibitors were submitted to the FDA between 1 November 1997 and 31 December 2000. These were reviewed and a standard rating system for assessing causation was applied to each event. RESULTS: Of the 450 deaths, 44% were considered to be definitely or probably related to the use of GP IIb/IIIa inhibitors. The mean age of patients who died was 69 years and 47% of deaths occurred in women. All of the deaths deemed to be definitely or probably related to GP IIb/IIIa inhibitor treatment were associated with excessive bleeding. The central nervous system was the most common site of fatal bleeding. CONCLUSIONS: Treatment with GP IIb/IIIa inhibitors may result in fatal bleeding complications in some patients. These findings suggest that patients treated in normal clinical practice may be at greater risk than those treated in clinical trials. Judicious use of these agents is therefore appropriate.

Abciximab↗

PubMed2002

Dose responses for adaption to low doses of (60)Co gamma rays and (3)H beta particles in normal human fibroblasts.

The dose response for adaption to radiation at low doses was compared in normal human fibroblasts (AG1522) exposed to either (60)Co gamma rays or (3)H beta particles. Cells were grown in culture to confluence and exposed at either 37 degrees C or 0 degrees C to (3)H beta-particle or (60)Co gamma-ray adapting doses ranging from 0.1 mGy to 500 mGy. These cells, and unexposed control cells, were allowed to adapt during a fixed 3-h, 37 degrees C incubation prior to a 4-Gy challenge dose of (60)Co gamma rays. Adaption was assessed by measuring micronucleus frequency in cytokinesis-blocked, binucleate cells. No adaption was detected in cells exposed to (60)Co gamma radiation at 37 degrees C after a dose of 0.1 mGy given at a low dose rate or to 500 mGy given at a high dose rate. However, low-dose-rate exposure (1-3 mGy/min) to any dose between 1 and 500 mGy from either radiation, delivered at either temperature, caused cells to adapt and reduced the micronucleus frequency that resulted from the subsequent 4-Gy exposure. Within this dose range, the magnitude of the reduction was the same, regardless of the dose or radiation type. These results demonstrate that doses as low as (on average) about one track per cell (1 mGy) produce the same maximum adaptive response as do doses that deposit many tracks per cell, and that the two radiations were not different in this regard. Exposure at a temperature where metabolic processes, including DNA repair, were inactive (0 degrees C) did not alter the result, indicating that the adaptive response is not sensitive to changes in the accumulation of DNA damage within this range. The results also show that the RBE for low doses of tritium beta-particle radiation is 1, using adaption as the end point.

Acclimatization↗

PubMed2001

Sex-based differences in early mortality of patients undergoing primary angioplasty for first acute myocardial infarction.

BACKGROUND: Morbidity and mortality after an acute myocardial infarction (AMI) has been reported to be higher in women than men. However, in some prior reports, women were not treated as aggressively as men, suggesting a treatment bias. We sought to determine whether sex influenced short-term outcomes in a cohort of AMI patients, all of whom underwent primary angioplasty. METHODS AND RESULTS: We conducted a retrospective cohort study of all patients undergoing primary angioplasty for a first AMI in New York State in 1995. A total of 1044 patients, 317 women and 727 men, were identified. Mean age was 59+/-12 years in men and 65+/-12 years in women (P<0.05). Women had a higher prevalence of hypertension (59% versus 44%, P<0.05), diabetes (19% versus 14%, P<0.05), and peripheral vascular or carotid disease (9.5% versus 5.5%, P<0.05) than men. Men were more likely to be treated earlier (within 6 hours) from the time of symptom onset than women (74% versus 63%, P<0.05). Women had a higher incidence of shock or hemodynamic instability than men (25% versus 17%, P<0.05). The unadjusted in-hospital mortality rate was 7.9% in women and 2.3% in men (P<0.05). After multivariate logistic regression analysis, women maintained a 2.3-fold higher risk of in-hospital death compared with their male counterparts (95% confidence interval [CI], 1.2 to 4.6, P=0.016). CONCLUSIONS: After correcting for age and baseline risk differences, women undergoing primary angioplasty for AMI have a significantly higher in-hospital mortality rate than men.

Age Factors↗

PubMed2001

Volume-outcome relation for physicians and hospitals performing angioplasty for acute myocardial infarction in New York state.

BACKGROUND: An inverse relation exists between the number of coronary angioplasty procedures performed by physicians or hospitals and short-term mortality. It is not known, however, whether a similar relation holds for physicians and hospitals that perform primary angioplasty for acute myocardial infarction. METHODS AND RESULTS: We analyzed data from the 1995 New York State Coronary Angioplasty Reporting System Registry to determine the relation between the number of primary angioplasty procedures performed by physicians and hospitals and in-hospital mortality. Patients who underwent angioplasty procedures within 23 hours of onset of acute myocardial infarction without preceding thrombolytic therapy were included (n=1342). In-hospital mortality was reduced 57% among patients who underwent primary angioplasty by high-volume as opposed to low-volume physicians (adjusted relative risk 0.43; 95% CI 0.21 to 0.83). When patients with acute myocardial infarction were treated with primary angioplasty in high-volume hospitals rather than low-volume institutions, the relative risk reduction for in-hospital mortality was 44% (adjusted relative risk 0.56; 95% CI 0.29 to 1.1). Compared with patients treated at low-volume hospitals by low-volume physicians, patients treated at high-volume hospitals by high-volume physicians had a 49% reduction in the risk of in-hospital mortality (adjusted relative risk 0.51; 95% CI 0.26 to 0.99). CONCLUSIONS: Among hospitals in New York State, a higher volume of primary angioplasty procedures performed by physicians and/or hospitals was associated with a lower mortality rate.

Angioplasty, Balloon, Coronary↗

PubMed2001