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T T Brown

Publications and source records attributed to T T Brown.

At least 19 recordsLinked to original sources

Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy.

Changes in fat distribution, dyslipidemia, disordered glucose metabolism, and lactic acidosis have emerged as significant challenges to the treatment of human immunodeficiency virus (HIV) infection. Over the past decade, numerous investigations have been conducted to better define these conditions, identify risk factors associated with their development, and test potential therapeutic interventions. The lack of standardized diagnostic criteria, as well as disparate study populations and research methods, have led to conflicting data regarding the diagnosis and treatment of metabolic and body shape disorders associated with HIV infection. On the basis of a review of the medical literature published and/or data presented before April 2006, we have prepared a guide to assist the clinician in the detection and management of these complications.

Dyslipidemias↗

Alternative therapies for osteoporosis.

A variety of common complementary and alternative medicine therapies are now being examined for effectiveness in the management of osteoporosis. Short-term studies in postmenopausal women show beneficial effects of soy isoflavone supplementation on bone density, but its long-term effects require clarification. Prospective controlled trials have shown that physical training can increase bone density to varying degrees. Other therapies that have been examined include herbal formulae, essential fatty acids and vitamins A, C, and K, but few data regarding their effectiveness, mechanisms and safety have been published. Further randomized controlled trials are needed.

Bone Density↗

Neuronal ceroid lipofuscinosis in a Vietnamese pot-bellied pig (Sus scrofa).

The neuronal ceroid ipofuscinoses (NCL) are a group of heritable, neurodegenerative, storage diseases, typically with an autosomal recessive mode of inheritance. Cytoplasmic accumulation of storage material in cells of the nervous system and, variably in other tissues, characterizes NCL. NCL has been reported in many animal species, but to the authors' knowledge, this is the first report of the disease in a pig. Blindness and seizures are common clinical signs of disease, neither of which was a feature in this pig. The lesions were restricted to the central nervous system, which was diffusely affected, with the most severe lesions in the hippocampus, cerebral cortex, and cerebellum. The histologic lesions included neuronal loss and gliosis, which contributed to mild cerebrocortical and cerebellar atrophy and accumulation of autofluorescent storage material in neurons and glial cells. The storage material had morphologic, histologic, and ultrastructural properties typical of NCL.

Animals↗

Feline systemic reactive angioendotheliomatosis: eight cases and literature review.

A rare, multisystemic intravascular proliferative disorder was identified postmortem in eight cats. The majority of these cats died or were euthanized following episodes of dyspnea, lethargy, and anorexia. Microscopic examination revealed occlusive, intraluminal proliferations of spindle cells within small vessels. The heart was consistently involved, and myocardial dysfunction was the probable cause of illness in all cats. Immunohistochemically, the majority of intravascular cells expressed von Willebrand factor, and a smaller number expressed smooth muscle actin, compatible with a dual population of endothelial cells and pericytes, suggesting a reactive rather than a neoplastic process. Four cases of a similar feline vascular disorder from the veterinary literature are reviewed. The histopathology resembles reactive angioendotheliomatosis in humans, a benign cutaneous intravascular endothelial and pericytic proliferative condition. However, in contrast, this feline disease is multisystemic and fatal. We propose the name "feline systemic reactive angioendotheliomatosis" for this unique, idiopathic disorder of domestic cats.

Animals↗

Thymocyte and peripheral blood T lymphocyte subpopulation changes in piglets following in utero infection with porcine reproductive and respiratory syndrome virus.

Piglets infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV) are born severely immunocompromised. In this article we more closely examine the effects of in utero PRRSV infection on circulating and thymic T cell populations. Numbers of CD4+, CD8+, and dual-positive lymphocytes were quantitated in circulation and in the thymus during the 2 weeks following birth. At birth we found that the number of circulating lymphocytes was suppressed by 60%. Lymphocyte numbers were also suppressed by 42% at day 7, but by day 14 the number of lymphocytes had rebounded and was actually 47% greater than controls. At birth and day 7, a drop in the number of CD4+ cells could partially explain the suppression we observed, while the rebound in total lymphocyte numbers seen at day 14 was due to a nearly fourfold increase in the number of circulating CD8+ cells. As a result, the normal CD4+:CD8+ ratio of between 1.4 and 2.2 for neonatal pigs was reduced to 0.1-0.5. The thymuses of infected piglets were found to be 50% smaller than those of control pigs and were characterized by cortical involution and severe cortical depletion of thymocytes. Analysis of the population of thymocytes revealed that double-positive thymocytes were suppressed to a greater degree than either single positive subpopulation. In addition, we show that the number of thymocytes undergoing apoptosis was increased twofold in piglets infected with PRRSV. Taken together, these results help explain the dramatic immunosuppression observed in neonatal animals infected in utero with PRRSV.

Animals↗

Immunopathology of Bartonella vinsonii (berkhoffii) in experimentally infected dogs.

Following natural infection with Bartonella, dogs and humans develop comparable disease manifestations including endocarditis, peliosis hepatis, and granulomatous disease. As the immunologic response to infection in these hosts has not been clearly established, data presented here was derived from the experimental infection of six specific pathogen free (SPF) beagles with a known pathogenic strain of Bartonella. Six dogs were inoculated intravenously with 10(9)cfu of B. vinsonii ssp. berkhoffii and six control dogs were injected intravenously with an equivalent volume of sterile saline. Despite production of substantial levels of specific antibody, blood culture and molecular analyses indicated that Bartonella established chronic infection in these dogs. Flow cytometric analysis of monocytes indicated impaired bacterial phagocytosis during chronic Bartonella infection. There was also a sustained decrease in the percentage of CD8+ lymphocytes in the peripheral blood. Moreover, modulation of adhesion molecule expression (downregulation of L-selectin, VLA-4, and LFA-1) on CD8+ lymphocytes suggested quantitative and qualitative impairment of this cell subset in Bartonella-infected dogs. When compared with control dogs, flow cytometric analysis of lymph node (LN) cells from B. vinsonii infected dogs revealed an expanded population of CD4+ T cells with an apparent naïve phenotype (CD45RA+/CD62L+/CD49D(dim)). However, fewer B cells from infected dogs expressed cell-surface MHC II, implicating impaired antigen presentation to helper T cells within LN. Taken together, results from this study indicate that B. vinsonii establishes chronic infection in dogs which may result in immune suppression characterized by defects in monocytic phagocytosis, an impaired subset of CD8+ T lymphocytes, and impaired antigen presentation within LN.

Animals↗

Physician preferences for continuing medical education with a focus on the topic of antimicrobial resistance: Society for Healthcare Epidemiology of America.

OBJECTIVE: To determine the type of media preferred for continuing medical education (CME) and to assess the factors that affect physician preferences for CME in general and on the special topic of antimicrobial resistance. DESIGN: A voluntary survey of the membership of the Society for Healthcare Epidemiology of America, Inc. (SHEA). METHODS: SHEA, in collaboration with other medical societies and with technical assistance from the Centers for Disease Control and Prevention, designed and mailed the survey to its membership. The survey included questions about media used, preferred, and of interest to try for CME delivery in general and on the topic of antimicrobial resistance in specific. The survey also included demographic and general questions, such as work environment, percentage of time in direct patient care, and experience treating patients with antimicrobial-resistant pathogens. RESULTS: 225 SHEA members completed the survey. The majority of physicians were in clinical practice (59%) and worked in a hospital (57%). The median year of graduation from medical school was 1979 (range, 1951-1999). CME subject matter (46%) was ranked as the most important factor affecting media preference. Journal articles (52%) were the most frequently used educational medium; local grand rounds (53%) and regional meetings (53%) were the most preferred media. CD-ROM (56%) and the Internet (46%) were selected as media of greatest interest to try. On the topic of antimicrobial resistance, the most frequently used and the preferred medium was journal articles (67% and 87%, respectively). Most (94%) had received an educational update on current antimicrobial resistance issues within the past year. Stratification of the data by graduation date revealed no significant differences in the medical education media used most (F=0.59, degrees of freedom [dfl=4, P=.6715) or preferred by SHEA members in general or on the topic of antimicrobial resistance (F=1.99, df=4, P=.0982). CONCLUSIONS: This study provides an understanding of how physicians learn, prefer to learn, and implement best practices for optimal patient outcomes in decreasing the spread of antimicrobial resistance.

Attitude of Health Personnel↗

Enhanced green fluorescent protein as a marker for localizing murine cytomegalovirus in acute and latent infection.

A recombinant murine cytomegalovirus (mCMV) that expresses enhanced green fluorescent protein (EGFP) under control of the native immediate-early 1/3 promoter was constructed to detect directly sites of viral activity in latent and reactivated infections. The recombinant virus had acute and latent infection characteristics similar to those of wild-type mCMV. Rare green-fluorescing foci were observed in paraffin sections from lungs and spleens infected latently. Positive immunoperoxidase staining for EGFP in sections of the same lung tissues suggests that these cells may be sites of restricted viral gene expression. EGFP was detected easily in tissue explants reactivating from latent infection in vitro. Morphology and adhesion characteristics of fluorescing cells suggest that viral reactivation occurs in tissue macrophages in explant cultures. The observations presented in this study demonstrate the usefulness of EGFP-expressing recombinants as tools for direct tracking of mCMV activity in vivo and in vitro.

Acute Disease↗

Peptide transport system-1 (PTS-1) for Tyr-MIF-1 and Met-enkephalin differs from the receptors for either.

Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and Met-enkephalin share a saturable transport system (peptide transport system-1, PTS-1) across the blood-brain barrier but do not readily bind to each other's receptors. This information allows the unique opportunity to differentiate the transport protein(s) from the receptors for either peptide in brain endothelial cells. PTS-1 was studied in vitro by allowing radiolabeled Tyr-MIF-1 (125I-Tyr-MIF-1) to bind to the solubilized proteins of isolated murine brain microvessels in the presence or absence of potential inhibitors. Sephadex chromatography separated bound from free labeled peptide. The binding was saturable as shown by inhibition with increasing concentrations of unlabeled Tyr-MIF-1. 125I-Tyr-MIF-1 binding was not inhibited by an unrelated peptide or iodo-tyrosine. D-Tyr-MIF-1 had no effect, demonstrating the stereospecificity of the system. Met-enkephalin decreased the binding of 125I-Tyr-MIF-1 to 84.4% of total, whereas Leu-enkephalin was without effect. Agonists for the mu, delta, and kappa opiate receptors did not change the binding, indicating that the proteins which bound to 125I-Tyr-MIF-1 were not endogenous opiate receptors. The results indicate that, in vitro, Tyr-MIF-1 binds to brain microvessel proteins with characteristics similar to PTS-1.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Dental wear and growth performance in steers fed sweetpotato cannery waste.

OBJECTIVE: To determine whether feeding sweetpotato cannery waste (SPCW) to cattle had adverse effects on dental wear, growth performance, or ruminal tissues. DESIGN: Clinical trial. ANIMALS: 36 Holstein steers. PROCEDURE: Steers were assigned to 1 of 3 groups. All steers received ryegrass hay ad libitum. In addition, steers in group 1 were fed 3.2 kg of corn and soybean meal/steer/d, steers in group 2 were fed 0.45 kg of soybean meal/steer/d and SPCW ad libitum, and steers in group 3 were fed a mixture of SPCW and broiler litter ad libitum. Samples of rumen fluid were collected on day 56. Steers were slaughtered on day 84, and samples of rumen were submitted for histologic examination. Teeth from control steers were removed, and calcium ion loss in response to etching with 2.28% lactic acid solutions buffered to pH of 3.75, 4.0, 4.25, 4.5, and 4.75 was determined. RESULTS: Average daily gain was lower for steers fed SPCW than for steers in the other 2 groups. Steers fed the SPCW-broiler litter mixture had only mild increases in tooth wear and tooth color scores, compared with control steers, whereas steers fed unbuffered SPCW had substantial increases in tooth wear and tooth color scores. Histologic abnormalities were detected in rumens from steers fed diets containing SPCW. Calcium ion loss decreased as pH of the etching solution increased. CLINICAL IMPLICATIONS: Results indicate that feeding cattle unbuffered SPCW can cause dental erosion, ruminal epithelial changes, and poor growth; however, SPCW buffered with broiler litter can be used as a cattle feed.

Ammonia↗

Bartonella vinsonii subsp. berkhoffii and related members of the alpha subdivision of the Proteobacteria in dogs with cardiac arrhythmias, endocarditis, or myocarditis.

Cardiac arrhythmias, endocarditis, or myocarditis was identified in 12 dogs, of which 11 were seroreactive to Bartonella vinsonii subspecies berkhoffii antigens. Historical abnormalities were highly variable but frequently included substantial weight loss, syncope, collapse, or sudden death. Fever was an infrequently detected abnormality. Cardiac disease was diagnosed following an illness of short duration in most dogs, but a protracted illness of at least 6 months' duration was reported for four dogs. Valvular endocarditis was diagnosed echocardiographically or histologically in eight dogs, two of which also had moderate to severe multifocal myocarditis. Four dogs lacking definitive evidence of endocarditis were included because of seroreactivity to B. vinsonii antigens and uncharacterized heart murmurs and/or arrhythmias. Alpha proteobacteria were not isolated from the blood by either conventional or lysis centrifugation blood culture techniques. Using PCR amplification and DNA sequencing of a portion of the 16S rRNA gene, B. vinsonii was identified in the blood or heart valves of three dogs. DNA sequence alignment of PCR amplicons derived from blood or tissue samples from seven dogs clustered among members of the alpha subdivision of the Proteobacteria and suggested the possibility of involvement of one or more alpha proteobacteria; however, because of the limited quantity of sequence, the genus could not be identified. Serologic or molecular evidence of coinfection with tick-transmitted pathogens, including Ehrlichia canis, Babesia canis, Babesia gibsonii, or spotted fever group rickettsiae, was obtained for seven dogs. We conclude that B. vinsonii subsp. berkhoffii and closely related species of alpha proteobacteria are an important, previously unrecognized cause of arrhythmias, endocarditis, myocarditis, syncope, and sudden death in dogs.

Alphaproteobacteria↗

Clinical and pathologic evaluation of chronic Bartonella henselae or Bartonella clarridgeiae infection in cats.

Human Bartonella infections result in diverse medical presentations, whereas many cats appear to tolerate chronic bacteremia without obvious clinical abnormalities. Eighteen specific-pathogen-free cats were inoculated with Bartonella henselae- and/or Bartonella clarridgeiae-infected cat blood and monitored for 454 days. Relapsing bacteremia did not correlate with changes in protein profiles or differences in antigenic protein recognition. Intradermal skin testing did not induce a delayed type hypersensitivity reaction to cat scratch disease skin test antigen. Thirteen cats were euthanatized at the end of the study. Despite persistent infection, clinical signs were minimal and gross necropsy results were unremarkable. Histopathology revealed peripheral lymph node hyperplasia (in all of the 13 cats), splenic follicular hyperplasia (in 9 cats), lymphocytic cholangitis/pericholangitis (in 9 cats), lymphocytic hepatitis (in 6 cats), lymphoplasmacytic myocarditis (in 8 cats), and interstitial lymphocytic nephritis (in 4 cats). Structures suggestive of Bartonella were visualized in some Warthin-Starry stained sections, and Bartonella DNA was amplified from the lymph node (from 6 of the 13 cats), liver (from 11 cats) heart (from 8 cats), kidney (from 9 cats), lung (from 2 cats), and brain (from 9 cats). This study indicates that B. henselae or B. clarridgeiae can induce chronic infection following blood transfusion in specific-pathogen-free cats and that Bartonella DNA can be detected in blood, brain, lymph node, myocardium, liver, and kidney tissues of both blood culture-positive cats and blood culture-negative cats. Detection of histologic changes in these cats supports a potential etiologic role for Bartonella species in several idiopathic disease processes in cats.

Animals↗

Proliferation and differentiation defects during lung development in corticotropin-releasing hormone-deficient mice.

Corticotropin-releasing hormone-deficient (CRH-KO) mice, which as a consequence are also glucocorticoid-insufficient, exhibit neonatal lethality when derived from CRH-KO mothers. Death is due to respiratory insufficiency as a result of abnormal pulmonary development, and can be prevented by prenatal administration of glucocorticoids. In the study described here, we used CRH-KO mice as a model of genetically altered in utero glucocorticoid action to elucidate the role of endogenous glucocorticoids in lung maturation. The histologic appearance of the lungs of these mice is normal until Day 17.5 of gestation, at which point failure of septal thinning and air-space formation is observed. These morphologic alterations in the CRH-KO mouse lung are the result of continued cell division in cellular compartments that by this time in gestation have ceased proliferating in wild-type mice, rather than the result of a failure of apoptosis. In accord with this observation, the CRH-KO lung exhibits delayed induction of type II pneumocyte biochemical parameters, such as messenger RNAs (mRNAs) for surfactant protein-A (SP-A) and SP-B, and fatty acid synthase, as well as delayed Clara cell maturation. In contrast, surfactant phospholipid synthesis is not impaired during CRH-KO lung development. Our findings indicate that an essential role of endogenous glucocorticoids in pulmonary maturation in utero is to stimulate a developmental program in late gestation that affects epithelial and mesenchymal cell proliferation and differentiation throughout the parenchyma.

Animals↗

Effect of breed (Angus vs Simmental) on immune function and response to a disease challenge in stressed steers and preweaned calves.

Two experiments were conducted with feeder steer calves and preweaned calves to determine the effects of breed on immune response. In Exp. 1, newly weaned Angus (n = 24) and Simmental (n = 24) steer calves were blocked by weight within breed and randomly assigned to 12 pens with four calves per pen. The basal diet consisted of 87% corn silage (DM basis) and 13% of a soybean meal-mineral-vitamin supplement. Steers were allowed ad libitum access to feed throughout the study. On d 2 following weaning, calves received an intranasal inoculation of infectious bovine rhinotraecheitis virus (IBRV; 2.7 x 10(8) CCID50). Rectal temperatures in response to the IBRV were higher (P < .05) in Angus calves. On d 9, calves were injected i.m. with 10 mL of a 25% pig red blood cell (PRBC) suspension. Total immunoglobulin (Ig) and IgM titers against PRBC were higher (P < .05) for the Angus calves. Breed did affect cell-mediated immune response to phytohemagglutinin (PHA). In Exp. 2, preweaned (16 Angus and 16 Simmental) calves were selected based on breed, body weight, and sex. On 0 d, all selected calves were injected i.m. with 10 mL of a 25% PRBC suspension. Total Ig and IgG titers against PRBC were higher (P < .05) for Angus calves. On d 28, lymphocytes were isolated from peripheral blood obtained from eight calves per breed. Peripheral lymphocytes from the Angus calves had a greater (P < .07) blastogenic response to 6.25 microg/mL of PHA than lymphocytes from Simmental calves. Results indicate that the immune response of Angus and Simmental calves may differ.

Animals↗

Neurodevelopmental dysfunction among nonreferred children with idiopathic megalencephaly.

PURPOSE: To determine whether nonreferred children with idiopathic megalencephaly show evidence of specific neurodevelopmental dysfunction compared with sibling control subjects and age-matched control subjects. DESIGN: Cross-sectional, case-control study in a large, suburban pediatric practice. Subjects included 20 children between the ages of 6 and 15 years with a head circumference at greater than the 98th percentile, 19 siblings of these children with normalsize heads, and 16 age-matched control subjects. Standardized tests of language, academic achievement, visuomotor integration, motor function, and neurodevelopmental function were administered. RESULTS: Multivariate analysis, with control for age, showed a main effect for the presence of megalencephaly (F = 3.2; p < 0.05). Follow-up univariate analyses, with control for age, showed that children with megalencephaly had poorer performance on tasks of upper limb speed, visuomotor control, running speed, bilateral coordination, visuomotor integration, naming fluency, and minor neurologic indicators. CONCLUSION: The relationship between idiopathic megalencephaly and external hydrocephalus in infants is discussed. Results show that so-called "benign" idiopathic megalencephaly in nonreferred school-age children appears to be a clinical entity associated with subtle motor problems and neurodevelopmental dysfunction.

Achievement↗

Exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala) with pancreatic adenocarcinoma.

This report describes exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala) with complete effacement of the pancreas by a pancreatic adenocarcinoma. The bird presented with a 3-month history of weight loss and voluminous, foul-smelling droppings. Clinically, routine hematologic findings were normal and fecal tests were performed to evaluate exocrine pancreatic function. The fecal function tests were positive for neutral and split fats and negative for trypsin. Oral administration of corn oil did not result in elevation of blood triglyceride levels. Two days later, the triglyceride tolerance test was repeated using corn oil mixed with pancreatic enzymes. This time, there was a 70% elevation of blood triglyceride levels. Because of a poor prognosis, the bird was euthanatized. At necropsy, the pancreas was diffusely enlarged, white, nodular, and firm. The liver contained multiple, 1-2-mm-diameter, randomly located, tan nodules. Microscopically, the pancreas was effaced by numerous lobules of neoplastic ductular structures surrounded by abundant fibrous connective tissue. In the liver, the hepatic parenchyma was replaced by multiple, well-demarcated, nonencapsulated foci of neoplastic tissue similar to that in the pancreas.

Adenocarcinoma↗

Effects of copper deficiency and copper deficiency coupled with high dietary iron or molybdenum on phagocytic cell function and response of calves to a respiratory disease challenge.

A study was conducted to determine the effects of supplementing a diet marginally deficient in copper (Cu) with iron (Fe), molybdenum (Mo), or Cu on phagocytic cell function and disease resistance of calves. Thirty-one calves were born to heifers fed a corn silage-based diet containing 4.5 mg of Cu/kg. Treatments consisted of 1) control (CON; no supplemental Cu, Fe, or Mo), 2) 600 mg of Fe added/kg (FE), 3) 5 mg of Mo added/kg (MO), or 4) 10 mg of Cu added/kg of DM (CU). Activity of superoxide dismutase was lower (P < .06) in neutrophils from MO vs CON or CU calves at 170 d of age. bactericidal activity of neutrophils from MO calves tended (P = .15) to be lower compared with those from CU calves at 70 d of age. Calves were inoculated intranasally with live infectious bovine rhinotracheitis virus (IBRV) 2 d after weaning, followed by intratracheal administration of Pasteurella hemolytica 5 d later. Iron- and Cu-supplemented calves exhibited higher (P < .01) body temperatures and lower (P < .06) feed intakes following IBRV inoculation compared with CON and MO calves. Copper-supplemented calves had higher levels of plasma tumor necrosis factor (TNF) than MO calves at weaning (P < .05) and tended to have higher plasma TNF (P = .11) than FE and MO calves 5 d after IBRV inoculation. These data indicate that dietary levels of Mo and Cu can affect body temperature and feed intake responses to disease by affecting TNF and perhaps other cytokines.

Aging↗

Effect of shipping and chromium supplementation on performance, immune response, and disease resistance of steers.

Forty-eight Angus crossbred steers (263 +/- 2 kg initial BW) were blocked by weight and randomly assigned within weight group to treatment. Treatments consisted of control or .4 mg of supplemental Cr as Cr-nicotinic acid complex/kg of DM. Steers were fed diets containing 90% corn silage (DM basis) and 10% of a soybean meal-mineral-vitamin supplement. After 56 d on the dietary treatment, half of the steers in each treatment were transported 343 km and unloaded in an unfamiliar location. The next day, d 58, shipped steers were returned to the feedlot (50 km). On d 58 after shipped steers were returned to the feedlot, all steers were inoculated with infectious bovine rhinotracheitis virus (IBRV) intranasally. Average daily gain from d 0 to 80 was increased (P < .10) by supplemental Cr. There was a shipping x time interaction for serum cortisol concentrations. Shipping increased (P < .02) serum cortisol on d 58, but 7 d after transport there were no effects of shipping on serum cortisol. Transportation increased (P < .05) the ratio of neutrophils to lymphocytes. Supplemental Cr did not affect rectal temperature after the IBRV challenge or the antibody response to IBRV or porcine red blood cells. Immunoglobulin G antibody response to porcine red blood cells was decreased (P < .09) by shipping. Supplemental Cr as Cr-nicotinic acid improved ADG of growing steers, regardless of whether they had been stressed by shipping. Supplemental Cr did not affect any of the immune responses that were measured.

Animals↗