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Robert J Adams

Publications and source records attributed to Robert J Adams.

69 records · Page 4Linked to original sources
PubMed2003

Elevated peripheral benzodiazepine receptor expression in simian immunodeficiency virus encephalitis.

Measurement of central nervous system (CNS) expression of the peripheral benzodiazepine receptor (PBR), a microglia and macrophage activation marker, by positron emission tomography (PET) would aid clinical management of human immunodeficiency virus (HIV)-infected patients. To evaluate the utility of examining PBR expression in the CNS as a cellular activation marker in HIV CNS disease, PBR levels were measured in frontal cortex of simian immunodeficiency virus (SIV)-infected macaques with encephalitis and uninfected animals via PK11195 ligand autoradiography. [(3)H]-(R)-PK11195 binding to both grey matter (P =.017) and white matter (P =.038) was significantly higher in animals with SIV encephalitis (n = 10) versus control animals (n = 3). When PK11195 binding was compared with other microglial/macrophage activation markers (obtained via quantitative image analysis), a strong, significant association was found for both HAM56 (P =.004) and KP-1 (anti-CD68; P =.006) immunostaining in white matter. In contrast, grey matter PK11195 binding did not correlate with HAM56 (P =.46), KP-1 (P =.06), or glial fibrillary acidic protein (GFAP) immunostaining for astrocytic activation (P =.09). The regional nature of these increases in activation within the brain illustrates the crucial need to focus functional neuroimaging analyses of HIV-infected individuals on subcortical white matter to assess activation of microglia and macrophages.

Animals↗
PubMed2003

Central nervous system correlates of behavioral deficits following simian immunodeficiency virus infection.

Despite the high incidence of cognitive and motor impairment in acquired immunodeficiency syndrome (AIDS) patients, the mechanisms of AIDS-related central nervous system (CNS) pathology are not completely understood. Infection with simian immunodeficiency virus (SIV) in macaques provides an excellent model of AIDS, including human immunodeficiency virus (HIV)-induced CNS pathology and cognitive/behavioral impairment. Co-inoculation with two SIV strains, SIV/17E-Fr and SIV/DeltaB670, accelerates SIV CNS disease, producing SIV encephalitis in over 90% of pig-tailed macaques within 3 months. In the present study, this SIV model was employed to identify cellular and viral correlates of behavioral impairment following SIV infection. Measures of psychomotor speed (simple reaction time), fine motor control (bimanual motor task), and general motor activity (home cage movement) were all adversely affected by SIV disease. Prior to euthanasia, performance was significantly impaired in both a simple reaction time task in 6 of 12 monkeys and a bimanual motor task in 5 of 6 monkeys. All monkeys evaluated (11 of 11) showed significant reductions in spontaneous motor activity. Significant correlations were found between impaired performance on the bimanual motor test and axonal damage (accumulation of beta-amyloid precursor protein in the corpus callosum) as well as increased microglial activation and macrophage infiltration (levels of CD68 and Ham56 immunostaining). These results suggest that axonal damage is related to the behavioral impairment induced by infection with SIV. The axonal damage may result from neuroimmune responses, including microglial and macrophage activation. Therefore, axonal damage may be a morphologic manifestation of neuronal dysfunction that underlies development of behavioral impairment in HIV/SIV CNS infection.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Adverse drug events and medication errors in Australia.

PURPOSE: To review information about adverse drug events (ADEs) and medication errors in Australia. DATA SOURCES: Systematic literature reviews and reports from data collections of the Australian Bureau of Statistics, Institute of Health and Welfare, Council for Health Care Standards and Patient Safety Foundation. RESULTS: (medical record reviews): We have shown that 2-4% of all hospital admissions, and up to 30% for patients > 75 years of age, are medication-related; up to three-quarters are potentially preventable. RESULTS (routine data collections): Routine death certificate and hospital discharge data coded using the International Classification of Diseases capture less than half as many ADEs as medical record reviews. Of coded adverse events that contributed to death, 27% involved an ADE, as did 20% of adverse events identified at discharge and 43% at general practice encounters. There is a strong correlation between increases in medication use and rates of adverse drug reactions (ADRs) associated with hospitalization. RESULTS (drugs implicated): These were similar in all the above studies: anticoagulants, anti-inflammatory drugs, opioids, anti-neoplastics, antihypertensives, antibiotics, cardiac glycosides, diuretics, hypoglycaemic agents, steroids, hypnotics, anticonvulsants, and antipsychotics. RESULTS (clinical indicators): An ADE is reported in 1% of hospital admissions, while some hospitals do not report ADRs to the national collection. Only three-quarters of patients with acute myocardial infarction receive thrombolytics within 1 hour of presentation. Five per cent of patients on warfarin record an international normalized ratio > 5, and 1%, 0.05%, and 0.2% -suffer abnormal bleeding, cerebral haemorrhage, or death, respectively. RESULTS (the Australian Incident Monitoring System): Twenty-six per cent of 27 000 hospital-related incidents were medication-related, as were 36% of 2000 anaesthesia-related incidents, and 50% of 2500 general practice incidents. RESULTS (errors): Errors occur in 15-20% of drug administrations when ward stock systems are used and 5-8% when individual patient systems are used. Previous allergic reactions to drugs may not be recorded more than 75% of the time. CONCLUSION: ADEs are common in the Australian health system. Anticoagulant, anti-inflammatory, and cardiovascular drugs feature prominently as preventable, high impact problems, and collectively make up over one-half of all ADEs. Methods for monitoring and preventing ADEs should be progressively improved.

Australia↗
PubMed2003

Alpha Thalassemia is associated with decreased risk of abnormal transcranial Doppler ultrasonography in children with sickle cell anemia.

PURPOSE: Cerebrovascular complications of sickle cell disease (SCD) are common, but the risk factors remain unclear. The multicenter Stroke Prevention Trial in Sickle Cell Anemia (STOP) provided an opportunity to examine alpha thalassemia-2 as a modifying risk factor, using abnormal transcranial Doppler ultrasonography (TCD) as a surrogate marker for cerebrovascular disease. The authors hypothesized that children with abnormal TCD are less likely to have alpha thalassemia-2, and an increased hemoglobin level accounts for this protective effect. METHODS: A retrospective study was conducted of children with SCD who had both alpha gene and TCD data from STOP: 128 with TCD of at least 200 cm/s (abnormal TCD) and 172 with TCD less than 170 cm/s (normal TCD). RESULTS: Alpha thalassemia-2 was more frequent in the normal TCD group compared with the abnormal TCD group. The odds ratio for normal TCD and alpha thalassemia-2 was 4.1. Adjusting for either hemoglobin level or red cell size (mean corpuscular volume) reduced the odds ratio only slightly. Age, normal TCD, and alpha thalassemia-2 had significant statistical interaction, so that alpha thalassemia-2 was not related to TCD for age 10 years or older. CONCLUSIONS: The frequency of alpha thalassemia-2 was significantly higher in children with normal TCD. Speculation on mechanisms of effect includes improved erythrocyte deformability, reduced red cell adhesion, and reduced nitric oxide scavenging in alpha thalassemia-2. The association of alpha thalassemia-2 and normal TCD adds to the evidence on the protective effects of alpha thalassemia-2 in SCD and highlights the contribution of epistatic factors.

Anemia, Sickle Cell↗
PubMed2003

The effect of treatment of allergic rhinitis on asthma morbidity, including emergency department visits.

PURPOSE OF REVIEW: It has been hypothesized that asthma and allergic rhinitis are both manifestations of a single inflammatory process present throughout the airway and that control of the inflammatory response associated with allergic rhinitis may help to reduce inflammation throughout the airway and improve control of asthma. Although previous evidence has documented that therapy directed at allergic rhinitis can improve asthma symptoms and bronchial responsiveness, until recently, there was no evidence that the use of medication targeted at the upper airway can also reduce utilization of acute health care services due to asthma. RECENT FINDINGS: We identified studies published between August 2001 and July 2002 that examined the therapeutic link between allergic rhinitis and asthma. In particular, we concentrated on investigations that evaluated whether, among patients diagnosed with allergic rhinitis and asthma, treatment of the former resulted in significantly fewer asthma-related emergency department visits or inpatient hospitalizations. Two such studies were identified. Using observational study designs, both investigations established that among a population with asthma and allergic rhinitis, treatment for allergic rhinitis was associated with a decrease in the risk of subsequent asthma-related events by one-third to one-half compared with persons who did not receive treatment for this disorder. SUMMARY: Effective management of allergic rhinitis with nasal steroids and possibly oral antihistamines reduces utilization of acute health care services due to asthma among persons with co-existent asthma.

Adolescent↗
PubMed2003

Hemoglobinopathies.

The outlook for patients with sickle cell disease has improved steadily during the last two decades. In spite of these improvements, curative therapies are currently available only to a small minority of patients. The main theme of this chapter is to describe new therapeutic options that are at different stages of development that might result in further improvements in the outlook for patients with these disorders. Dr. Joseph DeSimone and his colleagues had previously made the important observation that the hypomethylating agent 5-azacytidine can reverse the switch from adult to fetal hemoglobin in adult baboons. Although similar activity was demonstrated in patients with sickle cell disease and beta-thalassemia, concern about the toxicity of 5-azacytidine prevented its widespread use in these disorders. In Section I, Dr. DeSimone discusses the role of DNA methylation in globin gene regulation and describe recent clinical experience with decitabine (an analogue of 5-azacytidine) in patients with sickle cell disease. These encouraging studies demonstrate significant fetal hemoglobin inducing activity of decitabine in patients who fail to respond to hydroxyurea. In Section II, Dr. George Atweh continues the same theme by describing recent progress in the study of butyrate, another inducer of fetal hemoglobin, in patients with sickle cell disease and beta-thalassemia. The main focus of his section is on the use of a combination of butyrate and hydroxyurea to achieve higher levels of fetal hemoglobin that might be necessary for complete amelioration of the clinical manifestations of these disorders. Dr. Atweh also describes novel laboratory studies that shed new light on the mechanisms of fetal hemoglobin induction by butyrate. In Section III, Dr. Ronald Nagel discusses the different available transgenic sickle mice as experimental models for human sickle cell disease. These experimental models have already had a significant impact on our understanding of the pathophysiology of sickle cell disease. Dr. Nagel describes more recent studies in which transgenic sickle mice provide the first proof of principle that globin gene transfer into hematopoietic stem cells inhibits in vivo sickling and ameliorates the severity of the disease. Although stroke in adult patients with sickle cell disease is not as common as in children, adult hematologists, like their pediatric colleagues, need to make management decisions in adult patients with a stroke or a history of stroke. Dr. Robert Adams has led several large clinical studies that investigated the role of transfusions in the prevention of stroke in children with sickle cell disease. Much less is known, however, about the prevention of first or subsequent strokes in adult patients with sickle cell disease. In Section IV, Dr. Adams provides some general guidelines for the management of adult patients with stroke while carefully distinguishing between recommendations that are evidence-based and those that are anecdotal in nature.

Animals↗
PubMed2002

The burden of asthma in the United States: level and distribution are dependent on interpretation of the national asthma education and prevention program guidelines.

Asthma imposes a growing burden on society in terms of morbidity, quality of life, and healthcare costs. Although federally sponsored national surveys provide estimates of asthma prevalence, these surveys are not designed to characterize the burden of asthma by self-reported disease activity. We sought to characterize asthma burden in the United States. This study was based on a cross-sectional random-digit-dial household telephone survey designed to identify adult patients and parents of children with current asthma. Global asthma burden was comprised of three components: short-term symptom burden (4-week recall), long-term symptom burden (past year), and functional impact (activity limitation). Using this construct, only 10.7% of individuals were classified as having a global asthma burden consistent with mild intermittent disease, and 77.3% had moderate to severe persistent disease. These results suggest that a majority of the United States population with asthma experiences persistent rather than intermittent asthma burden. In addition, the discordance in type and distribution of asthma symptoms reported by individual subjects suggests that the exact estimate of the burden of asthma is related to how the National Asthma Education and Prevention Program classification is operationalized. Inquiry into recent day or nighttime symptoms alone underestimates the burden of asthma and may lead to inadequate treatment of asthma based on national guideline recommendations.

Adolescent↗
PubMed2002

Sickle cell disease: the neurological complications.

The genetic cause of sickle cell disease has been known for decades, yet the reasons for its clinical variability are not fully understood. The neurological complications result from one point mutation that causes vasculopathy of both large and small vessels. Anemia and the resultant cerebral hyperemia produce conditions of hemodynamic insufficiency. Sickled cells adhere to the endothelium, contributing to a cascade of activated inflammatory cells and clotting factors, which result in a nidus for thrombus formation. Because the cerebrovascular reserve becomes exhausted, the capacity for compensatory cerebral mechanisms is severely limited. There is evidence of small-vessel sludging, and a relative deficiency of nitric oxide in these vessels further reduces compensatory vasodilatation. Both clinical strokes and silent infarcts occur, affecting motor and cognitive function. New data suggest that, in addition to sickle cell disease, other factors, both environmental (eg, hypoxia and inflammation) and genetic (eg, mutations resulting in thrombogenesis), may contribute to a patient's stroke risk. The stroke risk is polygenic, and sickle cell disease can be considered a model for all cerebrovascular disease. This complex disease underscores the potential intellectual and practical distance between the determination of molecular genetics and effective clinical application and therapeutics.

Anemia, Sickle Cell↗
PubMed2002

Deposition and expression of aerosolized rAAV vectors in the lungs of Rhesus macaques.

The goals of these experiments were to efficiently deliver aerosolized adeno-associated virus (AAV) vector to the lungs of Rhesus macaques and to measure gene transfer and expression. To determine optimal lung deposition, we compared four techniques of delivering aerosolized saline admixed with the radioisotope (99m)technetium ((99m)Tc) nebulized through a mouthpiece (Neb Oral), a laryngeal airway mask (Neb LMA), or an endotracheal tube (Neb ETT), or bronchoscopically delivered by Microsprayer (PennCentury). Total lung deposition fraction, as indicated by gamma scintigraphy, averaged 0.5% (Neb Oral), 1.2% (Neb LMA), 1.8+/-0.4% (Neb ETT), and 62.3+/-11.3% (Microsprayer). Because microspraying was the most efficient method of delivery, we used it to administer saline with (99m)Tc-labeled diethylene-triamine penta-acetic acid (DTPA) admixed with 9 x 10(11) infectious units (i.u.) of AAV serotype 2 (rAAV2) vector encoding green fluorescent protein (GFP; rAAV2-GFP). Initial total and regional lung depositions were quantified by scintigraphy. We analyzed the tissue three weeks later for vector-specific DNA transduction and RNA expression. Radioisotope was detected in all lung regions, reflecting an average dose of 1.33 x 10(10)+/-9.5 x 10(9) i.u. per region. Regional data indicated an increase in expression when the dose exceeded 3 x 10(9) i.u. (P=0.030). We conclude that expression of rAAV2-GFP in lungs appears to be related to depositing a regional threshold dose greater than 3 x 10(9) i.u., easily achieved by bronchoscopic microspraying.

Administration, Inhalation↗
PubMed2002

Intranasal steroids and the risk of emergency department visits for asthma.

BACKGROUND: In patients with asthma, treatment for associated conditions, such as rhinitis, is recommended. It is unknown whether this treatment can reduce the risk for emergency department (ED) visits for asthma. OBJECTIVES: We sought to determine whether treatment with intranasal steroids or prescription antihistamines in persons with asthma is associated with a reduced risk for ED visits caused by asthma. METHODS: We performed a retrospective cohort study of members of a managed care organization aged greater than 5 years who were identified during the period of October 1991 to September 1994 as having a diagnosis of asthma by using a computerized medical record system. The main outcome measure was an ED visit for asthma. RESULTS: Of the 13,844 eligible persons, 1031 (7.4%) had an ED visit for asthma. The overall relative risk (RR) for an ED visit among those who received intranasal corticosteroids, adjusted for age, sex, frequency of orally inhaled corticosteroid and beta-agonist dispensing, amount and type of ambulatory care for asthma, and diagnosis of an upper airways condition (rhinitis, sinusitis, or otitis media), was 0.7 (95% confidence interval [CI], 0.59-0.94). For those receiving prescription antihistamines, the risk was indeterminate (RR, 0.9; 95% CI, 0.78-1.11). When different rates of dispensing for intranasal steroids were examined, a reduced risk was seen in ED visits in those with greater than 0 to 1 (RR, 0.7; 95% CI, 0.57-0.99) and greater than 3 (RR, 0.5; 95% CI, 0.23-1.05) dispensed prescriptions per year. CONCLUSIONS: Treatment of nasal conditions, particularly with intranasal steroids, confers significant protection against exacerbations of asthma leading to ED visits for asthma. These results support the use of intranasal steroids by individuals with asthma and upper airways conditions.

Administration, Intranasal↗
PubMed2002

Inadequate use of asthma medication in the United States: results of the asthma in America national population survey.

BACKGROUND: Studies of the use of anti-inflammatory asthma therapy have been limited to selected populations or have been unable to assess the appropriateness of therapy for individuals. OBJECTIVE: We sought to describe the current use of asthma medication in the United States population and to examine the influence of symptoms and sociodemographics on medication use. METHODS: This study was based on a cross-sectional, national, random-digit-dial household telephone survey in 1998 designed to identify adult patients and parents of children with current asthma. Respondents were classified as having current asthma if they had a physician's diagnosis of asthma and were either taking medication for asthma or had asthma symptoms during the past year. RESULTS: One or more persons met the study criteria for current asthma in 3273 (7.8%) households in which a screening questionnaire was completed. Of these, 2509 persons (721 children <16 years) with current asthma were interviewed. Current use of anti-inflammatory medication was reported by 507 (20.1%). Of these, most were using inhaled corticosteroids (72.5%), with use of antileukotrienes reported by 11.4% and use of cromolyn-nedocromil reported by 18.6%. Of persons with persistent asthma symptoms in the past month, 26.2% reported current use of some form of anti-inflammatory medication. In bivariate analysis persons reporting lower income, less education, and present unemployment, as well as smokers, were significantly (P <.001) less likely to report current anti-inflammatory use than were other populations. In a multiple regression model nonsmokers and those of white, non-Hispanic ethnicity, as well as persons reporting less asthma control, were more likely to report current anti-inflammatory medication use. CONCLUSION: In the United States use of appropriate asthma therapy remains inadequate. Strategies to increase use of anti-inflammatory therapy among patients with asthma are needed. These might include methods to increase access to asthma care for minorities and the socioeconomically disadvantaged.

Adolescent↗
PubMed2002

Longitudinal changes in ferritin during chronic transfusion: a report from the Stroke Prevention Trial in Sickle Cell Anemia (STOP).

PURPOSE: Chronic red cell transfusion has been used for prevention of recurrent stroke in patients with sickle cell disease for three decades, and its effectiveness in primary prevention was recently shown. Iron overload, the inevitable result of chronic transfusion, is commonly monitored with serum ferritin concentration. PATIENTS AND METHODS: Sixty-one patients at high risk for stroke received chronic transfusion in a clinical trial of stroke prevention. A serum ferritin level of less than 500 ng/mL was required for study entry. Ferritin levels were obtained quarterly. Fifty patients who had four or more ferritin measurements were included in this analysis. Transfusions were administered as exchange or simple, with washed, reconstituted, or packed red blood cells, at the discretion of the site investigator. RESULTS: Serum ferritin levels increased linearly with cumulative transfusion volume during the first four ferritin measurements, but the rate of increase varied widely among patients. Rates of increase varied similarly among 23 patients who received exclusively simple transfusion with packed red cells and in five patients who received exchange transfusions. Thirty-two patients received a total transfusion volume of more than 250 mL/kg. Ferritin continued to increase linearly after the first four measurements in 14, but the remaining 18 experienced a plateau before the level reached 3,000 ng/mL. Six of those with a linear increase never reached a ferritin level of 3,000 ng/dL. CONCLUSIONS: There was strong intrapatient correlation between serum ferritin levels and volume transfused but wide interpatient variability early during chronic transfusion therapy. Intrapatient correlation declined at transfusion volumes of more than 250 mL/kg. Direct iron store assessment is needed to determine the clinical significance of serum ferritin variability.

Adolescent↗
PubMed2002

Unusual encephalopathy after acute chest syndrome in sickle cell disease: acute necrotizing encephalitis.

Stroke is the most common neurologic complication of sickle cell disease. Acute chest syndrome (ACS) is a known risk factor for stroke in this population. Two patients (a 12-year-old boy and a 6-year-old girl) developed acute change of mental status and focal neurologic signs during episodes of ACS. The clinical and radiologic findings were compatible with acute necrotizing encephalitis, a variant of acute demyelinating encephalomyelitis. Patients with acute neurologic deterioration in conjunction with ACS should be evaluated thoroughly for other causes of central nervous system disease including infectious/parainfectious processes as well as stroke.

Acyclovir↗