Biomedical subjects

J Billings

Publications and source records attributed to J Billings.

At least 19 recordsLinked to original sources

PubMed1997

Rapid assay of plasma brain natriuretic peptide in the assessment of acute dyspnoea.

AIM: Recognition of heart failure may be difficult in patients presenting with acute dyspnoea, particularly in the presence of chronic airways obstruction or obesity. In a previous study of patients with acute dyspnoea, we showed that the measurement of plasma brain natriuretic peptide (BNP)-a hormone secreted in increased amounts by the failing heart-accurately distinguishes heart failure from primary lung disorder. The aim of the present study was to develop a rapid assay for BNP and evaluate its diagnostic use in patients acutely hospitalised for increasing dyspnoea of any cause. METHODS: A rapid assay for plasma BNP, providing results within 24 h of blood collection, was developed without loss of precision. The results of the rapid and previously established BNP assays were highly correlated (r = 0.9). To determine the diagnostic value of the rapid assay, measurements were undertaken on the day of admission in 123 breathless patients (mean age 68.3, range 23 to 90 years) and related to conventional diagnostic assessments and final outcome. RESULTS: In patients diagnosed and treated urgently for clinical heart failure, plasma BNP was significantly higher (115 (SE 13) pmol/L, n = 39) than in those without clinical heart failure (33 (5) pmol/L, n = 84, p < 0.001). Using a cut-off of 50 pmol/L for the presence of heart failure, there was discordance between BNP level and clinical diagnosis in 21 of 123 cases. Reassessment after independent analysis of discordant cases increased the difference in BNP level in the presence (123 (13) pmol/L, n = 43) or absence (24 (1.5) pmol/L, n = 80) of heart failure. Using two way analysis of variance, no further improvement in discrimination was found when chest radiographs were used together with the BNP data. CONCLUSION: Rapid BNP assays are practicable and provide accurate information on cardiac status-superior to chest radiographs in many cases-early in the course of the patient's presentation with acute dyspnoea.

Acute Disease↗

PubMed1996

National Asthma Education and Prevention Program working group report on the financing of asthma care.

The financing of asthma care is the third topic of the National Asthma Education and Prevention Program Task Force Report on the Cost Effectiveness, Quality of Care, and Financing of Asthma Care. This working group explored the effects of financing on access to services, treatment of asthma, and potential health outcomes. Over the course of a year, the working group collected and analyzed information pertaining to the various types of public and private health care financing mechanisms, including both insurance-based and non-insurance-based issues. The group examined the published literature and gathered information from four public hearings conducted across the nation. The result of this synthesis of information on health care financing and asthma care is a set of 12 recommendations that seek to improve the financing of asthma care.

Asthma↗

PubMed1996

A review of physician-assisted suicide: where do you stand?

This article is intended to promote thought and discussion among nurses on the issue of physician-assisted suicide. A case study is presented to highlight some of the issues involved. A review of the literature presents medical and nursing views. The Netherlands' experience is summarized, with attention to the historical development and acceptance of assisted suicide and euthanasia in Dutch society. A review of current U.S. legal challenges follows, including decisions in Washington and New York in March and April 1996. The reader is asked to consider the ramifications of physician-assisted suicide and whether it should be an end-of-life choice.

Aged↗

PubMed1996

Recent findings on preventable hospitalizations.

Disparities in health outcomes for low-income populations as documented by rates of preventable hospital admission remains large in the United States, even with the moderate expansion of Medicaid and efforts at the state and local levels to improve primary care services that began in the mid-1980s. These differences in outcome for rich and poor are not an isolated phenomenon of a few old and decaying Northeast urban centers but are documented in a broad range of urban areas. Much smaller differences are found in urban areas in Ontario, where universal coverage may help to reduce barriers to care.

Ambulatory Care↗

PubMed1995

Preventable hospitalizations and access to health care.

OBJECTIVE: To examine whether the higher hospital admission rates for chronic medical conditions such as asthma, hypertension, congestive heart failure, chronic obstructive pulmonary disease, and diabetes in low-income communities resulted from community differences in access to care, prevalence of the diseases, propensity to seek care, or physician admitting style. DESIGN: Analysis of California hospital discharge data. We calculated the hospitalization rates for these five chronic conditions for the 250 ZIP code clusters that define urban California. We performed a random-digit telephone survey among adults residing in a random sample of 41 of these urban ZIP code clusters stratified by admission rates and a mailed survey of generalist and emergency physicians who practiced in the same 41 areas. SETTING: Community based. PARTICIPANTS: A total of 6674 English- and Spanish-speaking adults aged 18 through 64 years residing in the 41 areas were asked about their access to care, their chronic medical conditions, and their propensity to seek health care. Physician admitting style was measured with written clinical vignettes among 723 generalist and emergency physicians practicing in the same communities. MAIN OUTCOME MEASURES: We compared respondents' reports of access to medical care in an area with the area's cumulative admission rate for these five chronic conditions. We then tested whether access to medical care remained independently associated with preventable hospitalization rates after controlling for the prevalence of the conditions, health care seeking, and physician practice style. RESULTS: Access to care was inversely associated with the hospitalization rates for the five chronic medical conditions (R2 = 0.50; P < .001). In a multivariate analysis that included a measure of access, the prevalence of conditions, health care seeking, and physician practice style to predict cumulative hospitalization rates for chronic medical conditions, both self-rated access to care (P < .002) and the prevalence of the conditions (P < .03) remained independent predictors. CONCLUSION: Communities where people perceive poor access to medical care have higher rates of hospitalization for chronic diseases. Improving access to care is more likely than changing patients' propensity to seek health care or eliminating variation in physician practice style to reduce hospitalization rates for chronic conditions.

Adult↗

PubMed1995

The porous-coated anatomic (PCA) total hip arthroplasty: a review of 73 uncemented cases with 2-year follow up.

A total of 73 hips in 62 patients who underwent non-cemented total hip arthroplasties (THA) with porous-coated anatomic (PCA, Howmedica) prostheses have been reviewed. A complete evaluation including preoperative and postoperative Harris hip scores (HHSs), a complete radiographic study, and complication determination has been completed with greater than 2-year follow up. Diagnoses included osteoarthritis (74.0%), rheumatoid arthritis (4.1%), avascular necrosis (15.1%), and posttraumatic arthritis following fracture (6.8%). The complication rate was 10.9% (8 complications/73 arthroplasties); 20 patients (35.6%) received bilateral implants. The mean preoperative HHS for the entire group was 38.7, and the mean postoperative score, irrespective of postoperative time, was 93.6. Key findings regarding the consecutive radiographic review of each arthroplasty included: 9.6% lucencies, 43.8% stress shielding, stable fibrous ingrowth in 74.0%, tip sclerosis in 19.2%, and cortical widening in 4.1%. The finding of loose beads from the pore ingrowth area of the prosthesis was minimal (7 beads in 6 patients). These results demonstrate the efficacy of the PCA prosthesis.

Activities of Daily Living↗

PubMed1994

Plasma brain natriuretic peptide in assessment of acute dyspnoea.

Recognition of heart failure (HF) may be difficult in patients presenting with acute dyspnoea, particularly in the presence of chronic airways obstruction. Since increased secretion of the cardiac hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) occurs early in the course of HF, we have assessed the value of measuring these hormones in plasma in the diagnosis of suspected HF in 52 elderly patients presenting with acute dyspnoea, and compared values with left-ventricular ejection fraction (LVEF), a standard measure of left-ventricular function, by radionuclide angiography. Patients were enrolled prospectively. On the basis of clinical findings, conventional tests, and response to specific treatment, 20 of the 52 patients were classified as having primary lung disorder (PLD), 12 as HF alone, and 20 as HF with underlying PLD (HF/PLD). Compared with findings in PLD patients, LVEF was significantly depressed in HF and HF/PLD patients (p < 0.001), whereas both plasma ANP and BNP were significantly increased (p < 0.001). Admission plasma BNP concentration more accurately reflected the final diagnosis of HF (93% sensitivity and 90% specificity when BNP > or = 22 pmol/L) than LVEF or plasma ANP concentration. When all patients were considered together, there were strong negative correlations between LVEF and log BNP (r = -0.7, p < 0.001) and log ANP (r = -0.59, p < 0.001). Our finding that plasma BNP is raised in dyspnoeic patients with HF but not in acutely breathless patients with PLD, suggests that rapid BNP assays may assist in the diagnosis of patients with acute dyspnoea.

Acute Disease↗

PubMed1994

Concentration recovery for SPECT CNS dopamine-receptor studies for monkeys.

Most commercial SPECT scanners do not properly compensate for scattering and partial volume effects, which severely impacts the quantitation of clinical and research SPECT studies, especially in CNS dopamine studies. Hence, in this paper, a brain phantom containing a monkey skull was used to calibrate a Picker Prism 3000 SPECT camera for quantitative studies of 123I and 99mTc-labeled radiopharmaceuticals. In the calibration study, two small vials representing basal ganglia were inserted into a skull phantom. A series of images were taken with different concentration ratios between the basal ganglia and the other brain compartments to simulate the dynamic imaging study of the dopamine D2 receptor in a monkey brain. Based on this calibration, a simple method is proposed for count correction in the region of interest (ROI). This technique is superior to using a single calibration factor from a cylindrical uniform activity phantom since it can compensate for both the partial volume effect and the dynamically changing effect of scattering. A significant difference between the true and measured values was observed in the correction factors (by a factor as much as 3). Furthermore, a cylindrical phantom, approximately the size of a monkey's head and containing the same basal ganglia inserts, was used to investigate the feasibility of using a cylindrical phantom with the proposed correction method. The results indicate that it is feasible to use a cylindrical phantom for the case where the activity inside the brain cavity and the activity in the surrounding tissue are similar.

Animals↗

PubMed1993

Dicarboxylate diamide dimercaptide (N2S2) technetium-99m complexes: synthesis and biological evaluation as potential renal radiopharmaceuticals.

Novel diamide dimercaptide (N2S2) ligands 4, 5, and 8 have been synthesized and evaluated as potential renal radiopharmaceuticals. The target compounds were prepared in modest overall yields of 22%, 19%, and 20%, respectively, using readily available starting materials. Following in situ deprotection, 99mTc complexes of high radiochemical purity were obtained in excellent yield and were found to be stable for up to 6 h. The 99Tc complex of ligand 8 was isolated as the AsPh4 salt. The X-ray crystallographic data for [99TcO(8)]AsPh4 (space group P2(1)/n: Z = 4, a = 9.342(3) A; b = 18.594(5) A; c = 18.417(7) A; beta, deg = 90.61(3); V, A3 = 3199.1(20)) show that the Tc is bound to both thiolate sulfur atoms and to two deprotonated amide nitrogen atoms. The coordination geometry about the Tc is square-pyramidal with an -yl oxygen atom in the apical position. The Tc-N bond distances (2.002(12) and 1.984(12) A), the Tc-S bond distances (2.300(5) and 2.286(5) A), and the Tc-O bond distance (1.667(11) A) are in good agreement with bond lengths reported for similar complexes. The carboxylate groups are not bonded to the Tc atom in the solid state, nor in CDCl3 solution, as evidenced by X-ray crystal data and solution NMR data, respectively. In the solid state, [99TcO(8)]AsPh4 is monoanionic, therefore, at physiological pH, [99mTcO(8)] is presumably trianionic. Biodistribution studies performed in rats with the 99mTc complexes revealed slow blood clearance and high muscle uptake for these agents. Modest hepatobiliary excretion was observed, and low quantities of the complexes were found in the heart, lungs, and spleen after 1 h. The urinary excretion of the 99mTc complexes of ligands 4, 5, and 8 was found to be slow when compared to the excretion of [131I]OIH in rats (22%, 22%, and 32% vs 85-86%, respectively). Protein binding of 99mTc complexes of ligands 4, 5, and 8 in both rat and monkey plasma was found to be similar to MAG3. While the synthetic schemes reported here supply facile routes to novel N2S2 ligands, biodistribution studies of the 99mTc complexes performed on rats revealed slow renal excretion rates, accompanied by slow blood clearance and high uptake in muscle tissue. Preliminary planar imaging studies in monkeys also revealed slow renal excretion for these agents. The 99mTc complexes evaluated here are poor candidates as renal radiopharmaceuticals.

Animals↗

PubMed1993

Fluorinated and iodinated dopamine agents: D2 imaging agents for PET and SPECT.

A novel series of dual-labeling D2 dopamine agents (labeled with either 18F or 123I for PET or SPECT imaging, respectively) was investigated. Two desired fluorinated and iodinated dopamine agents, FIDA1, (S)-(-)-2-(2-fluoroethoxy)-5-iodo-3-methoxy-N-[(1-ethyl-2- pyrrolidinyl)methyl]-benzamide, and FIDA2, (R)-(+)-2,3-dimethoxy-5-iodo-N-[(1-(4'-fluorobenzyl)-2- pyrrolidinyl)-methyl]benzamide, were synthesized. Both compounds displayed high affinity to the D2 receptor of rat striatal membrane preparations (Kd = 0.13 and 0.02 nM for FIDA1 and FIDA2, respectively). The biodistribution study in rats exhibited high localization in the striata of the brain with the striatum/cerebellum ratio reaching 29.3 and 13.1 at 1 h post iv injection for FIDA1 and FIDA2, respectively. Imaging studies with [18F]- and [123I]FIDA2 in monkeys, with PET and SPECT, respectively, showed comparable high selective striatal uptake. These results suggest that they are potentially useful D2 dopamine receptor imaging agents for PET and SPECT.

Animals↗

PubMed1993

Impact of socioeconomic status on hospital use in New York City.

This DataWatch examines the potential impact of socioeconomic differences on rates of hospitalization, based on patterns of hospital use in New York City in 1988. The research suggests that lack of timely and effective outpatient care may lead to higher hospitalization rates in low-income areas. For certain conditions identified as ambulatory care sensitive, hospitalization rates were higher in low-income areas than they were in higher-income areas where appropriate outpatient care was more readily available. Further study is needed to determine the relative impact of various economic, structural, and cultural factors that affect access to care.

Adolescent↗

PubMed1992

Improved stenosis geometry by quantitative coronary arteriography after vigorous risk factor modification.

This study is a randomized, controlled, blinded, arteriographic trial to determine the effects of a low-cholesterol, low-fat, vegetarian diet, stress management and moderate aerobic exercise on geometric dimensions, shape and fluid dynamic characteristics of coronary artery stenoses in humans. Complex changes of different primary stenosis dimensions in opposite directions or to different degrees cause stenosis shape change with profound effects on fluid dynamic severity, not accounted for by simple percent narrowing. Accordingly, all stenosis dimensions were analyzed, including proximal, minimal, distal diameter, integrated length, exit angles and exit effects, determining stenosis shape and a single integrated measure of stenosis severity, stenosis flow reserve reflecting functional severity. In the control group, complex shape change and a stenosis-molding characteristic of statistically significant progressing severity occurred with worsening of stenosis flow reserve. In the treated group, complex shape change and stenosis molding characteristic of significant regressing severity was observed with improved stenosis flow reserve, thereby documenting the multidimensional characteristics of regressing coronary artery disease in humans.

Adult↗

PubMed1992

4-Iodotomoxetine: a novel ligand for serotonin uptake sites.

The tomoxetine analog, R-4-iodotomoxetine, binds in vitro to a single site of rat cortical membranes with high affinity (Kd = 0.03 +/- 0.01 nM, n = 4) and can be blocked by a selective serotonin reuptake site inhibitor, paroxetine. The [125I]R-4-iodotomoxetine binding at equilibrium is saturable and is temperature- and Na(+)-dependent. The number of specific [125I]R-4-iodotomoxetine binding sites (Bmax = 356 +/- 20 fmol/mg protein) is similar to that of [3H]citalopram (329 +/- 30 fmol/mg protein), a known serotonin uptake inhibitor. The binding of [125I]R-4-iodotomoxetine is selectively inhibited by several serotonin uptake blockers, and a good correlation is demonstrated between the potency of various drugs to inhibit in vitro binding of [125I]R-4-iodotomoxetine and [3H]citalopram. In addition, lesions performed with the neurotoxin p-chloroamphetamine, which destroys monoamine neurons, including serotonergic neuronal system, result in a 90% reduction of [125I]R-4-iodotomoxetine binding when compared to sham controls. These results indicate that the binding sites labeled by [125I]R-4-iodotomoxetine are associated with the neuronal serotonin uptake sites. However, the in vivo and ex vivo results do not show regional localization corresponding to the distribution of serotonin uptake sites. The nonspecific uptake may be related to this compound's high lipophilicity (octanol-buffer partition coefficient = 1100 - 1400 at pH 7). Although the in vivo properties of [125I]R-4-iodotomoxetine make it an unlikely candidate for mapping serotonin uptake sites with SPECT, the high affinity and selectivity should make it a useful tool for in vitro studies of the serotonin uptake sites.

Animals↗

PubMed1992

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane: potential radiotracer for mapping central cholinergic innervation in vitro.

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane, 5 (4-HIPP), was synthesized and evaluated as a simple vesamicol-like radiotracer for mapping cholinergic pathways in the brain. Both enantiomers of 5 exhibit significant accumulation (approx. 2% of injected dose) and prolonged retention (t1/2 greater than 3 h) within the rat brain. The accumulation of radioiodinated 5 in the rat brain was reduced by up to 70% in the presence of vesamicol and its analogs. The levorotary isomer (-)-4-[123I]HIPP exhibits significant accumulation in the monkey brain, with a half-life of about 9 h. Radioiodinated 5 may therefore be a useful tool for studying cholinergic pathways in the brain.

Animals↗

PubMed1991

Preparation, radiolabeling and biodistribution of a new class of bisaminothiol (BAT) ligands as possible imaging agents.

In developing new ligands as potential brain and heart perfusion imaging agents two ligands based upon N2S2 donor atoms with the biphenyl backbone were synthesized. Biphenyl-2,2'-bis(N-1-amino-2-methyl-propane-2-thiol) (BP-BAT-TM) and biphenyl-2,2'-bis(N-1-amino-2-ethyl-butane-2-thiol) (BP-BAT-TE) form stable, neutral and lipid soluble complexes with [99mTc]pertechnetate in the presence of tin(II) tartarate as a reducing agent. The [99mTc]BP-BAT-TM complex penetrates the blood-brain barrier following i.v. injection into rats. Washout from the brain is fast, indicating no retention. The biodistribution of [99mTc]BP-BAT-TE in rats showed an initial heart uptake (0.8%/organ, at 2 min) and a slow washout (0.74% at 15 min). No brain uptake was found (0.05%). Significant uptake and retention in liver was observed. An imaging study of [99mTc]BP-BAT-TE in a monkey showed no brain uptake and a clear indication of liver uptake and gall bladder clearance. These results indicate that this ligand system may be suitable as the basic core structure for the development of new imaging agents. Further studies with structural variations in the biphenyl backbone are warranted to develop new 99mTc imaging agents for clinical applications.

Animals↗

PubMed1990

Pargyline-sensitive selective accumulation of a radiolabeled MPTP analog in the primate cerebral cortex and basal ganglia.

The distribution of radioiodinated N-methyl-4-(4-hydroxy-3-iodobenzyl)-1,2,3,6-tetrahydropyridine (MHTP), an analog of the reportedly nontoxic N-methyl-4-benzyl-1,2,3,6-tetrahydropyridine, (4-homo-MPTP), has been studied in the primate. [123I]MHTP-derived radioactivity exhibited a progressive accumulation and prolonged retention within the primate eye. Following iv injection, [123I]MHTP rapidly accumulated within the primate brain and was subsequently oxidized to a radiolabeled metabolite. The half-life of [123I]MHTP-derived radioactivity within the primate brain was 50 min. The highest concentrations of radioactivity were found in the caudate-putamen and the frontal, temporal and cingulate cortices; the substantia nigra and inferior olivary nucleus were labeled with medium intensity. Very low concentrations of radiolabel were detected in the cerebellum and white matter. Selective accumulation of [125I]MHTP-derived radioactivity within these structures was blocked by pretreatment with pargyline, suggesting that monoamine oxidase B is involved in the bioactivation of radioiodinated MHTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1990

Speech characteristics and coronary heart disease incidence in the multiple risk factor intervention trial.

To assess whether speech characteristics descriptive of Type A behavior were related to coronary heart disease (CHD) incidence in the Multiple Risk Factor Intervention Trial, we scored voice emphasis, speed of speaking, latency of answering, and answer content from 577 audiotaped structured interviews in a case-control design which included all 193 individuals who incurred CHD during the 7-year follow-up. These were matched with 384 CHD-free controls. Multivariate analyses showed that subjects' voice emphasis [relative risk ratio (RR) = 1.25, p = .02] and latency of answering (RR = .78, p = .02) were significantly associated with CHD incidence when controlled for baseline levels of diastolic blood pressure, serum cholesterol, and cigarette smoking.

Adult↗

PubMed1990

Synthesis and characterization of iodobenzamide analogues: potential D-2 dopamine receptor imaging agents.

(S)-N-[(1-Ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-3-iodo-6- methoxybenzamide ([123I]IBZM) is a central nervous system (CNS) D-2 dopamine receptor imaging agent. In order to investigate the versatility of this parent structure in specific dopamine receptor localization and the potential for developing new dopamine receptor imaging agents, a series of new iodinated benzamides with fused ring systems, naphthalene (INAP) and benzofuran (IBF), was synthesized and radiolabeled, and the in vivo and in vitro biological properties were characterized. The best analogue of IBZM is IBF (21). The specific binding of [125I]IBF (21) with rat striatal tissue preparation was found to be saturable and displayed a Kd of 0.106 +/- 0.015 nM. Competition data of various receptor ligands for [125I]IBF (21) binding show the following rank order of potency: spiperone greater than IBF (21) greater than IBZM greater than (+)-butaclamol greater than (+/-)-ADTN,6,7 greater than ketanserin greater than SCH-23390 much greater than propranolol. The in vivo biodistribution results confirm that [125I]IBF (21) concentrated in the striatal area after iv injection into rats. The study demonstrates that [123I]IBF (21) is a potential agent for imaging CNS D-2 dopamine receptors.

Animals↗