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T Riley

Publications and source records attributed to T Riley.

At least 19 recordsLinked to original sources

Defining the drug incorporation properties of PLA-PEG nanoparticles.

The drug incorporation and physicochemical properties of PLA-PEG micellar like nanoparticles were examined in this study using a model water soluble drug, procaine hydrochloride. Procaine hydrochloride was incorporated into nanoparticles made from a series of PLA-PEG copolymers with a fixed PEG block (5 kDa) and a varying PLA segment (3-110 kDa). The diameter of the PLA-nanoparticles increased from 27.7 to 174.6 nm, with an increase in the PLA molecular weight. However, drug incorporation efficiency remained similar throughout the series. Incorporation of drug into the smaller PLA-PEG nanoparticles made from 3:5, 15:5 and 30:5 copolymers did not influence the particle size, while an increase was observed for the larger systems comprising 75:5 and 110:5 copolymers. An increase in drug content for PLA-PEG 30:5 nanoparticles was achieved by increasing the theoretical loading (quantity of initially present drug). The size of these nanoparticles remained unchanged with the increasing drug content, supporting the proposed micellar type structure of the PLA-PEG 30:5 nanoparticles. The morphology of these systems remained unchanged both at low and high theoretical drug loadings. Formulation variables, such as an increase in the aqueous phase pH, replacement with the base form of the drug and inclusion of lauric acid in the formulation did not improve the incorporation efficiency of drug into PLA-PEG 30:5 nanoparticles. While poly(aspartic acid) as a complexation agent did not improve the drug incorporation efficiency of procaine hydrochloride, it did so for another water soluble drug diminazene aceturate. This may be attributed to a stronger interaction of diminazene aceturate with poly(aspartic acid) relative to procaine hydrochloride, as confirmed by thermodynamic analysis of isothermal titration calorimetric data. The drug incorporation and physicochemical characterisation data obtained in this study may be relevant in optimising the drug incorporation and delivery properties of these potential drug targeting carriers.

Anesthetics, Local↗

Invasive Streptococcus pneumoniae in Perth teaching hospitals, 1990 to 1994.

Streptococcus pneumoniae causes pneumonia, otitis media and meningitis. Reports of penicillin resistance and the development of vaccines highlight the need for baseline information about pneumococcal disease in Australia. We surveyed Perth teaching hospital laboratory records for the period 1990 to 1994 for isolates of S. pneumoniae recovered from normally sterile sites, and obtained isolate and patient demographic information. Highest rates of invasive disease were found at the extremes of age and were associated with Aboriginality. Isolates were rarely penicillin resistant. Surveillance of invasive pneumococcal disease will be of importance in monitoring the emergence of penicillin resistance and the impact of conjugate vaccines.

Adolescent↗

Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium.

Mature adult parenchymal hepatocytes, typically of restricted capacity to proliferate in culture, can now enter into clonal growth under the influence of hepatocyte growth factor (scatter factor) (HGF/SF), epidermal growth factor (EGF), and transforming growth factor alpha (TGFalpha) in the presence of a new chemically defined medium (HGM). The expanding populations of hepatocytes lose expression of hepatocyte specific genes (albumin, cytochrome P450 IIB1), acquire expression of markers expressed by bile duct epithelium (cytokeratin 19), produce TGFalpha and acidic FGF and assume a very simplified morphologic phenotype by electron microscopy. A major change associated with this transition is the decrease in ratio between transcription factors C/EBPalpha and C/EBPbeta, as well as the emergence in the proliferating hepatocytes of transcription factors AP1, NFkappaB. The liver associated transcription factors HNFI, HNF3, and HNF4 are preserved throughout this process. After population expansion and clonal growth, the proliferating hepatocytes can return to mature hepatocyte phenotype in the presence of EHS gel (Matrigel). This includes complete restoration of electron microscopic structure and albumin expression. The hepatocyte cultures however can instead be induced to form acinar/ductular structures akin to bile ductules (in the presence of HGF/SF and type I collagen). These transformations affect the entire population of the hepatocytes and occur even when DNA synthesis is inhibited. Similar acinar/ductular structures are seen in embryonic liver when HGF/SF and its receptor are expressed at high levels. These findings strongly support the hypothesis that mature hepatocytes can function as or be a source of bipotential facultative hepatic stem cells (hepatoblasts). These studies also provide evidence for the growth factor and matrix signals that govern these complex phenotypic transitions of facultative stem cells which are crucial for recovery from acute and chronic liver injury.

Adult↗

The Arizona Long Term Care System.

The Arizona Long Term Care System (ALTCS) is the first statewide capitated managed care system that combines Medicaid acute and long-term-care services. ALTCS provides institutional, residential, and in-home services to elderly and disabled Medicaid recipients who meet the criteria for placement in a nursing facility. The capitation payment structure creates incentives for contractors to serve members in their own homes or in residential settings rather than in nursing facilities. Regular monitoring, case management oversight, and member satisfaction surveys assure that services are provided when needed in a cost-effective manner. As a result of the success of the 6-year-old program, a cap on the number of members who can receive home and community-based services, imposed at the program's inception in 1989 at 5%, has been increased to 40% in 1995. Despite this expansion of home and community care, an independent evaluation found that ALTCS expenditures are 17% lower than would have been incurred in a fee-for-service system.

Aged↗

Antiemetic efficacy of a droperidol-morphine combination in patient-controlled analgesia.

STUDY OBJECTIVES: To evaluate the antiemetic effectiveness and side effects of adding low-dose droperidol to morphine delivered via a patient-controlled analgesia (PCA) device. DESIGN: Randomized, double-blind, clinical study. SETTING: University-affiliated women's hospital. PATIENTS: 60 healthy women, 18 to 60 years of age, who underwent total abdominal hysterectomy with a standardized anesthetic regime. INTERVENTIONS: After surgery, the control group (n = 20) had access via PCA to two cartridges, each containing morphine 1 mg/ml and saline 1 ml. The two treated groups (n = 20 each) had access via PCA to either droperidol 0.5 mg or droperidol 1 mg added to two cartridges containing morphine 1 mg/ml. MEASUREMENTS AND MAIN RESULTS: Preoperative data, including each patient's history of nausea and vomiting with and without previous anesthesia, motion sickness, smoking, and alcohol intake, and date of her last menstrual period, were obtained. All patients received a standardized anesthetic with droperidol 0.5 mg given at closure of the peritoneum. Among those patients who received droperidol added to morphine for their postoperative analgesic regimen, fewer required rescue antiemetic medication (p < 0.05, test of trend in proportions), and they had a lower incidence of vomiting (p < 0.05, test of trend in proportions), as well as a decrease in the number of times a rescue antiemetic was needed during the 24-hour postoperative period (linear trend, p = 0.013). CONCLUSIONS: An intermittent intake of low-dose droperidol with morphine given via a PCA delivery system in two treatment groups gave evidence for a dose-response relation between the amount of droperidol added and the proportion of patients needing a rescue antiemetic. The same result applied to the proportion of patients having an emetic episode and the number of times a rescue antiemetic had to be administered. There was no evidence that the low dose of droperidol added to morphine delivered via a PCA device increased unwanted side effects.

Adolescent↗

State health reform and the role of 1115 waivers.

This article summarizes the status of State health reform and includes a table of major initiatives undertaken by each State. The Health Care Financing Administration's (HCFA's) role in reviewing State waiver proposals is analyzed, and the author examines why States are likely to continue to seek section 1115 waivers, absent Federal health care reform. The often conflicting roles and responsibilities of Federal and State policy-makers in health reform are explored.

Centers for Medicare and Medicaid Services, U.S.↗

Alpha 2A-adrenergic receptors are present in lower brainstem catecholaminergic and serotonergic neurons innervating spinal cord.

A subtype-specific polyclonal antibody was used for the immunohistochemical detection of alpha 2A-adrenergic receptors (alpha 2A-ARs) in the rat lower brainstem (medulla and pons). Using dual-label fluorescence histochemistry, punctate alpha 2A-AR-like immunoreactivity (alpha 2A-AR-LIR) was identified in noradrenergic, adrenergic, and serotonergic neurons of the pontomedullary region. Confocal microscopic examination of material simultaneously labeled for TH-LIR and alpha 2A-LIR revealed that the clusters of alpha 2A-LIR were located intracellularly. Lower medullary neurons with spinal projections to segment T3 were retrogradely labeled using FITC-conjugated microbeads and the material was processed for simultaneous detection of alpha 2A-LIR and either TH-LIR or 5-HT-LIR. Using this triple-label approach, we found that virtually all medullary serotonergic cells (raphe pallidus, raphe obscurus and parapyramidal area) including those with identified spinal projections contain punctate alpha 2A-AR-LIR. In contrast, fewer than 10% of dorsal raphe serotonergic cells examined for comparison were immunoreactive. The triple labeling approach also indicated that more than 95% of the TH-immunoreactive cells of the dorsal and ventrolateral medulla, including those with demonstrable spinal projections (A5 noradrenergic and C1/C3 adrenergic) had detectable amounts of alpha 2A-AR-LIR. The presence of alpha 2A-ARs in a large fraction of bulbospinal pre-sympathetic neurons (noradrenergic A5, adrenergic C1 and C3 and serotonergic raphe cells) could explain the powerful and relatively selective effect of clonidine and other centrally acting alpha 2A-AR agonists on sympathetic efferent activity and hypertension.

Animals↗

Health reform: what to expect from the coming debate. Interview by Jeannie Mankelker, Dan Wise, and Steven Findlay.

Health care reform is in limbo as 1994 draws to a close. Last month's Republican sweep puts the issue in a starkly new political environment. The new Congressional leadership said last month it will put forth a reform plan in 1995. Also, the Clinton administration is working on a scaled-back proposal. To get an idea of what might happen next year, we invited 20 informed persons to give us their opinions and to tell us what action they'd prefer. Because of B&H's production schedule, the interviews took place before the election. We don't think that diminishes their insights and analyses.

Forecasting↗

Immunohistochemical localization of alpha 2A-adrenergic receptors in catecholaminergic and other brainstem neurons in the rat.

alpha 2-Adrenergic receptors mediate a large portion of the known inhibitory effects of catecholamines on central and peripheral neurons. Molecular cloning studies have established the identity of three alpha 2-adrenergic receptor genes from several species that encode the A, B and C subtypes of the receptor. The rat alpha 2A-adrenergic receptor, as defined by sequence similarity, is the orthologue of the human alpha 2A-adrenergic receptor. In this paper, we report the development of rabbit antisera directed against a portion of the third intracellular loop of the rat alpha 2A-adrenergic receptor and the histochemical localization of alpha 2A-adrenergic receptor-like immunoreactive material in the brainstem and spinal cord of the adult rat. Our antisera detected alpha 2A-adrenergic receptor-specific punctate staining associated with neuronal perikarya. alpha 2A-adrenergic receptor-like immunoreactivity was widely, but heterogeneously, distributed in the brainstem and spinal cord, predominantly in areas involved in the control of autonomic function. Double labelling with antisera to tyrosine hydroxylase or phenylethanolamine-N-methyl-transferase revealed that alpha 2A-adrenergic receptor-like immunoreactivity is present in most, perhaps all, noradrenergic and adrenergic cells of the brainstem. alpha 2A-Adrenergic receptor-like immunoreactivity was detected in a small percentage of the dopaminergic cells of the A9 and A10 groups. This study provides the first description of the specific immunohistochemical localization of alpha 2A-adrenergic receptors using a subtype-specific polyclonal antibody. The results support the view that alpha 2-adrenergic receptors are involved in central cardiovascular control and suggest that the catecholaminergic autoreceptors of central noradrenergic and adrenergic neurons are the A subtype of the alpha 2-adrenergic receptors.

Animals↗

Laws of war.

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Military Medicine↗