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Biomedical subjects

E C Smith

Publications and source records attributed to E C Smith.

At least 37 records · Page 2Linked to original sources
PubMed1995

Role of cocaine in end-stage renal disease in some hypertensive African Americans.

During a period of 1 year we observed 12 African American patients who had smoked or sniffed cocaine for several years and presented to inner city hospitals with accelerated hypertension and renal insufficiency. Ten required maintenance dialysis; 1 recovered partially after a brief period of dialysis, and 1 had moderate renal insufficiency. In the absence of striking proteinuria, cardiomegaly or renal shrinkage, the probable diagnosis in most of the patients was primary accelerated hypertension. The clinical history suggested that the habitual use of cocaine had worsened the hypertension, made it more difficult to control or triggered an accelerated phase resulting in renal shutdown. At a time when billions of dollars are being spent on the treatment of end-stage renal disease, the harmful role of cocaine in susceptible individuals requires due attention.

Adult↗
PubMed1995

Comparison of twenty three nebulizer/compressor combinations for domiciliary use.

We have assessed the physical and dynamic characteristics of 23 home jet nebulizer/compressor combinations currently available in the UK and Europe. The combinations were evaluated in terms of pressure-flow characteristics, aerosol mass distribution, volume output, electrical costs, and sound level. In addition, we determined the effect of nebulizer fill volume on aerosol mass distribution and volume output. One nebulizer was used with six different compressors, and four compressors were tested with three different nebulizers. The pressure-flow relationships showed a wide variation between models, as did flow-rate at the nebulizer (range 3.0-8.0 L.min-1). The mean +/- SD volume nebulized after 10 min using an initial fill volume of 2.5 and 5.0 mL was 46 +/- 9 and 34 +/- 12%, respectively. The mass median aerodynamic diameter (MMAD) over a 5 min nebulization ranged 2.6 to 10.2 microns. Nine of the nebulizations produced an MMAD of less than 5 microns at both fill volumes. Changing nebulizer/compressor combinations affected flow rate, MMAD and volume output. Sound levels varied between models. Running costs were low, with all using less than 74 kilowatt hours of energy per year. We conclude that there is a wide variation in performance of nebulizer/compressor combinations for use with nebulized bronchodilators. Correct matching of the nebulizer/compressor is seen to be important to ensure optimum performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

Intra-articular injections of 750 kD hyaluronan in the treatment of osteoarthritis: a randomised single centre double-blind placebo-controlled trial of 91 patients demonstrating lack of efficacy.

OBJECTIVE: To determine the safety and efficacy of intra-articular injections of hyaluronan in the treatment of osteoarthritis of the knee. METHODS: A randomised double-blind placebo-controlled trial was carried out on 91 patients with radiologically confirmed osteoarthritis of the knee who were recruited from the outpatient clinics. RESULTS: It was found that weekly intraarticular injections of 20 mg of hyaluronan of M(r) = 750,000 (Hyalgan) in 2 ml of buffered saline performed no better than the inert vehicle alone over a five week period. The principal side effects of a transient increase in pain and swelling in the affected knee was observed in 47% of the treatment group compared with 22% of the placebo group. A few patients with radiologically mild disease treated with Hyalgan appeared to experience medium to long-term symptomatic improvement over matched placebo controls as judged by a delayed return to previous NSAID therapy or analgesia other than paracetamol. Patient numbers in the survival groups, however, were too small to be meaningful. CONCLUSION: It is concluded that intraarticular administration of this preparation of 750 kD hyaluronan offers no significant benefit over placebo during a five week treatment period, but incurs a significantly higher morbidity, and therefore has no place in the routine treatment of osteoarthritis.

Acetaminophen↗
PubMed1993

An investigation of the abnormal metabolic status of synovial fluid from patients with rheumatoid arthritis by high field proton nuclear magnetic resonance spectroscopy.

The 1H Hahn spin-echo NMR profiles of rheumatoid synovial fluids have been investigated and compared with those of matched serum samples. In addition to markedly elevated lactate and diminished glucose concentrations, inflammatory synovial fluids contained (i) substantially lower levels of NMR-detectable chylomicron-and very-low-density-lipoprotein-associated triacylglycerols which appear to have a shortened mean chain-length, and (ii) high concentrations of ketone bodies (predominantly 3-D-hydroxybutyrate), relative to those of corresponding paired serum samples. These observations confirm the abnormal metabolic status of the inflamed rheumatoid joint and provide evidence for an increased utilisation of lipids for fuel therein.

3-Hydroxybutyric Acid↗
PubMed1993

How do inhaled bronchodilators work?

1. Beta-agonists affect bronchodilation of the airways by their action on the bronchial smooth muscles. 2. Anticholinergic drugs affect bronchodilation of the airways by blocking the effect of acetylcholine and its bronchoconstrictor action. 3. Receptors are protein molecules found in cell membranes; they can selectively bind to messenger molecules and transduce a chemical signal into a response in a target cell.

Acetylcholine↗
PubMed1992

Synthesis and excitatory amino acid pharmacology of a series of heterocyclic-fused quinoxalinones and quinazolinones.

As part of our program aimed at the development of potent excitatory amino acid antagonists, we synthesized and evaluated a series of substituted 1,2,4-triazolo[4,3-a]quinoxalin-4(5H)-ones, 4, tetrazolo[1,5-a]quinoxalin-4(5H)-ones, 5, and pyrazolo[1,5-c]quinazolin-5(6H)-ones, 6, and an imidazo[1,2-a]quinoxalin-4(5H)-one, 7. In general, the same heterocycles which demonstrated the best affinity for the AMPA receptor also demonstrated the best affinity for the glycine site on the NMDA receptor complex. 1-Propyl-7,8-dichloro-1,2,4-triazolo[4,3-a]quinoxalin-4(5H)-one, 4d, was found to bind with the greatest affinity to the AMPA receptor with an IC50 of 0.83 microM and antagonized 40 microM AMPA-induced depolarization in the cortical slice preparation with an IC50 of 44 microM. 7,8-Dichloro-1,2,4-triazolo[4,3-a]quinoxalin-4(5H)-one, 4a, and 7,8-dichloroimidazo[1,2-a]quinoxalin-4(5H)-one, 7, possessed the best affinity for the glycine site with IC50 values of 0.63 and 1.26 microM, respectively. It is noteworthy that the SAR for the heterocyclic compounds did not directly parallel that of known quinoxalinediones (e.g. DNQX, 2, and DCQX, 15) at the AMPA receptor nor that of the kynurenic acids at the glycine site on the NMDA receptor complex.

Animals↗
PubMed1992

Inhibitors of blood platelet cAMP phosphodiesterase. 2. Structure-activity relationships associated with 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones substituted with functionalized side chains.

A series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives, substituted at the 7-position with functionalized side chains, was synthesized and evaluated as inhibitors of human blood platelet cAMP phosphodiesterase (PDE) as well as ADP- and collagen-induced platelet aggregation, in vitro. Structural modifications focused on variation of the side-chain terminus, side-chain length, and side-chain connecting atom. Functionality incorporated at the side-chain terminus included carboxylic acid, ester and amide, alcohol, acetate, nitrile, tetrazole, and phenyl sulfone moieties. cAMP PDE inhibitory potency varied and was dependent upon the side-chain terminus and its relationship with the heterocyclic nucleus. Methylation at N-1 or N-3 of the heterocycle diminished cAMP PDE inhibitory potency. Several representatives of this structural class demonstrated potent inhibition of ADP- and collagen-induced blood platelet aggregation and were half-maximally effective at low nanomolar concentrations. Amides 13d, 13f, 13h, 13k, 13m, and 13w are substantially more potent than relatively simply substituted compounds. However, platelet inhibitory properties did not always correlate with cAMP PDE inhibition across the series, probably due to variations in membrane permeability. Several compounds inhibited platelet aggregation measured ex vivo following oral administration to rats. Ester 11b, acid 12b, amide 13d, and sulfone 29c protected against thrombus formation in two different animal models following oral dosing and were found to be superior to anagrelide (2) and BMY 20844 (5). However, ester 11b and acid 12b demonstrated a unique pharmacological profile since they did not significantly affect hemodynamic parameters in dogs at doses 100-fold higher than that required for complete prevention of experimentally induced vessel occlusion in a dog model of thrombosis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Inhibitors of blood platelet cAMP phosphodiesterase. 3. 1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives with enhanced aqueous solubility.

Two series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives incorporating an additional site for acid salt formation were synthesized and evaluated as inhibitors of human blood platelet cAMP phosphodiesterase (PDE) and ADP-induced platelet aggregation. The objective of this study was to identify compounds that blended potent biological activity with a satisfactory level of aqueous solubility. From a series of 7-aminoimidazo[4,5-b]quinolin-2-ones, biological and physical properties were optimally combined in the 1-piperidinyl derivative 11c. However, this compound offered no significant advantage over earlier studied compounds as an antithrombotic agent in an animal model of small vessel thrombosis. A series of 7-alkoxy alkanoic piperazinamide derivatives, in which the additional basic nitrogen atom was remote from the heterocyclic nucleus and accommodated in a secondary binding region of the cAMP PDE enzyme, demonstrated greater intrinsic cAMP PDE inhibitory activity. Structural modifications of this series focused on variation of the piperazine substituent and side-chain length. The lipophilicity of the N-substituent influenced biological potency and aqueous solubility, with substituents of seven carbon atoms or less generally providing acceptable solubility properties. The N-(cyclohexylmethyl)piperazinamide 21h was identified from this series of compounds as a potent inhibitor of platelet cAMP PDE, IC50 = 0.4 nM, and ADP-induced platelet aggregation, IC50 = 0.51 microM after a 3-min exposure and 0.1 microM after a 15-min exposure of platelet-rich plasma to the drug. Evaluation of 21h and representative analogues in vivo using a rabbit model of small vessel thrombosis revealed significantly greater antithrombotic efficacy compared to that of previously studied compounds with similar intrinsic biological activity measured in vitro but inferior aqueous solubility.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Serum immunoreactive erythropoietin in patients with idiopathic aplastic and Fanconi's anaemias.

In patients with idiopathic aplastic anaemia (n = 34) and Fanconi's anaemia (n = 8), sampled once or on several occasions, serum erythropoietin (Epo) increased with increasing severity of anaemia with apparently similar rates of increase in each group. However, after adjustment for Hb, log Epo values for the Fanconi's anaemics tended to be greater than those for the idiopathic aplastic anaemics (P < 0.01). Erythropoietin concentrations in serum samples from patients with Fanconi's and idiopathic aplastic anaemias tended to be greater than in samples from patients with anaemias from protein energy malnutrition, myelodysplasia and iron deficiency. The results suggest that there is no deficiency of erythropoietin in Fanconi's and idiopathic aplastic anaemias and that if exogenous erythropoietin is of any benefit it would need to be administered in doses large enough to induce a significant increase in log Epo. Results of the study illustrate the need to take account of the assumptions which underlie interpretation of the statistical analysis. Use of erythropoietin values in place of log Epo gives misleading conclusions demonstrable as invalid as the conditions for normality of distribution of the data and homogeneity of variances were not satisfied.

Adolescent↗
PubMed1992

Inhibition of [3H]-MK801 binding and protection against NMDA-induced lethality in mice by a series of imipramine analogs.

A series of imipramine analogs were tested for inhibition of [3H]-MK801 binding and for their ability to protect against NMDA-induced lethality in mice. The structure-activity relationship (SAR) for the inhibition of [3H]-MK801 binding found primary amines on short linkers to be optimum. For protection against NMDA lethality, compounds containing an unsaturated link to a cyclic amine were the most potent analogs tested. Possible explanations for the lack of correlation observed are briefly discussed.

Animals↗
PubMed1992

A network model for improving access to food and nutrition data.

In this article we propose a network in which existing food composition and consumption databases are linked through a master database of complete and detailed food descriptions. The proposal arises from an analysis of the importance of food data, their descriptive and analytical nature, and their uses. Lack of detail and standardization in food description hinders the retrieval of food and nutrition data from various databases and the integration of such data. Standardized food descriptions can be developed and maintained in the master database, which can then serve as the interface to the many existing databases of analytical data (especially food composition data) and to databases containing data on food production, consumption, and effects, thereby linking these databases in a coordinated system, or network. The ability to link food-related databases by standardized food descriptions offers a powerful tool for scientists and practitioners in the field of food and nutrition.

Computer Communication Networks↗
PubMed1991

1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-ones--inhibitors of blood platelet cAMP phosphodiesterase and induced aggregation.

A series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives was synthesized and evaluated as inhibitors of cAMP hydrolysis by a crude human platelet phosphodiesterase preparation and as inhibitors of ADP- and collagen-induced aggregation of rabbit blood platelets. The parent structure 7a, demonstrated potent inhibitory activity that was enhanced by the introduction of alkyl, alkoxy, or halogen substituents at the 5-, 6-, 7-, and 8-positions. Methylation at N-1 or N-3 produced weaker inhibitors of cAMP PDE and platelet aggregation. 1,3,9,9a-Tetrahydro-2H-imidazo[4,5-b]quinolin-2-ones (6) were found to be equipotent with their fully oxidized congeners (7). On the basis of platelet inhibitory properties in vitro, efficacy at preventing thrombus formation in animal models of thrombosis, and a favorable hemodynamic profile, 1,3-dihydro-7,8-dimethyl-2H- imidazo[4,5-b]quinolin-2-one (7o, BMY 20844) was selected for advancement into toxicological evaluation and clinical trial. An efficient synthesis of 7o is described.

3',5'-Cyclic-AMP Phosphodiesterases↗