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Biomedical subjects

L H Smith

Publications and source records attributed to L H Smith.

At least 19 recordsLinked to original sources

Calcium oxalate dihydrate crystal growth.

Calcium oxalate dihydrate (COD), although thermodynamically unstable with respect to calcium oxalate monohydrate (COM), is more commonly seen in human urine. For the first time, a COD-seeded crystal growth assay has been developed. Seed crystals of COD were precipitated from filtered urine by the addition of ammonium oxalate and were stored dry and added to a supersaturated calcium oxalate solution to initiate an experiment. The growth rate in the COD-seeded system was 22 per cent of that for a COM-seeded system, for equivalent surface areas. Urine samples from normal subjects have similar inhibitory activity in the COD- and COM-seeded systems, as do pyrophosphate and heparin, which are known inhibitors of COM crystal growth. These results indicate that the technically simpler COM-seeded growth assay is suitable for measurement of inhibitors of calcium oxalate growth in urine.

Calcium Oxalate

Skin carcinogenicity of synthetic and natural petroleums.

In a series of three separate experiments mice were exposed to various concentrations of fossil liquids obtained from coal, oil shale or natural petroleum. All materials were capable of inducing squamous cell carcinoma, but potency differed substantially. Skin carcinogenicity was markedly greater for both coal or oil shale liquids than for natural petroleums. None of the syncrudes approached the skin carcinogenicity of a pure reference carcinogen, benzo(a)pyrene (BP). It is unlikely that determination of the concentration of an active compound in material applied to the test animal will allow meaningful comparison among the diverse agents of interest to the synthetic fuels industry. To better establish the relationship between actual tissue dose and surface concentration the authors are investigating various in vitro and biochemical measures of hydrocarbon-skin interaction to determine which, if any, could serve as a more definitive measure of surface dose. Results, using BP as a marker carcinogenic hydocarbon, suggest that carcinogenic crudes inhibit both BP metabolism in skin organ culture and the interaction of BP adducts with epidermal DNA, in vivo.

Animals

Thoracic neurolophomas.

Neural crest cells are unique. Few tissues found in the embryo are expressed with such diversity in adults. Cellular differentiation occurs simultaneously with widespread migration. Neural crest cell neoplasia results in some of the most common tumors clinically encountered. As a group, these tumors are called neurolophomas. This report describes the neural crest formation, the tissues normally derived from it, a classification of the neural crest tumors, and a review of such tumors as they arise in the thorax.

Adult

beta-Adrenergic blocking agents. 16. 1-(Acylaminomethyl-, ureidomethyl-, and ureidoethylphenoxy)-3-amino-2-propanols.

The synthesis of a series of 1-(acylaminomethyl-, ureidomethyl-, and ureidoethylphenoxy)-3-amino-2-propanols is described. The compounds were screened as beta-adrenergic receptor antagonists in cats and their partial agonist activity was evaluated in rats depleted of circulating catecholamines. Some of the compounds have a pharmacological profile similar to atenolol. Their structure-activity relationships are discussed.

Adrenergic beta-Antagonists

beta-Adrenergic blocking agents. 17. 1-Phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propanols.

The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized cats for their effects on an isoproterenol-induced tachycardia and depressor response. The structure-activity relationship shown by this series of compounds is related to that of known cardioselective analogues and a possible reason for their cardioselectivity is discussed.

Adrenergic beta-Antagonists

Epitaxial relationships in urolithiasis: the brushite-whewellite system.

1. Whewellite (calcium oxalate monohydrate) crystals were found to induce epitaxially the heterogeneous nucleation of brushite (calcium monohydrogen phosphate dihydrate) from its metastable supersaturated solution in approximately one-quarter of the time required for spontaneous precipitation in the absence of added nucleating agents. Scanning electron-microscope observation of the crystalline phase showed brushite crystals originating from the whewellite seed crystals. 2. Crystal growth, upon nucleation, proceeded rapidly, and the metastable solutions quickly approached saturation. 3. Brushite crystals also induced the precipitation of calcium oxalate crystals in about one-quarter of the time required for spontaneous precipitation; however, the rate of crystal growth was considerably slower. In support of the chemical data, scanning electron micrographs showed few crystals of calcium oxalate nucleated on the surface of the brushite seed. 4. The results provide some insight into the cause of stones containing calcium oxalate or calcium phosphate (or both), which form in the normally acid environment of human urine.

Calcium Phosphates

Clinical features and management of cystinuria.

Cystinuria is a complex hereditary disorder that affects both sexes with equal frequency and severity. Symptoms usually begin early (children and young adults) but may develop at any age. Stature is normal and there are no clinical nutritional abnormalities. The morbidity of cystine urolithiasis is considerable. Hyperuricemia is a frequent associated finding and is probably the result of multiple factors. No other abnormalities are consistently related to this disease. Treatment with adequate oral fluids to ensure a copious urine volume and with oral alkali to keep the urine alkaline is most successful when used prophylactically in the stone-free patient. However, dissolution of existing calculi is unlikely with this regimen alone. The addition of D-penicillamine often results in dissolution of stones and prevention of recurrent calculi in patients who have continued stone growth despite the use of oral fluids and alkali. Because toxic reactions with D-penicillamine are frequent and sometimes severe, this drug should be used only when necessary and then as an adjunct to rather than a substitute for increased oral fluids and alkali. Failure of treatment in spite of adequate therapy should alert the physician to the possibility of coexisting complicating problem.

Adolescent